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Novel NSAID–triptan drug effectively relieves migraine pain
, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.
In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.
Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.
“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.
The findings were presented at the American Headache Society’s 2021 annual meeting.
Acute treatments needed
For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.
The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.
Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.
In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.
The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.
The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.
Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
Reduced pain progression
Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).
Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).
The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).
In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).
AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).
The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.
“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
Improved adherence?
Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.
AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.
“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.
The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.
Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
Uncertain therapeutic advantage
Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.
“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.
It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.
In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.
For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.
Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.
“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.
“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.
The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.
A version of this article first appeared on Medscape.com.
, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.
In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.
Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.
“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.
The findings were presented at the American Headache Society’s 2021 annual meeting.
Acute treatments needed
For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.
The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.
Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.
In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.
The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.
The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.
Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
Reduced pain progression
Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).
Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).
The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).
In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).
AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).
The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.
“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
Improved adherence?
Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.
AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.
“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.
The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.
Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
Uncertain therapeutic advantage
Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.
“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.
It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.
In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.
For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.
Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.
“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.
“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.
The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.
A version of this article first appeared on Medscape.com.
, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.
In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.
Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.
“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.
The findings were presented at the American Headache Society’s 2021 annual meeting.
Acute treatments needed
For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.
The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.
Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.
In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.
The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.
The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.
Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
Reduced pain progression
Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).
Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).
The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).
In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).
AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).
The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.
“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
Improved adherence?
Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.
AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.
“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.
The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.
Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
Uncertain therapeutic advantage
Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.
“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.
It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.
In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.
For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.
Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.
“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.
“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.
The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.
A version of this article first appeared on Medscape.com.
From AHS 2021
COVID-19 vaccines are safe and effective for patients with migraine
according to a presentation at the American Headache Society’s 2021 annual meeting.
Amy Gelfand, MD, director of pediatric headache at University of California, San Francisco, reviewed common concerns migraine patients or their clinicians might have related any of the three vaccines, starting with a review of how the vaccines work – by targeting the spike protein of the SARS-CoV-2 virus.
“The vaccines induce response to that protein, but only that protein, so there’s no reason to think they’re going to cause the body to produce neutralizing antibodies against any of our migraine therapeutics,” Dr. Gelfand said. She added that the phase 3 clinical trials included participants from a wide range of ages and comorbidities, so there were likely many people in the trials who have migraine, though no subgroup analyses have been performed for this group or are likely to be performed.
Common questions
The two treatments people have the most questions about concerning the COVID-19 vaccine are onabotulinumtoxinA and CGRP pathway monoclonal antibodies (mAbs), likely because both of these are injections, as is the vaccine, Dr. Gelfand said. First, she reminded attendees that onabotulinumtoxinA is not a dermal filler, since some reports following administration of the Moderna vaccine suggested that some people with dermal fillers had swelling in those areas after vaccination.
In addition, “there’s no reason to think the onabotulinumtoxinA would influence our body’s immune response to any vaccine, so there’s no need to retime the onabotulinumtoxinA injections around COVID-19 vaccine administration,” Dr. Gelfand said.
Regarding mAbs, she acknowledged that some white blood cells have CGRP receptors, which may have a pro- or anti-inflammatory role, but clinical trials of mAbs did not show any evidence of being immunosuppressive or myelosuppressive.
“The monoclonal antibodies themselves have undergone engineering so that they are just going after their one target,” Dr. Gelfand said. “They’re not going to be expected to bind to anything else outside of their targets, so I don’t think there’s anything there to make us retime the monoclonal antibody administration relative to the COVID-19 vaccine.”
She did note that patients who choose to get mAbs injections in their arm instead of their thigh or abdomen may want to receive it in the opposite arm than they one they have gotten or will get the vaccine in since the vaccine can cause discomfort.
The other common question patients may have is whether taking any NSAIDs or acetaminophen before getting the COVID-19 vaccine will reduce their immune response to the vaccination. This concern arises because of past evidence showing that some infants tended to have lower immunologic responses when they received acetaminophen after their primary vaccines’ series, but the clinical significance of those reduced responses is not clear since they still had strong responses. Further, this effect was not seen with booster shots, suggesting it’s an age-dependent effect.
During the clinical trials of the AstraZeneca vaccine, several sites gave prophylactic paracetamol without any apparent detrimental effect on antibody response, Dr. Gelfand said. Further, the mRNA and adenovirus-vectored vaccines appear to induce antibodies far above what many believe is needed for protection.
“Even if there were a slight decrease, it’s not clear that that would have any kind of clinical significance for that person in terms of their level of protection against COVID-19,” she said. “Bottom line, it’s fine for patients to use either of these after administration of the COVID-19 vaccine.” The Centers for Disease Control and Prevention doesn’t recommend it prophylactically beforehand, but it’s fine to take it for a fever, aches or headache after getting the vaccine.
Migraine or vaccine reaction?
Dr. Gelfand then addressed whether it should affect physicians’ headache differential if seeing a patient who recently received an adenovirus-vectored vaccine, such as the Johnson & Johnson or AstraZeneca vaccines. The question relates to the discovery of a very rare potential adverse event from these vaccines: cerebral venous sinus thrombosis (CVST) with thrombocytopenia and thromboses in other major vessels, together called thrombosis thrombocytopenia syndrome (TTS). No TTS cases have been reported following mRNA vaccines.
TTS’s mechanism appears similar to autoimmune heparin-induced thrombocytopenia, where the body produces platelet-activating antibodies. TTS currently has three diagnostic criteria: new-onset thrombocytopenia (<150,000/microliter) without evidence of platelet clumping, venous or arterial thrombosis, and absence of prior exposure to heparin.
So far, TTS has been limited only to the vaccines that use an adenovirus vector. One male clinical trial participant experienced CVST with thrombocytopenia in Johnson & Johnson phase 3 trials, and 12 cases out of approximately 8 million Johnson & Johnson doses were reported to the Vaccine Adverse Event Reporting System between March 2 and April 21, 2021. Three TTS more cases followed these, resulting in 15 TTS events per 8 million doses.
In terms of clinical features, all 15 cases were females under age 60, mostly white, and all 11 who were tested were positive for the heparin-platelet factor 4 antibody test. TTS occurred 6-15 days after vaccination for these cases, and all but one had a headache. Their platelet count was 9,000-127,000. None were pregnant or postpartum.
“For us, as headache clinicians, the epidemiology of TTS overlaps with the epidemiology of migraine – they’re happening to the same group of patients,” Dr. Gelfand said. Most of the cases occurred in women aged 30-39 years, while the estimated incidence in women aged 50 or older is 0.9 cases per million doses.
The CDC has proceeded with the Johnson & Johnson vaccine because a risk-benefit analysis revealed that use of the vaccine will result in fewer hospitalization and deaths from COVID-19, compared with adverse events from the vaccine, Dr. Gelfand explained. However, the CDC notes that “women younger than 50 years old should be made aware of a rare risk of blood clots with low platelets following vaccination and the availability of other COVID-19 vaccines where this risk has not been observed.”
For clinicians, the existence of TTS raises a question when patients with a history of migraine call after having received the Johnson & Johnson vaccine, Dr. Gelfand said: “How do we know if this is a spontaneous attack, if it’s a headache provoked by receiving the vaccine, or they have one of these rare cases of [TTS]?”
Three things help with this differential, she said: timing, epidemiology, and headache phenotype. Headache after a vaccine is very common, but it usually happens within the first couple of hours or days after the vaccine. By day 4 after vaccination, few people had headaches in the clinical trials. Since TTS requires production of antibodies, a headache within a few hours of vaccination should not raise concerns about TTS. It should be considered, however, for patients who experience a headache within a week or 2 after vaccination.
Then consider the epidemiology: If it’s a woman between ages 18 and49 calling, the risk is higher than if it’s a male over age 50. Then consider whether there are any unusual headache features, positionality, encephalopathy, or clinical features that could suggest clots in other parts of the body, such as abdominal pain, shortness of breath, or pain in the legs.
“At the end of the day, if it’s a person who’s in this epidemiological window and they’re calling a week or 2 out from the Johnson & Johnson vaccine, we may just need to work it up and see,” Dr. Gelfand said. Work-up involves a CBC, a platelet count to see if they’re thrombocytopenic, and perhaps imaging, preferentially using MRI/MRV over CT since it’s a younger population. Treatment for CVST with thrombocytopenia is a nonheparin anticoagulant, and platelet transfusion should not occur before consulting with hematology.
Continue to vaccinate
“The big take home is that we should continue to vaccinate patients with migraine and that your current therapies do not interfere with the vaccine working and that the vaccine does not interact with our therapies,” Brian D. Loftus, MD, BSChE, immediate past president of the Southern Headache Society and a neurologist at Bellaire (Pa.) Neurology, said of the presentation. He also felt it was helpful to know that NSAIDs likely have no impact on the vaccines’ effectiveness as well.
“The most important new information for me was that the median onset of the CSVT was 8 days post vaccine,” Dr. Loftus said. “Typically, postvaccine headache is seen much sooner, within 1-2 days, so this is a useful clinical feature to separate out who needs to closer follow-up and possible neuroimaging.”
Given the epidemiology of those most likely to have TTS, Dr. Loftus said he would advise his female patients younger than 60 to simply get the Pfizer or Moderna vaccine since they appear safer for this demographic.
Dr. Gelfand is editor of the journal Headache but has no industry disclosures. Her spouse has received clinical trial grant support from Genentech and honoraria for editorial work from Dynamed Plus. Dr. Loftus has received grants or fees from Teva, Amgen, Abbvie, and Biohaven.
according to a presentation at the American Headache Society’s 2021 annual meeting.
Amy Gelfand, MD, director of pediatric headache at University of California, San Francisco, reviewed common concerns migraine patients or their clinicians might have related any of the three vaccines, starting with a review of how the vaccines work – by targeting the spike protein of the SARS-CoV-2 virus.
“The vaccines induce response to that protein, but only that protein, so there’s no reason to think they’re going to cause the body to produce neutralizing antibodies against any of our migraine therapeutics,” Dr. Gelfand said. She added that the phase 3 clinical trials included participants from a wide range of ages and comorbidities, so there were likely many people in the trials who have migraine, though no subgroup analyses have been performed for this group or are likely to be performed.
Common questions
The two treatments people have the most questions about concerning the COVID-19 vaccine are onabotulinumtoxinA and CGRP pathway monoclonal antibodies (mAbs), likely because both of these are injections, as is the vaccine, Dr. Gelfand said. First, she reminded attendees that onabotulinumtoxinA is not a dermal filler, since some reports following administration of the Moderna vaccine suggested that some people with dermal fillers had swelling in those areas after vaccination.
In addition, “there’s no reason to think the onabotulinumtoxinA would influence our body’s immune response to any vaccine, so there’s no need to retime the onabotulinumtoxinA injections around COVID-19 vaccine administration,” Dr. Gelfand said.
Regarding mAbs, she acknowledged that some white blood cells have CGRP receptors, which may have a pro- or anti-inflammatory role, but clinical trials of mAbs did not show any evidence of being immunosuppressive or myelosuppressive.
“The monoclonal antibodies themselves have undergone engineering so that they are just going after their one target,” Dr. Gelfand said. “They’re not going to be expected to bind to anything else outside of their targets, so I don’t think there’s anything there to make us retime the monoclonal antibody administration relative to the COVID-19 vaccine.”
She did note that patients who choose to get mAbs injections in their arm instead of their thigh or abdomen may want to receive it in the opposite arm than they one they have gotten or will get the vaccine in since the vaccine can cause discomfort.
The other common question patients may have is whether taking any NSAIDs or acetaminophen before getting the COVID-19 vaccine will reduce their immune response to the vaccination. This concern arises because of past evidence showing that some infants tended to have lower immunologic responses when they received acetaminophen after their primary vaccines’ series, but the clinical significance of those reduced responses is not clear since they still had strong responses. Further, this effect was not seen with booster shots, suggesting it’s an age-dependent effect.
During the clinical trials of the AstraZeneca vaccine, several sites gave prophylactic paracetamol without any apparent detrimental effect on antibody response, Dr. Gelfand said. Further, the mRNA and adenovirus-vectored vaccines appear to induce antibodies far above what many believe is needed for protection.
“Even if there were a slight decrease, it’s not clear that that would have any kind of clinical significance for that person in terms of their level of protection against COVID-19,” she said. “Bottom line, it’s fine for patients to use either of these after administration of the COVID-19 vaccine.” The Centers for Disease Control and Prevention doesn’t recommend it prophylactically beforehand, but it’s fine to take it for a fever, aches or headache after getting the vaccine.
Migraine or vaccine reaction?
Dr. Gelfand then addressed whether it should affect physicians’ headache differential if seeing a patient who recently received an adenovirus-vectored vaccine, such as the Johnson & Johnson or AstraZeneca vaccines. The question relates to the discovery of a very rare potential adverse event from these vaccines: cerebral venous sinus thrombosis (CVST) with thrombocytopenia and thromboses in other major vessels, together called thrombosis thrombocytopenia syndrome (TTS). No TTS cases have been reported following mRNA vaccines.
TTS’s mechanism appears similar to autoimmune heparin-induced thrombocytopenia, where the body produces platelet-activating antibodies. TTS currently has three diagnostic criteria: new-onset thrombocytopenia (<150,000/microliter) without evidence of platelet clumping, venous or arterial thrombosis, and absence of prior exposure to heparin.
So far, TTS has been limited only to the vaccines that use an adenovirus vector. One male clinical trial participant experienced CVST with thrombocytopenia in Johnson & Johnson phase 3 trials, and 12 cases out of approximately 8 million Johnson & Johnson doses were reported to the Vaccine Adverse Event Reporting System between March 2 and April 21, 2021. Three TTS more cases followed these, resulting in 15 TTS events per 8 million doses.
In terms of clinical features, all 15 cases were females under age 60, mostly white, and all 11 who were tested were positive for the heparin-platelet factor 4 antibody test. TTS occurred 6-15 days after vaccination for these cases, and all but one had a headache. Their platelet count was 9,000-127,000. None were pregnant or postpartum.
“For us, as headache clinicians, the epidemiology of TTS overlaps with the epidemiology of migraine – they’re happening to the same group of patients,” Dr. Gelfand said. Most of the cases occurred in women aged 30-39 years, while the estimated incidence in women aged 50 or older is 0.9 cases per million doses.
The CDC has proceeded with the Johnson & Johnson vaccine because a risk-benefit analysis revealed that use of the vaccine will result in fewer hospitalization and deaths from COVID-19, compared with adverse events from the vaccine, Dr. Gelfand explained. However, the CDC notes that “women younger than 50 years old should be made aware of a rare risk of blood clots with low platelets following vaccination and the availability of other COVID-19 vaccines where this risk has not been observed.”
For clinicians, the existence of TTS raises a question when patients with a history of migraine call after having received the Johnson & Johnson vaccine, Dr. Gelfand said: “How do we know if this is a spontaneous attack, if it’s a headache provoked by receiving the vaccine, or they have one of these rare cases of [TTS]?”
Three things help with this differential, she said: timing, epidemiology, and headache phenotype. Headache after a vaccine is very common, but it usually happens within the first couple of hours or days after the vaccine. By day 4 after vaccination, few people had headaches in the clinical trials. Since TTS requires production of antibodies, a headache within a few hours of vaccination should not raise concerns about TTS. It should be considered, however, for patients who experience a headache within a week or 2 after vaccination.
Then consider the epidemiology: If it’s a woman between ages 18 and49 calling, the risk is higher than if it’s a male over age 50. Then consider whether there are any unusual headache features, positionality, encephalopathy, or clinical features that could suggest clots in other parts of the body, such as abdominal pain, shortness of breath, or pain in the legs.
“At the end of the day, if it’s a person who’s in this epidemiological window and they’re calling a week or 2 out from the Johnson & Johnson vaccine, we may just need to work it up and see,” Dr. Gelfand said. Work-up involves a CBC, a platelet count to see if they’re thrombocytopenic, and perhaps imaging, preferentially using MRI/MRV over CT since it’s a younger population. Treatment for CVST with thrombocytopenia is a nonheparin anticoagulant, and platelet transfusion should not occur before consulting with hematology.
Continue to vaccinate
“The big take home is that we should continue to vaccinate patients with migraine and that your current therapies do not interfere with the vaccine working and that the vaccine does not interact with our therapies,” Brian D. Loftus, MD, BSChE, immediate past president of the Southern Headache Society and a neurologist at Bellaire (Pa.) Neurology, said of the presentation. He also felt it was helpful to know that NSAIDs likely have no impact on the vaccines’ effectiveness as well.
“The most important new information for me was that the median onset of the CSVT was 8 days post vaccine,” Dr. Loftus said. “Typically, postvaccine headache is seen much sooner, within 1-2 days, so this is a useful clinical feature to separate out who needs to closer follow-up and possible neuroimaging.”
Given the epidemiology of those most likely to have TTS, Dr. Loftus said he would advise his female patients younger than 60 to simply get the Pfizer or Moderna vaccine since they appear safer for this demographic.
Dr. Gelfand is editor of the journal Headache but has no industry disclosures. Her spouse has received clinical trial grant support from Genentech and honoraria for editorial work from Dynamed Plus. Dr. Loftus has received grants or fees from Teva, Amgen, Abbvie, and Biohaven.
according to a presentation at the American Headache Society’s 2021 annual meeting.
Amy Gelfand, MD, director of pediatric headache at University of California, San Francisco, reviewed common concerns migraine patients or their clinicians might have related any of the three vaccines, starting with a review of how the vaccines work – by targeting the spike protein of the SARS-CoV-2 virus.
“The vaccines induce response to that protein, but only that protein, so there’s no reason to think they’re going to cause the body to produce neutralizing antibodies against any of our migraine therapeutics,” Dr. Gelfand said. She added that the phase 3 clinical trials included participants from a wide range of ages and comorbidities, so there were likely many people in the trials who have migraine, though no subgroup analyses have been performed for this group or are likely to be performed.
Common questions
The two treatments people have the most questions about concerning the COVID-19 vaccine are onabotulinumtoxinA and CGRP pathway monoclonal antibodies (mAbs), likely because both of these are injections, as is the vaccine, Dr. Gelfand said. First, she reminded attendees that onabotulinumtoxinA is not a dermal filler, since some reports following administration of the Moderna vaccine suggested that some people with dermal fillers had swelling in those areas after vaccination.
In addition, “there’s no reason to think the onabotulinumtoxinA would influence our body’s immune response to any vaccine, so there’s no need to retime the onabotulinumtoxinA injections around COVID-19 vaccine administration,” Dr. Gelfand said.
Regarding mAbs, she acknowledged that some white blood cells have CGRP receptors, which may have a pro- or anti-inflammatory role, but clinical trials of mAbs did not show any evidence of being immunosuppressive or myelosuppressive.
“The monoclonal antibodies themselves have undergone engineering so that they are just going after their one target,” Dr. Gelfand said. “They’re not going to be expected to bind to anything else outside of their targets, so I don’t think there’s anything there to make us retime the monoclonal antibody administration relative to the COVID-19 vaccine.”
She did note that patients who choose to get mAbs injections in their arm instead of their thigh or abdomen may want to receive it in the opposite arm than they one they have gotten or will get the vaccine in since the vaccine can cause discomfort.
The other common question patients may have is whether taking any NSAIDs or acetaminophen before getting the COVID-19 vaccine will reduce their immune response to the vaccination. This concern arises because of past evidence showing that some infants tended to have lower immunologic responses when they received acetaminophen after their primary vaccines’ series, but the clinical significance of those reduced responses is not clear since they still had strong responses. Further, this effect was not seen with booster shots, suggesting it’s an age-dependent effect.
During the clinical trials of the AstraZeneca vaccine, several sites gave prophylactic paracetamol without any apparent detrimental effect on antibody response, Dr. Gelfand said. Further, the mRNA and adenovirus-vectored vaccines appear to induce antibodies far above what many believe is needed for protection.
“Even if there were a slight decrease, it’s not clear that that would have any kind of clinical significance for that person in terms of their level of protection against COVID-19,” she said. “Bottom line, it’s fine for patients to use either of these after administration of the COVID-19 vaccine.” The Centers for Disease Control and Prevention doesn’t recommend it prophylactically beforehand, but it’s fine to take it for a fever, aches or headache after getting the vaccine.
Migraine or vaccine reaction?
Dr. Gelfand then addressed whether it should affect physicians’ headache differential if seeing a patient who recently received an adenovirus-vectored vaccine, such as the Johnson & Johnson or AstraZeneca vaccines. The question relates to the discovery of a very rare potential adverse event from these vaccines: cerebral venous sinus thrombosis (CVST) with thrombocytopenia and thromboses in other major vessels, together called thrombosis thrombocytopenia syndrome (TTS). No TTS cases have been reported following mRNA vaccines.
TTS’s mechanism appears similar to autoimmune heparin-induced thrombocytopenia, where the body produces platelet-activating antibodies. TTS currently has three diagnostic criteria: new-onset thrombocytopenia (<150,000/microliter) without evidence of platelet clumping, venous or arterial thrombosis, and absence of prior exposure to heparin.
So far, TTS has been limited only to the vaccines that use an adenovirus vector. One male clinical trial participant experienced CVST with thrombocytopenia in Johnson & Johnson phase 3 trials, and 12 cases out of approximately 8 million Johnson & Johnson doses were reported to the Vaccine Adverse Event Reporting System between March 2 and April 21, 2021. Three TTS more cases followed these, resulting in 15 TTS events per 8 million doses.
In terms of clinical features, all 15 cases were females under age 60, mostly white, and all 11 who were tested were positive for the heparin-platelet factor 4 antibody test. TTS occurred 6-15 days after vaccination for these cases, and all but one had a headache. Their platelet count was 9,000-127,000. None were pregnant or postpartum.
“For us, as headache clinicians, the epidemiology of TTS overlaps with the epidemiology of migraine – they’re happening to the same group of patients,” Dr. Gelfand said. Most of the cases occurred in women aged 30-39 years, while the estimated incidence in women aged 50 or older is 0.9 cases per million doses.
The CDC has proceeded with the Johnson & Johnson vaccine because a risk-benefit analysis revealed that use of the vaccine will result in fewer hospitalization and deaths from COVID-19, compared with adverse events from the vaccine, Dr. Gelfand explained. However, the CDC notes that “women younger than 50 years old should be made aware of a rare risk of blood clots with low platelets following vaccination and the availability of other COVID-19 vaccines where this risk has not been observed.”
For clinicians, the existence of TTS raises a question when patients with a history of migraine call after having received the Johnson & Johnson vaccine, Dr. Gelfand said: “How do we know if this is a spontaneous attack, if it’s a headache provoked by receiving the vaccine, or they have one of these rare cases of [TTS]?”
Three things help with this differential, she said: timing, epidemiology, and headache phenotype. Headache after a vaccine is very common, but it usually happens within the first couple of hours or days after the vaccine. By day 4 after vaccination, few people had headaches in the clinical trials. Since TTS requires production of antibodies, a headache within a few hours of vaccination should not raise concerns about TTS. It should be considered, however, for patients who experience a headache within a week or 2 after vaccination.
Then consider the epidemiology: If it’s a woman between ages 18 and49 calling, the risk is higher than if it’s a male over age 50. Then consider whether there are any unusual headache features, positionality, encephalopathy, or clinical features that could suggest clots in other parts of the body, such as abdominal pain, shortness of breath, or pain in the legs.
“At the end of the day, if it’s a person who’s in this epidemiological window and they’re calling a week or 2 out from the Johnson & Johnson vaccine, we may just need to work it up and see,” Dr. Gelfand said. Work-up involves a CBC, a platelet count to see if they’re thrombocytopenic, and perhaps imaging, preferentially using MRI/MRV over CT since it’s a younger population. Treatment for CVST with thrombocytopenia is a nonheparin anticoagulant, and platelet transfusion should not occur before consulting with hematology.
Continue to vaccinate
“The big take home is that we should continue to vaccinate patients with migraine and that your current therapies do not interfere with the vaccine working and that the vaccine does not interact with our therapies,” Brian D. Loftus, MD, BSChE, immediate past president of the Southern Headache Society and a neurologist at Bellaire (Pa.) Neurology, said of the presentation. He also felt it was helpful to know that NSAIDs likely have no impact on the vaccines’ effectiveness as well.
“The most important new information for me was that the median onset of the CSVT was 8 days post vaccine,” Dr. Loftus said. “Typically, postvaccine headache is seen much sooner, within 1-2 days, so this is a useful clinical feature to separate out who needs to closer follow-up and possible neuroimaging.”
Given the epidemiology of those most likely to have TTS, Dr. Loftus said he would advise his female patients younger than 60 to simply get the Pfizer or Moderna vaccine since they appear safer for this demographic.
Dr. Gelfand is editor of the journal Headache but has no industry disclosures. Her spouse has received clinical trial grant support from Genentech and honoraria for editorial work from Dynamed Plus. Dr. Loftus has received grants or fees from Teva, Amgen, Abbvie, and Biohaven.
FROM AHS 2021
BBB integrity linked to cortical spreading depression
CSD has been linked to migraine aura, but a connection to pain symptoms is uncertain. “There’s just a lack of knowledge. We don’t understand migraine pathophysiology,” said Michael G. Harrington, MBChB, who was asked to comment on the study.
“The evidence for altered transport across the barrier in cortical spreading depression and the associated aura of migraine is pretty strong. The evidence for regular migraine, not so. In fact, there’s really no strong evidence for leakage in those people, and so it is still unresolved whether this initial cortical spreading depression that occurs in aura then triggers migraine afterwards, because it’s occurring during the aura. And in people who do not have the aura, is there a silent cortical spreading depression phenomenon with some leakage that triggers the migraine? That question is definitely not answered,” said Dr. Harrington, a research professor of neurology at the University of Southern California, Los Angeles.
Leakage of the BBB might allow passage of nociceptive compounds that could trigger migraine. Loss of BBB integrity has also been seen in other central nervous system pain disorders, suggesting that alterations to BBB functioning could have broader implications.
“In this model that we’re using, we’re seeing loss of overall barrier integrity, which lends itself to a whole cascade of further pathological possibilities,” Jared Wahl, a PhD candidate at the University of Arizona, Tucson, said in an interview. He presented the research at the American Headache Society’s 2021 annual meeting.
A leaky BBB could allow infiltration of a range of substances, but the potential for such a mechanism in migraine pathology is not well understood.
The researchers specifically investigated the potential role of claudin-5 in the tight junction (TJ) region of the BBB. The decision was made in part because the proteins involved in the BBB are difficult to study, and there is some familiarity with claudin-5, according to Mr. Wahl. ”Of all the proteins that are out there, for claudin-5 (there are) somewhat better techniques and products available to work with, and there’s been some previous research done to show that it’s implicated in blood brain barrier pathology. So it seemed like a good candidate to start with investigating this whole possible pathophysiological link between barrier disruption and migration of pronociceptive substances into the CNS during migraine attacks,” he said. The claudin proteins are also the major components of the tight junctions that seal off gaps between endothelial cells along the BBB.
Dynamic changes seen in the in vitro model
To simulate a CSD event, the researchers pulsed cultured cells for 5 minutes with astrocyte-conditioned media, artificial cerebrospinal fluid, KCl, glutamate, altered pH, or adenosine triphosphate (ATP). They used trans endothelial electrical resistance (TEER) to quickly and qualitatively screen for loss of barrier integrity, which is characterized by loss of electrical resistance. To quantify the magnitude of a breach, the researchers applied carbon-14 (C14)–labeled sucrose to one side of the barrier, and determined the amount of labeled sucrose transmitted to the other side of the barrier.
ATP and pH pulses that were outside normal physiological limits led to permeability. The team then used immunocytochemistry assays to visualize the condition of the model BBB, and found discontinuity of the tight junction membranes. Imaging of claudin-5 showed organizational changes within the tight junction, but there was no change in expression level, suggesting that the alterations were due to dynamic reorganization, according to Mr. Wahl.
Transient openings could allow passage of molecules such as bradykinin, calcitonin gene-related peptide (CGRP), and substance P, which could go on to affect the trigeminal nerve complex and trigger a migraine. “That’s sort of the crux of a lot of this migraine research, is gluing this physiological (mechanism) to how it is actually activating the CNS. And this is sort of where we’re going with it at the moment,” said Mr. Wahl.
Next steps
The researchers next plan to generate a cell line with claudin-5 linked to green fluorescent protein, then use confocal microscopy to image claudin-5 in real time as the BBB model responds to a simulated CSD.
Another important step will be to link physiological findings like those presented by Mr. Wahl to migraine-specific mechanisms. The results from this model will need to be expanded to include more than endothelial cells, especially astrocytes, pericytes, and neurons, as well as organoids, brain slices, or in vivo animal models, according to Dr. Harrington. “I think you could try and block the changes in occludin [another protein in the tight junction] or claudin-5 to see if, under the same provocation, that prevented the changes in a migraine model. That would be a direct way of connecting from CSD to migraine,” said Dr. Harrington.
If BBB disruption is confirmed to play an important role in migraine, and claudin-5 or other specific proteins are confirmed to be the cause, it could have clinical implications. A drug that could prevent those changes in the proteins and prevent a leak in the BBB could be a migraine preventative. “That could help prevent things like nociceptive substances migrating into the CNS, and could possibly be a well-tolerated drug target that doesn’t have the side effects or the overuse problems that a lot of stuff on the market has today,” said Mr. Wahl.
CSD has been linked to migraine aura, but a connection to pain symptoms is uncertain. “There’s just a lack of knowledge. We don’t understand migraine pathophysiology,” said Michael G. Harrington, MBChB, who was asked to comment on the study.
“The evidence for altered transport across the barrier in cortical spreading depression and the associated aura of migraine is pretty strong. The evidence for regular migraine, not so. In fact, there’s really no strong evidence for leakage in those people, and so it is still unresolved whether this initial cortical spreading depression that occurs in aura then triggers migraine afterwards, because it’s occurring during the aura. And in people who do not have the aura, is there a silent cortical spreading depression phenomenon with some leakage that triggers the migraine? That question is definitely not answered,” said Dr. Harrington, a research professor of neurology at the University of Southern California, Los Angeles.
Leakage of the BBB might allow passage of nociceptive compounds that could trigger migraine. Loss of BBB integrity has also been seen in other central nervous system pain disorders, suggesting that alterations to BBB functioning could have broader implications.
“In this model that we’re using, we’re seeing loss of overall barrier integrity, which lends itself to a whole cascade of further pathological possibilities,” Jared Wahl, a PhD candidate at the University of Arizona, Tucson, said in an interview. He presented the research at the American Headache Society’s 2021 annual meeting.
A leaky BBB could allow infiltration of a range of substances, but the potential for such a mechanism in migraine pathology is not well understood.
The researchers specifically investigated the potential role of claudin-5 in the tight junction (TJ) region of the BBB. The decision was made in part because the proteins involved in the BBB are difficult to study, and there is some familiarity with claudin-5, according to Mr. Wahl. ”Of all the proteins that are out there, for claudin-5 (there are) somewhat better techniques and products available to work with, and there’s been some previous research done to show that it’s implicated in blood brain barrier pathology. So it seemed like a good candidate to start with investigating this whole possible pathophysiological link between barrier disruption and migration of pronociceptive substances into the CNS during migraine attacks,” he said. The claudin proteins are also the major components of the tight junctions that seal off gaps between endothelial cells along the BBB.
Dynamic changes seen in the in vitro model
To simulate a CSD event, the researchers pulsed cultured cells for 5 minutes with astrocyte-conditioned media, artificial cerebrospinal fluid, KCl, glutamate, altered pH, or adenosine triphosphate (ATP). They used trans endothelial electrical resistance (TEER) to quickly and qualitatively screen for loss of barrier integrity, which is characterized by loss of electrical resistance. To quantify the magnitude of a breach, the researchers applied carbon-14 (C14)–labeled sucrose to one side of the barrier, and determined the amount of labeled sucrose transmitted to the other side of the barrier.
ATP and pH pulses that were outside normal physiological limits led to permeability. The team then used immunocytochemistry assays to visualize the condition of the model BBB, and found discontinuity of the tight junction membranes. Imaging of claudin-5 showed organizational changes within the tight junction, but there was no change in expression level, suggesting that the alterations were due to dynamic reorganization, according to Mr. Wahl.
Transient openings could allow passage of molecules such as bradykinin, calcitonin gene-related peptide (CGRP), and substance P, which could go on to affect the trigeminal nerve complex and trigger a migraine. “That’s sort of the crux of a lot of this migraine research, is gluing this physiological (mechanism) to how it is actually activating the CNS. And this is sort of where we’re going with it at the moment,” said Mr. Wahl.
Next steps
The researchers next plan to generate a cell line with claudin-5 linked to green fluorescent protein, then use confocal microscopy to image claudin-5 in real time as the BBB model responds to a simulated CSD.
Another important step will be to link physiological findings like those presented by Mr. Wahl to migraine-specific mechanisms. The results from this model will need to be expanded to include more than endothelial cells, especially astrocytes, pericytes, and neurons, as well as organoids, brain slices, or in vivo animal models, according to Dr. Harrington. “I think you could try and block the changes in occludin [another protein in the tight junction] or claudin-5 to see if, under the same provocation, that prevented the changes in a migraine model. That would be a direct way of connecting from CSD to migraine,” said Dr. Harrington.
If BBB disruption is confirmed to play an important role in migraine, and claudin-5 or other specific proteins are confirmed to be the cause, it could have clinical implications. A drug that could prevent those changes in the proteins and prevent a leak in the BBB could be a migraine preventative. “That could help prevent things like nociceptive substances migrating into the CNS, and could possibly be a well-tolerated drug target that doesn’t have the side effects or the overuse problems that a lot of stuff on the market has today,” said Mr. Wahl.
CSD has been linked to migraine aura, but a connection to pain symptoms is uncertain. “There’s just a lack of knowledge. We don’t understand migraine pathophysiology,” said Michael G. Harrington, MBChB, who was asked to comment on the study.
“The evidence for altered transport across the barrier in cortical spreading depression and the associated aura of migraine is pretty strong. The evidence for regular migraine, not so. In fact, there’s really no strong evidence for leakage in those people, and so it is still unresolved whether this initial cortical spreading depression that occurs in aura then triggers migraine afterwards, because it’s occurring during the aura. And in people who do not have the aura, is there a silent cortical spreading depression phenomenon with some leakage that triggers the migraine? That question is definitely not answered,” said Dr. Harrington, a research professor of neurology at the University of Southern California, Los Angeles.
Leakage of the BBB might allow passage of nociceptive compounds that could trigger migraine. Loss of BBB integrity has also been seen in other central nervous system pain disorders, suggesting that alterations to BBB functioning could have broader implications.
“In this model that we’re using, we’re seeing loss of overall barrier integrity, which lends itself to a whole cascade of further pathological possibilities,” Jared Wahl, a PhD candidate at the University of Arizona, Tucson, said in an interview. He presented the research at the American Headache Society’s 2021 annual meeting.
A leaky BBB could allow infiltration of a range of substances, but the potential for such a mechanism in migraine pathology is not well understood.
The researchers specifically investigated the potential role of claudin-5 in the tight junction (TJ) region of the BBB. The decision was made in part because the proteins involved in the BBB are difficult to study, and there is some familiarity with claudin-5, according to Mr. Wahl. ”Of all the proteins that are out there, for claudin-5 (there are) somewhat better techniques and products available to work with, and there’s been some previous research done to show that it’s implicated in blood brain barrier pathology. So it seemed like a good candidate to start with investigating this whole possible pathophysiological link between barrier disruption and migration of pronociceptive substances into the CNS during migraine attacks,” he said. The claudin proteins are also the major components of the tight junctions that seal off gaps between endothelial cells along the BBB.
Dynamic changes seen in the in vitro model
To simulate a CSD event, the researchers pulsed cultured cells for 5 minutes with astrocyte-conditioned media, artificial cerebrospinal fluid, KCl, glutamate, altered pH, or adenosine triphosphate (ATP). They used trans endothelial electrical resistance (TEER) to quickly and qualitatively screen for loss of barrier integrity, which is characterized by loss of electrical resistance. To quantify the magnitude of a breach, the researchers applied carbon-14 (C14)–labeled sucrose to one side of the barrier, and determined the amount of labeled sucrose transmitted to the other side of the barrier.
ATP and pH pulses that were outside normal physiological limits led to permeability. The team then used immunocytochemistry assays to visualize the condition of the model BBB, and found discontinuity of the tight junction membranes. Imaging of claudin-5 showed organizational changes within the tight junction, but there was no change in expression level, suggesting that the alterations were due to dynamic reorganization, according to Mr. Wahl.
Transient openings could allow passage of molecules such as bradykinin, calcitonin gene-related peptide (CGRP), and substance P, which could go on to affect the trigeminal nerve complex and trigger a migraine. “That’s sort of the crux of a lot of this migraine research, is gluing this physiological (mechanism) to how it is actually activating the CNS. And this is sort of where we’re going with it at the moment,” said Mr. Wahl.
Next steps
The researchers next plan to generate a cell line with claudin-5 linked to green fluorescent protein, then use confocal microscopy to image claudin-5 in real time as the BBB model responds to a simulated CSD.
Another important step will be to link physiological findings like those presented by Mr. Wahl to migraine-specific mechanisms. The results from this model will need to be expanded to include more than endothelial cells, especially astrocytes, pericytes, and neurons, as well as organoids, brain slices, or in vivo animal models, according to Dr. Harrington. “I think you could try and block the changes in occludin [another protein in the tight junction] or claudin-5 to see if, under the same provocation, that prevented the changes in a migraine model. That would be a direct way of connecting from CSD to migraine,” said Dr. Harrington.
If BBB disruption is confirmed to play an important role in migraine, and claudin-5 or other specific proteins are confirmed to be the cause, it could have clinical implications. A drug that could prevent those changes in the proteins and prevent a leak in the BBB could be a migraine preventative. “That could help prevent things like nociceptive substances migrating into the CNS, and could possibly be a well-tolerated drug target that doesn’t have the side effects or the overuse problems that a lot of stuff on the market has today,” said Mr. Wahl.
FROM AHS 2021
No increased risk of hypertension with erenumab?
, easing earlier concerns that this may be one of the drug’s adverse events, an analysis of postmarketing data shows. Nevertheless, investigators noted that more research is needed to confirm that this is the case.
While randomized clinical trials have shown no increased risk of hypertension related to the drug, it has been reported in postmarketing data. However, many of these events occurred in patients with previously documented hypertension or risk factors for the disorder, the investigators noted.
The rate of hypertension adverse events in postmarketing data was 0.144 per 100 person-years. Most such reports described only one instance of elevated blood pressure. In April 2020, the prescribing information for the drug was updated to include a mention of the risk of hypertension.
“Given the limitations of postmarketing reports, including incomplete information, lack of a control arm, and others, additional data are certainly needed to fully characterize the nature, the timing, and the extent to which hypertension is a risk associated with erenumab, and indeed other [calcitonin-gene-related peptide (CGRP)] pathway antagonists,” said study investigator David W. Dodick, MD, professor of neurology at the Mayo Clinic College of Medicine, Phoenix.
The findings were presented at the American Headache Society’s 2021 annual meeting.
No increased risk over time
A monoclonal antibody and CGRP antagonist, erenumab is approved in the United States for migraine prevention in adults. CGRP medications are vasodilators, and, therefore, migraine treatments that target this pathway could theoretically have hypertensive effects.
To assess the risk of hypertension in migraine patients treated with erenumab, investigators examined clinical trial and postmarketing data. The analysis included cases with limited information and patients with a different etiology for the development of hypertension.
Using Amgen Clinical Trial data, the researchers performed a pooled safety analysis of four placebo-controlled, double-blind phase 2 or 3 studies of the drug. Participants had episodic or chronic migraine and were between ages 18 and 60 years or age 65 years. The doses studied were 70 mg and 140 mg.
In these studies, blood pressure data for each patient were based on an average of at least two measurements taken after patients were in rested state for at least 5 minutes. The position used for blood pressure measurement for each patient was consistent throughout the study.
The investigators also analyzed postmarketing reports of hypertension from May 17, 2018, to Jan. 31, 2020, identified in Amgen Global Safety data.
The pooled studies included 1,043 participants receiving placebo, 893 receiving 70 mg of erenumab, and 507 receiving 140 mg of the drug. During the treatment phase, the incidence of hypertension was 0.9% among controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group. The proportion of patients who started a new antihypertensive medication was 1.2% in controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group.
In a long-term, open-label study, patients with episodic migraine received erenumab treatment for up to 5 years. The incidence of hypertension did not increase with time in this population.
The postmarketing data encompassed 245,682 person-years of erenumab exposure. The researchers identified 362 hypertension events (355 cases). The rate of these events was 0.144 per 100 person-years. The exposure-adjusted incidence of hypertension was 1.9 per 100 patient-years for erenumab.
Of the 362 hypertensive events, 158 (43.6%) were in patients with a medical history of hypertension or risk factors for hypertension. Information about the time to onset of hypertension was available for 121 (33.4%) adverse events.
Of this group, 56 (46.2%) occurred within 1 week of erenumab initiation, including 43 (35.5%) that occurred within 1 day. This rapid time to hypertension onset “is inconsistent with the pharmacokinetic profile of once-monthly erenumab 70 mg or 140 mg, which has a peak serum concentration in approximately 6 days,” said Dr. Dodick.
Hypertension ‘not a barrier’ to treatment
Commenting on the findings, Richard B. Lipton, MD, Edwin S. Lowe professor and vice chair of neurology at Albert Einstein College of Medicine, New York, noted that in theory blocking CGRP could increase blood pressure. However, he noted that the data and clinical experience do not suggest erenumab poses a serious risk.
“I have rarely seen new-onset hypertension with erenumab in the patients treated at our medical center. The few cases I have seen were in older adults with pre-existing hypertension,” he said.
The investigators’ review of clinical trial data together with global safety databases was a strength of their study, said Dr. Lipton. In clinical trials, patients are monitored carefully, and a placebo control group aids in the determination of background rates.
“In the trials, the incidence of new-onset hypertension or hypertension exacerbation was 0.9%, while the placebo rate was 0.2%,” said Dr. Lipton. “The absolute increase in the risk of hypertension was 0.6% or six cases per thousand: A low rate.” But clinical trials enroll carefully selected patients who do not represent the broad group of people treated with erenumab in clinical practice, he added.
The global safety data are more representative of patients who receive erenumab in real-world settings. The weaknesses of these data, though, are the lack of a control group and the incomplete ascertainment of data associated with spontaneous reporting.
Yet both types of studies, with their complementary strengths and weaknesses, indicated low rates of hypertension.
“The low incidence of hypertension, in my view, is not a barrier to the use of erenumab, though checking blood pressure after starting any new migraine therapy is prudent,” Dr. Lipton concluded.
The study was funded by Amgen. Dr. Dodick had no relevant disclosures. Dr. Lipton has consulted for and conducted studies funded by Amgen and by other companies that manufacture CGRP drugs. He has stock options in Biohaven.
A version of this article first appeared on Medscape.com.
, easing earlier concerns that this may be one of the drug’s adverse events, an analysis of postmarketing data shows. Nevertheless, investigators noted that more research is needed to confirm that this is the case.
While randomized clinical trials have shown no increased risk of hypertension related to the drug, it has been reported in postmarketing data. However, many of these events occurred in patients with previously documented hypertension or risk factors for the disorder, the investigators noted.
The rate of hypertension adverse events in postmarketing data was 0.144 per 100 person-years. Most such reports described only one instance of elevated blood pressure. In April 2020, the prescribing information for the drug was updated to include a mention of the risk of hypertension.
“Given the limitations of postmarketing reports, including incomplete information, lack of a control arm, and others, additional data are certainly needed to fully characterize the nature, the timing, and the extent to which hypertension is a risk associated with erenumab, and indeed other [calcitonin-gene-related peptide (CGRP)] pathway antagonists,” said study investigator David W. Dodick, MD, professor of neurology at the Mayo Clinic College of Medicine, Phoenix.
The findings were presented at the American Headache Society’s 2021 annual meeting.
No increased risk over time
A monoclonal antibody and CGRP antagonist, erenumab is approved in the United States for migraine prevention in adults. CGRP medications are vasodilators, and, therefore, migraine treatments that target this pathway could theoretically have hypertensive effects.
To assess the risk of hypertension in migraine patients treated with erenumab, investigators examined clinical trial and postmarketing data. The analysis included cases with limited information and patients with a different etiology for the development of hypertension.
Using Amgen Clinical Trial data, the researchers performed a pooled safety analysis of four placebo-controlled, double-blind phase 2 or 3 studies of the drug. Participants had episodic or chronic migraine and were between ages 18 and 60 years or age 65 years. The doses studied were 70 mg and 140 mg.
In these studies, blood pressure data for each patient were based on an average of at least two measurements taken after patients were in rested state for at least 5 minutes. The position used for blood pressure measurement for each patient was consistent throughout the study.
The investigators also analyzed postmarketing reports of hypertension from May 17, 2018, to Jan. 31, 2020, identified in Amgen Global Safety data.
The pooled studies included 1,043 participants receiving placebo, 893 receiving 70 mg of erenumab, and 507 receiving 140 mg of the drug. During the treatment phase, the incidence of hypertension was 0.9% among controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group. The proportion of patients who started a new antihypertensive medication was 1.2% in controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group.
In a long-term, open-label study, patients with episodic migraine received erenumab treatment for up to 5 years. The incidence of hypertension did not increase with time in this population.
The postmarketing data encompassed 245,682 person-years of erenumab exposure. The researchers identified 362 hypertension events (355 cases). The rate of these events was 0.144 per 100 person-years. The exposure-adjusted incidence of hypertension was 1.9 per 100 patient-years for erenumab.
Of the 362 hypertensive events, 158 (43.6%) were in patients with a medical history of hypertension or risk factors for hypertension. Information about the time to onset of hypertension was available for 121 (33.4%) adverse events.
Of this group, 56 (46.2%) occurred within 1 week of erenumab initiation, including 43 (35.5%) that occurred within 1 day. This rapid time to hypertension onset “is inconsistent with the pharmacokinetic profile of once-monthly erenumab 70 mg or 140 mg, which has a peak serum concentration in approximately 6 days,” said Dr. Dodick.
Hypertension ‘not a barrier’ to treatment
Commenting on the findings, Richard B. Lipton, MD, Edwin S. Lowe professor and vice chair of neurology at Albert Einstein College of Medicine, New York, noted that in theory blocking CGRP could increase blood pressure. However, he noted that the data and clinical experience do not suggest erenumab poses a serious risk.
“I have rarely seen new-onset hypertension with erenumab in the patients treated at our medical center. The few cases I have seen were in older adults with pre-existing hypertension,” he said.
The investigators’ review of clinical trial data together with global safety databases was a strength of their study, said Dr. Lipton. In clinical trials, patients are monitored carefully, and a placebo control group aids in the determination of background rates.
“In the trials, the incidence of new-onset hypertension or hypertension exacerbation was 0.9%, while the placebo rate was 0.2%,” said Dr. Lipton. “The absolute increase in the risk of hypertension was 0.6% or six cases per thousand: A low rate.” But clinical trials enroll carefully selected patients who do not represent the broad group of people treated with erenumab in clinical practice, he added.
The global safety data are more representative of patients who receive erenumab in real-world settings. The weaknesses of these data, though, are the lack of a control group and the incomplete ascertainment of data associated with spontaneous reporting.
Yet both types of studies, with their complementary strengths and weaknesses, indicated low rates of hypertension.
“The low incidence of hypertension, in my view, is not a barrier to the use of erenumab, though checking blood pressure after starting any new migraine therapy is prudent,” Dr. Lipton concluded.
The study was funded by Amgen. Dr. Dodick had no relevant disclosures. Dr. Lipton has consulted for and conducted studies funded by Amgen and by other companies that manufacture CGRP drugs. He has stock options in Biohaven.
A version of this article first appeared on Medscape.com.
, easing earlier concerns that this may be one of the drug’s adverse events, an analysis of postmarketing data shows. Nevertheless, investigators noted that more research is needed to confirm that this is the case.
While randomized clinical trials have shown no increased risk of hypertension related to the drug, it has been reported in postmarketing data. However, many of these events occurred in patients with previously documented hypertension or risk factors for the disorder, the investigators noted.
The rate of hypertension adverse events in postmarketing data was 0.144 per 100 person-years. Most such reports described only one instance of elevated blood pressure. In April 2020, the prescribing information for the drug was updated to include a mention of the risk of hypertension.
“Given the limitations of postmarketing reports, including incomplete information, lack of a control arm, and others, additional data are certainly needed to fully characterize the nature, the timing, and the extent to which hypertension is a risk associated with erenumab, and indeed other [calcitonin-gene-related peptide (CGRP)] pathway antagonists,” said study investigator David W. Dodick, MD, professor of neurology at the Mayo Clinic College of Medicine, Phoenix.
The findings were presented at the American Headache Society’s 2021 annual meeting.
No increased risk over time
A monoclonal antibody and CGRP antagonist, erenumab is approved in the United States for migraine prevention in adults. CGRP medications are vasodilators, and, therefore, migraine treatments that target this pathway could theoretically have hypertensive effects.
To assess the risk of hypertension in migraine patients treated with erenumab, investigators examined clinical trial and postmarketing data. The analysis included cases with limited information and patients with a different etiology for the development of hypertension.
Using Amgen Clinical Trial data, the researchers performed a pooled safety analysis of four placebo-controlled, double-blind phase 2 or 3 studies of the drug. Participants had episodic or chronic migraine and were between ages 18 and 60 years or age 65 years. The doses studied were 70 mg and 140 mg.
In these studies, blood pressure data for each patient were based on an average of at least two measurements taken after patients were in rested state for at least 5 minutes. The position used for blood pressure measurement for each patient was consistent throughout the study.
The investigators also analyzed postmarketing reports of hypertension from May 17, 2018, to Jan. 31, 2020, identified in Amgen Global Safety data.
The pooled studies included 1,043 participants receiving placebo, 893 receiving 70 mg of erenumab, and 507 receiving 140 mg of the drug. During the treatment phase, the incidence of hypertension was 0.9% among controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group. The proportion of patients who started a new antihypertensive medication was 1.2% in controls, 0.8% in the 70-mg group, and 0.2% in the 140-mg group.
In a long-term, open-label study, patients with episodic migraine received erenumab treatment for up to 5 years. The incidence of hypertension did not increase with time in this population.
The postmarketing data encompassed 245,682 person-years of erenumab exposure. The researchers identified 362 hypertension events (355 cases). The rate of these events was 0.144 per 100 person-years. The exposure-adjusted incidence of hypertension was 1.9 per 100 patient-years for erenumab.
Of the 362 hypertensive events, 158 (43.6%) were in patients with a medical history of hypertension or risk factors for hypertension. Information about the time to onset of hypertension was available for 121 (33.4%) adverse events.
Of this group, 56 (46.2%) occurred within 1 week of erenumab initiation, including 43 (35.5%) that occurred within 1 day. This rapid time to hypertension onset “is inconsistent with the pharmacokinetic profile of once-monthly erenumab 70 mg or 140 mg, which has a peak serum concentration in approximately 6 days,” said Dr. Dodick.
Hypertension ‘not a barrier’ to treatment
Commenting on the findings, Richard B. Lipton, MD, Edwin S. Lowe professor and vice chair of neurology at Albert Einstein College of Medicine, New York, noted that in theory blocking CGRP could increase blood pressure. However, he noted that the data and clinical experience do not suggest erenumab poses a serious risk.
“I have rarely seen new-onset hypertension with erenumab in the patients treated at our medical center. The few cases I have seen were in older adults with pre-existing hypertension,” he said.
The investigators’ review of clinical trial data together with global safety databases was a strength of their study, said Dr. Lipton. In clinical trials, patients are monitored carefully, and a placebo control group aids in the determination of background rates.
“In the trials, the incidence of new-onset hypertension or hypertension exacerbation was 0.9%, while the placebo rate was 0.2%,” said Dr. Lipton. “The absolute increase in the risk of hypertension was 0.6% or six cases per thousand: A low rate.” But clinical trials enroll carefully selected patients who do not represent the broad group of people treated with erenumab in clinical practice, he added.
The global safety data are more representative of patients who receive erenumab in real-world settings. The weaknesses of these data, though, are the lack of a control group and the incomplete ascertainment of data associated with spontaneous reporting.
Yet both types of studies, with their complementary strengths and weaknesses, indicated low rates of hypertension.
“The low incidence of hypertension, in my view, is not a barrier to the use of erenumab, though checking blood pressure after starting any new migraine therapy is prudent,” Dr. Lipton concluded.
The study was funded by Amgen. Dr. Dodick had no relevant disclosures. Dr. Lipton has consulted for and conducted studies funded by Amgen and by other companies that manufacture CGRP drugs. He has stock options in Biohaven.
A version of this article first appeared on Medscape.com.
FROM AHS 2021
Moving more, sitting less vital for migraine patients
according to a presentation at the American Headache Society’s 2021 annual meeting.
Though reliable research is sparse overall on how much physical activity people with migraine get, enough exists to reveal the need for clinicians to help patients identify ways to increase their levels of physical activity and make it a habit, said Dale S. Bond, PhD, a professor of psychiatry and human behavior at the Miriam Hospital and Brown University, both in Providence, R.I.
He emphasized the need not only to replace sedentary time with physical activity but also to reduce sedentary time overall.
“It’s important to note that because active and sedentary represent different behavioral domains, people can still be active – that is, achieving recommended levels of moderate to vigorous physical activity [MVPA] – but still be highly sedentary because they sit for long hours throughout the day,” Dr. Bond said. “This is important because MVPA will not necessarily eliminate the health risks of long hours of sitting.”
Dr. Bond reviewed the existing literature on physical activity and sedentary behavior among patients with migraine. His presentation, “Move More, Sit Less,” aimed at finding ways to incorporate more physical activity into the daily lives of those with migraine. Dr. Bond began by briefly reviewing the well-established benefits of physical activity, including healthy sleep; cardiovascular, respiratory, musculoskeletal, mental, and cognitive health; and metabolic functioning.
“Physical activity and exercise in particular enhances the functioning of bodily systems, including those that have direct relevance to migraine in its comorbidities,” Dr. Bond said. “The positive systemic effects of exercise on bodily systems carries potential to reduce migraine severity and related disability and morbidity.”
He also explained the ways in which excessive sedentary time can exacerbate migraine triggers. “Long periods of interrupted sitting elevated levels of glucose and fat in the bloodstream, which in turn triggers the immune system to attack the body via inflammation,” Dr. Bond said. “Low grade chronic inflammation has long been hypothesized to play a role in migraine pathogenesis.”
Recommended levels of exercise
The World Health Organization and the U.S. Department of Health & Human Services recommends at least 150-300 minutes of moderate-intensity aerobic physical activity or 75-150 minutes of vigorous activity each week. An additional recommendation is at least 2 days per week of muscle strengthening activities that involve all major muscle groups.
While neither of those organizations has specific guidelines on how much reduction of sedentary time is recommended, the Canadian Society for Exercise Physiology recommends limiting sedentary time to 8 or fewer hours per day.
Exercise and migraine
“Unfortunately, at present, we have very few studies from which to draw conclusions about the extent to which individuals with migraine adhere to physical activity and sedentary guidelines,” Dr. Bond said. Existing studies vary widely in sample types, study design, physical activity measure and MVPA outcome, including the type or definition of MVPA. “This wide variability in measures and outcomes makes it challenging to draw any conclusions about adherence to guidelines among individuals with migraine,” he said.
Existing evidence suggests anywhere from 32% to 66% of migraine patients are at least moderately active, though it’s not clear what constitutes “moderately active” behavior. It appears that activity levels of patients with migraine are low overall, but it’s less clear the extent to which these levels are lower than in controls given the paucity of evidence.
In one of the few studies using objective measures to assess physical activity in migraine patients, the daily level of MVPA was significantly lower in 25 women with migraine than in 25 age- and body mass index–matched women without migraine (P <. 003). Both groups had obesity. The same study found that virtually no women with migraine adhered to the guidelines recommending less than 8 hours a day of sedentary time, compared with 30% of women without migraine.
“Also, low physical activity and high sedentary levels appear to be consistent across headache and nonheadache days,” Dr. Bond said. “This finding in particular raises an interesting question: If migraine severity is not related to physical activity and sedentary time, what is it about migraine that contributes to an inactive and sedentary lifestyle?”
Dr. Bond noted that future research needs to include reports of frequency, duration, and intensity of activities performed as well as the percentage of participants who meet guidelines for physical activity and sedentary time. Ideally, these studies should include not only self-report but also objective measures of activity as well as assess sleep and identify barriers and facilitators to physical activity in patients.
Exercise avoidance
Dr. Bond described findings from survey of 100 women he conducted to better understand potential barriers and reported that 78% of patients report intentionally avoiding physical activity. These patients typically avoided it an average of 4 days per week, regardless of intensity, and additional survey findings found “that participants who reported any avoidance had stronger beliefs that physical activity would both trigger and worsen a migraine attack, compared with participants who reported no avoidance,” he said.
That finding matches the clinical experience of Jennifer Robblee, MD, MSc, assistant professor of neurology at Barrow Neurological Institute in Phoenix, who viewed the presentation but was not involved with it.
“They often feel that it is a trigger for worsening an attack or, for some people, can actually trigger an attack, and that they feel worse in the midst of an attack when they’re exercising,” Dr. Robblee said in an interview regarding her patients who exercise less frequently. “Since so many of the patients I see have a daily and constant headache, it’s about how they can get themselves to start to exercise when something makes them feel worse, even if it makes them feel better in the long run.”
Yet, experimental research suggests that physical activity is not necessarily a reliable trigger of migraine attacks and only worsens migraine in a minority of attacks, Dr. Bond said, revealing an interesting paradox: “While engaging in regular physical activity is an important migraine management strategy, most individuals in the study reported doing the exact opposite – that is, avoiding physical activity as a management strategy – and this strategy was associated with higher frequency and duration of attacks. Research from our group and others also suggested individuals with migraine could be overestimating the role that physical activity hasn’t triggering or worsening of attacks.”
Encouraging patients to exercise
Since the benefits of physical activity and limiting sedentary time outweigh the potential harms, “some physical activity is better than none,” Dr. Bond said. To help patients begin increasing their physical activity, he recommended advising them to start with small amounts and then gradually increase frequency, intensity, and duration over time.
Dr. Robblee follows a similar approach, taking into account each patient’s particular circumstances and any medications they’re taking, including the side effects of those medications.
“It’s about starting where they are,” Dr. Robblee said. “Some patients, despite having severe migraine, have built themselves up so they’re doing exercise three or four times per week, or every day, and I have other people who never exercise,” she said. “For those patients who are very sedentary, if I can get them to start with 5 minutes per week so they have that sense of accomplishment, then that’s where I start. Then slowly build it up over time. Like most things in the migraine world, I individualize it for the person.”
Dr. Bond offered the following specific tips to clinicians in educating and encouraging patients to increase physical activity:
- Educate patients regarding the short-and long-term benefits of moving more and sitting less, both for their migraines and for overall health.
- Correct misconceptions about the negative effects of physical activity as it relates to migraines.
- Personalize the rationale for physical activity to that patient’s specific values and personal goals.
- Encourage patients to use an activity tracker, both for tracking physical activity and sedentary time, and to monitor migraine attacks, stress, energy levels, and fatigue on days they do and do not exercise.
- Help patients set goals for eventually meeting MVPA recommendations and interrupting prolonged periods of sitting with brief movement breaks.
- Help patients identify rewards for meeting goals that are tied to the activity, such as new exercise clothing.
- Encourage patients to identify a consistent time for physical activity each day to establish a habit, “ideally in the morning before barriers and life get in the way,” he said.
Eventually, physical activity itself should become intrinsically rewarding, Dr. Bond said.
“To limit sitting and encourage more movement throughout the day, we want to make the choice to engage in physical activity easier by adding environmental cues that encourage physical activity,” he said. “Conversely, we want to make the choice to engage in sedentary behavior more difficult by increasing the amount of effort that is required to engage in these behaviors.”
Dr. Robblee found Dr. Bond’s emphasis on sitting less – distinct from moving more – a helpful frame to consider with her patients. “I really like the approach of looking at it from that approach: in addition to how do we get you up and moving, how much time are you sitting, and how often can you break that up into smaller increments so that you’re up more often?” Dr. Robblee said. “That sometimes sounds less scary than ‘let’s get you exercising.’ So ‘let’s get you sitting a little bit less.’ I think that is something I might start to adopt.”
No external funding was noted. Dr. Robblee is a principal investigator for a study sponsored by Eli Lilly and receives stipends for MedLink Neurology and Neurodiem. Dr. Bond reported no disclosures.
according to a presentation at the American Headache Society’s 2021 annual meeting.
Though reliable research is sparse overall on how much physical activity people with migraine get, enough exists to reveal the need for clinicians to help patients identify ways to increase their levels of physical activity and make it a habit, said Dale S. Bond, PhD, a professor of psychiatry and human behavior at the Miriam Hospital and Brown University, both in Providence, R.I.
He emphasized the need not only to replace sedentary time with physical activity but also to reduce sedentary time overall.
“It’s important to note that because active and sedentary represent different behavioral domains, people can still be active – that is, achieving recommended levels of moderate to vigorous physical activity [MVPA] – but still be highly sedentary because they sit for long hours throughout the day,” Dr. Bond said. “This is important because MVPA will not necessarily eliminate the health risks of long hours of sitting.”
Dr. Bond reviewed the existing literature on physical activity and sedentary behavior among patients with migraine. His presentation, “Move More, Sit Less,” aimed at finding ways to incorporate more physical activity into the daily lives of those with migraine. Dr. Bond began by briefly reviewing the well-established benefits of physical activity, including healthy sleep; cardiovascular, respiratory, musculoskeletal, mental, and cognitive health; and metabolic functioning.
“Physical activity and exercise in particular enhances the functioning of bodily systems, including those that have direct relevance to migraine in its comorbidities,” Dr. Bond said. “The positive systemic effects of exercise on bodily systems carries potential to reduce migraine severity and related disability and morbidity.”
He also explained the ways in which excessive sedentary time can exacerbate migraine triggers. “Long periods of interrupted sitting elevated levels of glucose and fat in the bloodstream, which in turn triggers the immune system to attack the body via inflammation,” Dr. Bond said. “Low grade chronic inflammation has long been hypothesized to play a role in migraine pathogenesis.”
Recommended levels of exercise
The World Health Organization and the U.S. Department of Health & Human Services recommends at least 150-300 minutes of moderate-intensity aerobic physical activity or 75-150 minutes of vigorous activity each week. An additional recommendation is at least 2 days per week of muscle strengthening activities that involve all major muscle groups.
While neither of those organizations has specific guidelines on how much reduction of sedentary time is recommended, the Canadian Society for Exercise Physiology recommends limiting sedentary time to 8 or fewer hours per day.
Exercise and migraine
“Unfortunately, at present, we have very few studies from which to draw conclusions about the extent to which individuals with migraine adhere to physical activity and sedentary guidelines,” Dr. Bond said. Existing studies vary widely in sample types, study design, physical activity measure and MVPA outcome, including the type or definition of MVPA. “This wide variability in measures and outcomes makes it challenging to draw any conclusions about adherence to guidelines among individuals with migraine,” he said.
Existing evidence suggests anywhere from 32% to 66% of migraine patients are at least moderately active, though it’s not clear what constitutes “moderately active” behavior. It appears that activity levels of patients with migraine are low overall, but it’s less clear the extent to which these levels are lower than in controls given the paucity of evidence.
In one of the few studies using objective measures to assess physical activity in migraine patients, the daily level of MVPA was significantly lower in 25 women with migraine than in 25 age- and body mass index–matched women without migraine (P <. 003). Both groups had obesity. The same study found that virtually no women with migraine adhered to the guidelines recommending less than 8 hours a day of sedentary time, compared with 30% of women without migraine.
“Also, low physical activity and high sedentary levels appear to be consistent across headache and nonheadache days,” Dr. Bond said. “This finding in particular raises an interesting question: If migraine severity is not related to physical activity and sedentary time, what is it about migraine that contributes to an inactive and sedentary lifestyle?”
Dr. Bond noted that future research needs to include reports of frequency, duration, and intensity of activities performed as well as the percentage of participants who meet guidelines for physical activity and sedentary time. Ideally, these studies should include not only self-report but also objective measures of activity as well as assess sleep and identify barriers and facilitators to physical activity in patients.
Exercise avoidance
Dr. Bond described findings from survey of 100 women he conducted to better understand potential barriers and reported that 78% of patients report intentionally avoiding physical activity. These patients typically avoided it an average of 4 days per week, regardless of intensity, and additional survey findings found “that participants who reported any avoidance had stronger beliefs that physical activity would both trigger and worsen a migraine attack, compared with participants who reported no avoidance,” he said.
That finding matches the clinical experience of Jennifer Robblee, MD, MSc, assistant professor of neurology at Barrow Neurological Institute in Phoenix, who viewed the presentation but was not involved with it.
“They often feel that it is a trigger for worsening an attack or, for some people, can actually trigger an attack, and that they feel worse in the midst of an attack when they’re exercising,” Dr. Robblee said in an interview regarding her patients who exercise less frequently. “Since so many of the patients I see have a daily and constant headache, it’s about how they can get themselves to start to exercise when something makes them feel worse, even if it makes them feel better in the long run.”
Yet, experimental research suggests that physical activity is not necessarily a reliable trigger of migraine attacks and only worsens migraine in a minority of attacks, Dr. Bond said, revealing an interesting paradox: “While engaging in regular physical activity is an important migraine management strategy, most individuals in the study reported doing the exact opposite – that is, avoiding physical activity as a management strategy – and this strategy was associated with higher frequency and duration of attacks. Research from our group and others also suggested individuals with migraine could be overestimating the role that physical activity hasn’t triggering or worsening of attacks.”
Encouraging patients to exercise
Since the benefits of physical activity and limiting sedentary time outweigh the potential harms, “some physical activity is better than none,” Dr. Bond said. To help patients begin increasing their physical activity, he recommended advising them to start with small amounts and then gradually increase frequency, intensity, and duration over time.
Dr. Robblee follows a similar approach, taking into account each patient’s particular circumstances and any medications they’re taking, including the side effects of those medications.
“It’s about starting where they are,” Dr. Robblee said. “Some patients, despite having severe migraine, have built themselves up so they’re doing exercise three or four times per week, or every day, and I have other people who never exercise,” she said. “For those patients who are very sedentary, if I can get them to start with 5 minutes per week so they have that sense of accomplishment, then that’s where I start. Then slowly build it up over time. Like most things in the migraine world, I individualize it for the person.”
Dr. Bond offered the following specific tips to clinicians in educating and encouraging patients to increase physical activity:
- Educate patients regarding the short-and long-term benefits of moving more and sitting less, both for their migraines and for overall health.
- Correct misconceptions about the negative effects of physical activity as it relates to migraines.
- Personalize the rationale for physical activity to that patient’s specific values and personal goals.
- Encourage patients to use an activity tracker, both for tracking physical activity and sedentary time, and to monitor migraine attacks, stress, energy levels, and fatigue on days they do and do not exercise.
- Help patients set goals for eventually meeting MVPA recommendations and interrupting prolonged periods of sitting with brief movement breaks.
- Help patients identify rewards for meeting goals that are tied to the activity, such as new exercise clothing.
- Encourage patients to identify a consistent time for physical activity each day to establish a habit, “ideally in the morning before barriers and life get in the way,” he said.
Eventually, physical activity itself should become intrinsically rewarding, Dr. Bond said.
“To limit sitting and encourage more movement throughout the day, we want to make the choice to engage in physical activity easier by adding environmental cues that encourage physical activity,” he said. “Conversely, we want to make the choice to engage in sedentary behavior more difficult by increasing the amount of effort that is required to engage in these behaviors.”
Dr. Robblee found Dr. Bond’s emphasis on sitting less – distinct from moving more – a helpful frame to consider with her patients. “I really like the approach of looking at it from that approach: in addition to how do we get you up and moving, how much time are you sitting, and how often can you break that up into smaller increments so that you’re up more often?” Dr. Robblee said. “That sometimes sounds less scary than ‘let’s get you exercising.’ So ‘let’s get you sitting a little bit less.’ I think that is something I might start to adopt.”
No external funding was noted. Dr. Robblee is a principal investigator for a study sponsored by Eli Lilly and receives stipends for MedLink Neurology and Neurodiem. Dr. Bond reported no disclosures.
according to a presentation at the American Headache Society’s 2021 annual meeting.
Though reliable research is sparse overall on how much physical activity people with migraine get, enough exists to reveal the need for clinicians to help patients identify ways to increase their levels of physical activity and make it a habit, said Dale S. Bond, PhD, a professor of psychiatry and human behavior at the Miriam Hospital and Brown University, both in Providence, R.I.
He emphasized the need not only to replace sedentary time with physical activity but also to reduce sedentary time overall.
“It’s important to note that because active and sedentary represent different behavioral domains, people can still be active – that is, achieving recommended levels of moderate to vigorous physical activity [MVPA] – but still be highly sedentary because they sit for long hours throughout the day,” Dr. Bond said. “This is important because MVPA will not necessarily eliminate the health risks of long hours of sitting.”
Dr. Bond reviewed the existing literature on physical activity and sedentary behavior among patients with migraine. His presentation, “Move More, Sit Less,” aimed at finding ways to incorporate more physical activity into the daily lives of those with migraine. Dr. Bond began by briefly reviewing the well-established benefits of physical activity, including healthy sleep; cardiovascular, respiratory, musculoskeletal, mental, and cognitive health; and metabolic functioning.
“Physical activity and exercise in particular enhances the functioning of bodily systems, including those that have direct relevance to migraine in its comorbidities,” Dr. Bond said. “The positive systemic effects of exercise on bodily systems carries potential to reduce migraine severity and related disability and morbidity.”
He also explained the ways in which excessive sedentary time can exacerbate migraine triggers. “Long periods of interrupted sitting elevated levels of glucose and fat in the bloodstream, which in turn triggers the immune system to attack the body via inflammation,” Dr. Bond said. “Low grade chronic inflammation has long been hypothesized to play a role in migraine pathogenesis.”
Recommended levels of exercise
The World Health Organization and the U.S. Department of Health & Human Services recommends at least 150-300 minutes of moderate-intensity aerobic physical activity or 75-150 minutes of vigorous activity each week. An additional recommendation is at least 2 days per week of muscle strengthening activities that involve all major muscle groups.
While neither of those organizations has specific guidelines on how much reduction of sedentary time is recommended, the Canadian Society for Exercise Physiology recommends limiting sedentary time to 8 or fewer hours per day.
Exercise and migraine
“Unfortunately, at present, we have very few studies from which to draw conclusions about the extent to which individuals with migraine adhere to physical activity and sedentary guidelines,” Dr. Bond said. Existing studies vary widely in sample types, study design, physical activity measure and MVPA outcome, including the type or definition of MVPA. “This wide variability in measures and outcomes makes it challenging to draw any conclusions about adherence to guidelines among individuals with migraine,” he said.
Existing evidence suggests anywhere from 32% to 66% of migraine patients are at least moderately active, though it’s not clear what constitutes “moderately active” behavior. It appears that activity levels of patients with migraine are low overall, but it’s less clear the extent to which these levels are lower than in controls given the paucity of evidence.
In one of the few studies using objective measures to assess physical activity in migraine patients, the daily level of MVPA was significantly lower in 25 women with migraine than in 25 age- and body mass index–matched women without migraine (P <. 003). Both groups had obesity. The same study found that virtually no women with migraine adhered to the guidelines recommending less than 8 hours a day of sedentary time, compared with 30% of women without migraine.
“Also, low physical activity and high sedentary levels appear to be consistent across headache and nonheadache days,” Dr. Bond said. “This finding in particular raises an interesting question: If migraine severity is not related to physical activity and sedentary time, what is it about migraine that contributes to an inactive and sedentary lifestyle?”
Dr. Bond noted that future research needs to include reports of frequency, duration, and intensity of activities performed as well as the percentage of participants who meet guidelines for physical activity and sedentary time. Ideally, these studies should include not only self-report but also objective measures of activity as well as assess sleep and identify barriers and facilitators to physical activity in patients.
Exercise avoidance
Dr. Bond described findings from survey of 100 women he conducted to better understand potential barriers and reported that 78% of patients report intentionally avoiding physical activity. These patients typically avoided it an average of 4 days per week, regardless of intensity, and additional survey findings found “that participants who reported any avoidance had stronger beliefs that physical activity would both trigger and worsen a migraine attack, compared with participants who reported no avoidance,” he said.
That finding matches the clinical experience of Jennifer Robblee, MD, MSc, assistant professor of neurology at Barrow Neurological Institute in Phoenix, who viewed the presentation but was not involved with it.
“They often feel that it is a trigger for worsening an attack or, for some people, can actually trigger an attack, and that they feel worse in the midst of an attack when they’re exercising,” Dr. Robblee said in an interview regarding her patients who exercise less frequently. “Since so many of the patients I see have a daily and constant headache, it’s about how they can get themselves to start to exercise when something makes them feel worse, even if it makes them feel better in the long run.”
Yet, experimental research suggests that physical activity is not necessarily a reliable trigger of migraine attacks and only worsens migraine in a minority of attacks, Dr. Bond said, revealing an interesting paradox: “While engaging in regular physical activity is an important migraine management strategy, most individuals in the study reported doing the exact opposite – that is, avoiding physical activity as a management strategy – and this strategy was associated with higher frequency and duration of attacks. Research from our group and others also suggested individuals with migraine could be overestimating the role that physical activity hasn’t triggering or worsening of attacks.”
Encouraging patients to exercise
Since the benefits of physical activity and limiting sedentary time outweigh the potential harms, “some physical activity is better than none,” Dr. Bond said. To help patients begin increasing their physical activity, he recommended advising them to start with small amounts and then gradually increase frequency, intensity, and duration over time.
Dr. Robblee follows a similar approach, taking into account each patient’s particular circumstances and any medications they’re taking, including the side effects of those medications.
“It’s about starting where they are,” Dr. Robblee said. “Some patients, despite having severe migraine, have built themselves up so they’re doing exercise three or four times per week, or every day, and I have other people who never exercise,” she said. “For those patients who are very sedentary, if I can get them to start with 5 minutes per week so they have that sense of accomplishment, then that’s where I start. Then slowly build it up over time. Like most things in the migraine world, I individualize it for the person.”
Dr. Bond offered the following specific tips to clinicians in educating and encouraging patients to increase physical activity:
- Educate patients regarding the short-and long-term benefits of moving more and sitting less, both for their migraines and for overall health.
- Correct misconceptions about the negative effects of physical activity as it relates to migraines.
- Personalize the rationale for physical activity to that patient’s specific values and personal goals.
- Encourage patients to use an activity tracker, both for tracking physical activity and sedentary time, and to monitor migraine attacks, stress, energy levels, and fatigue on days they do and do not exercise.
- Help patients set goals for eventually meeting MVPA recommendations and interrupting prolonged periods of sitting with brief movement breaks.
- Help patients identify rewards for meeting goals that are tied to the activity, such as new exercise clothing.
- Encourage patients to identify a consistent time for physical activity each day to establish a habit, “ideally in the morning before barriers and life get in the way,” he said.
Eventually, physical activity itself should become intrinsically rewarding, Dr. Bond said.
“To limit sitting and encourage more movement throughout the day, we want to make the choice to engage in physical activity easier by adding environmental cues that encourage physical activity,” he said. “Conversely, we want to make the choice to engage in sedentary behavior more difficult by increasing the amount of effort that is required to engage in these behaviors.”
Dr. Robblee found Dr. Bond’s emphasis on sitting less – distinct from moving more – a helpful frame to consider with her patients. “I really like the approach of looking at it from that approach: in addition to how do we get you up and moving, how much time are you sitting, and how often can you break that up into smaller increments so that you’re up more often?” Dr. Robblee said. “That sometimes sounds less scary than ‘let’s get you exercising.’ So ‘let’s get you sitting a little bit less.’ I think that is something I might start to adopt.”
No external funding was noted. Dr. Robblee is a principal investigator for a study sponsored by Eli Lilly and receives stipends for MedLink Neurology and Neurodiem. Dr. Bond reported no disclosures.
FROM AHS 2021
Ubrogepant effective for acute migraine even with preventive monoclonal antibody therapy
according to preliminary findings presented at the American Headache Society’s 2021 annual meeting.
“Because prevention [with mAbs] is rarely 100% effective, virtually everyone on preventive treatment needs to also take acute treatment,” presenter Richard B. Lipton, MD, a professor of neurology and director of the Montefiore Headache Center at Albert Einstein College of Medicine, New York, said in an interview after his presentation. He explained that ubrogepant, a small-molecule CGRP receptor blocker, is approved for acute treatment of migraine, while mAbs, which block the CGRP receptor or CGRP itself, are approved for prevention. “Many people predicted that gepants would not work in people on CGRP-targeted mAbs because of overlapping mechanisms.”
Dr. Lipton himself was not surprised by the findings, however. “For me, the surprise was that ubrogepant worked so well,” he said.
Novel data collection
Uniquely, his study used an entirely remote design with mobile applications to safely evaluate the drug’s real-world effectiveness in the midst of the COVID-19 pandemic. The prospective, observational study used the mobile app Migraine Buddy to collect data and assess outcomes from the use of 50 mg or 100 mg of ubrogepant along with a mAb, onabotA, or both.
In most migraine trials, researchers ask patients to track their symptoms in electronic diaries they learn how to use in the clinic.
“One disadvantage of this approach is that people usually need to carry two devices, the study device and their smartphone,” Dr. Lipton said in an interview. “In this study, people download an app at home to their smartphone and only need to carry one device. Though remote studies are particularly valuable in the time of pandemic, I believe that apps like Migraine Buddy are and will remain a valuable tool for addressing many research questions.”
Jennifer Robblee, MD, MSc, an assistant professor of neurology at Barrow Neurological Institute in Phoenix, viewed the presentation and was also impressed with the novel use of a smartphone app to conduct the study. “I think that was a unique and cool demonstration of what can be done with the apps out there now,” Dr. Robblee said in an interview. “If you want to have really good tracking and more through tracking, apps like this are fabulous and are very patient forward and patient friendly.”
Combination therapy
The researchers invited 4,541 adults to participate in the study if they had previously reported at least three migraine attacks in the past 30 days and if they had treated at least three prior attacks with ubrogepant. The 483 participants who enrolled after consent and screening included 272 taking ubrogepant with mAb, 132 participants taking ubrogepant with onabotA, and 79 taking ubrogepant with both onabotA and mAb.
For 30 days, participants reported in the app’s diary their pain relief and the time elapsed since taking ubrogepant until they returned to normal functioning. Endpoints included meaningful pain relief – defined as “a level of pain relief that is meaningful to you” – and return to normal function at 2 and 4 hours.
During the study, 352 participants reported treating a migraine attack with a single dose of ubrogepant, and 78 participants treated migraine with two doses. The former group included 193 patients in the ubrogepant plus mAb group, 102 patients in the ubrogepant plus onabotA group, and 57 patients in the ubrogepant plus both group. Because of the limited enrollment in the second two arms, the data Dr. Lipton presented data only on the ubrogepant with mAb arm.
Most of this group (89.1%) was female, with an average age of 40 years and an average Migraine Disability Assessment score of 72.2. Most of the patients were taking erenumab (44.6%) or galcanezumab (34.2%) with the remaining patients taking fremanezumab (17.6%), eptinezumab (3.1%) or multiple mAbs (0.5%). Most participants (59.6%) were prescribed 100-mg ubrogepant dose while the remaining participants took 50 mg.
The analysis of the ubrogepant plus mAb group revealed that 64.2% of patients reported meaningful pain relief at 2 hours, and 84.5% had meaningful pain relief 4 hours after taking ubrogepant. The odds of achieving meaningful pain relief were statistically significant at both time points and remained significant after adjustment for participants’ age, Migraine Disability Assessment score and self-reported prescribed ubrogepant dose (P < .001).
“This study shows that in patients with migraine on CGRP-targeted monoclonal antibodies, ubrogepant is an acute treatment to consider for breakthrough headaches,” Dr. Lipton said. He added that they have now completed the study with more participants and begun analyzing all three groups.
“Full analyses will include data from multiple attacks, attacks treated with a second dose of ubrogepant, additional daily and 30-day effectiveness measures for use of ubrogepant with onabotA and use of ubrogepant with both onabotA and CGRP mAbs,” Dr. Lipton said.
While the findings did not surprise Dr. Robblee, she was happy to see a study that explicitly testing the combination of these treatments, especially given access challenges. “Right now, because treatments are new, we get a lot of insurance denials,” Dr. Robblee said in an interview. “It’s great to have a study out there that we can turn to and say, ‘hey, look, they had all these patients safely using these together.’ It’s going to help us improve access for patients.”
Though Dr. Robblee typically uses old-school pen-and-calendar diaries with her patients, she also sees potential for the use of apps going forward, just as she sees for virtual health care.
“I’ve found telemedicine in general to be a really great addition to the migraine world, and this plays into our ability to use telemedicine paired with tracking,” Dr. Robblee said. “In so many studies, we’re doing a diary anyway, so if there are standard diaries and programs we’re all using, that would be a nice way to do these.”
She notes that most symptom tracking for pain is subjective already, and these apps often include the options to print out the data or to export or transfer it electronically to physicians. “It’s giving us meaningful data,” she said.
The research was funded by AbbVie. Dr. Lipton has received honoraria or research support from AbbVie, Amgen, Biohaven, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva, Vector and Vedanta Research. He holds stock options in Biohaven and Ctrl M. Dr. Robblee is a principal investigator for a study sponsored by Eli Lilly and receives stipends for MedLink Neurology and Neurodiem.
according to preliminary findings presented at the American Headache Society’s 2021 annual meeting.
“Because prevention [with mAbs] is rarely 100% effective, virtually everyone on preventive treatment needs to also take acute treatment,” presenter Richard B. Lipton, MD, a professor of neurology and director of the Montefiore Headache Center at Albert Einstein College of Medicine, New York, said in an interview after his presentation. He explained that ubrogepant, a small-molecule CGRP receptor blocker, is approved for acute treatment of migraine, while mAbs, which block the CGRP receptor or CGRP itself, are approved for prevention. “Many people predicted that gepants would not work in people on CGRP-targeted mAbs because of overlapping mechanisms.”
Dr. Lipton himself was not surprised by the findings, however. “For me, the surprise was that ubrogepant worked so well,” he said.
Novel data collection
Uniquely, his study used an entirely remote design with mobile applications to safely evaluate the drug’s real-world effectiveness in the midst of the COVID-19 pandemic. The prospective, observational study used the mobile app Migraine Buddy to collect data and assess outcomes from the use of 50 mg or 100 mg of ubrogepant along with a mAb, onabotA, or both.
In most migraine trials, researchers ask patients to track their symptoms in electronic diaries they learn how to use in the clinic.
“One disadvantage of this approach is that people usually need to carry two devices, the study device and their smartphone,” Dr. Lipton said in an interview. “In this study, people download an app at home to their smartphone and only need to carry one device. Though remote studies are particularly valuable in the time of pandemic, I believe that apps like Migraine Buddy are and will remain a valuable tool for addressing many research questions.”
Jennifer Robblee, MD, MSc, an assistant professor of neurology at Barrow Neurological Institute in Phoenix, viewed the presentation and was also impressed with the novel use of a smartphone app to conduct the study. “I think that was a unique and cool demonstration of what can be done with the apps out there now,” Dr. Robblee said in an interview. “If you want to have really good tracking and more through tracking, apps like this are fabulous and are very patient forward and patient friendly.”
Combination therapy
The researchers invited 4,541 adults to participate in the study if they had previously reported at least three migraine attacks in the past 30 days and if they had treated at least three prior attacks with ubrogepant. The 483 participants who enrolled after consent and screening included 272 taking ubrogepant with mAb, 132 participants taking ubrogepant with onabotA, and 79 taking ubrogepant with both onabotA and mAb.
For 30 days, participants reported in the app’s diary their pain relief and the time elapsed since taking ubrogepant until they returned to normal functioning. Endpoints included meaningful pain relief – defined as “a level of pain relief that is meaningful to you” – and return to normal function at 2 and 4 hours.
During the study, 352 participants reported treating a migraine attack with a single dose of ubrogepant, and 78 participants treated migraine with two doses. The former group included 193 patients in the ubrogepant plus mAb group, 102 patients in the ubrogepant plus onabotA group, and 57 patients in the ubrogepant plus both group. Because of the limited enrollment in the second two arms, the data Dr. Lipton presented data only on the ubrogepant with mAb arm.
Most of this group (89.1%) was female, with an average age of 40 years and an average Migraine Disability Assessment score of 72.2. Most of the patients were taking erenumab (44.6%) or galcanezumab (34.2%) with the remaining patients taking fremanezumab (17.6%), eptinezumab (3.1%) or multiple mAbs (0.5%). Most participants (59.6%) were prescribed 100-mg ubrogepant dose while the remaining participants took 50 mg.
The analysis of the ubrogepant plus mAb group revealed that 64.2% of patients reported meaningful pain relief at 2 hours, and 84.5% had meaningful pain relief 4 hours after taking ubrogepant. The odds of achieving meaningful pain relief were statistically significant at both time points and remained significant after adjustment for participants’ age, Migraine Disability Assessment score and self-reported prescribed ubrogepant dose (P < .001).
“This study shows that in patients with migraine on CGRP-targeted monoclonal antibodies, ubrogepant is an acute treatment to consider for breakthrough headaches,” Dr. Lipton said. He added that they have now completed the study with more participants and begun analyzing all three groups.
“Full analyses will include data from multiple attacks, attacks treated with a second dose of ubrogepant, additional daily and 30-day effectiveness measures for use of ubrogepant with onabotA and use of ubrogepant with both onabotA and CGRP mAbs,” Dr. Lipton said.
While the findings did not surprise Dr. Robblee, she was happy to see a study that explicitly testing the combination of these treatments, especially given access challenges. “Right now, because treatments are new, we get a lot of insurance denials,” Dr. Robblee said in an interview. “It’s great to have a study out there that we can turn to and say, ‘hey, look, they had all these patients safely using these together.’ It’s going to help us improve access for patients.”
Though Dr. Robblee typically uses old-school pen-and-calendar diaries with her patients, she also sees potential for the use of apps going forward, just as she sees for virtual health care.
“I’ve found telemedicine in general to be a really great addition to the migraine world, and this plays into our ability to use telemedicine paired with tracking,” Dr. Robblee said. “In so many studies, we’re doing a diary anyway, so if there are standard diaries and programs we’re all using, that would be a nice way to do these.”
She notes that most symptom tracking for pain is subjective already, and these apps often include the options to print out the data or to export or transfer it electronically to physicians. “It’s giving us meaningful data,” she said.
The research was funded by AbbVie. Dr. Lipton has received honoraria or research support from AbbVie, Amgen, Biohaven, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva, Vector and Vedanta Research. He holds stock options in Biohaven and Ctrl M. Dr. Robblee is a principal investigator for a study sponsored by Eli Lilly and receives stipends for MedLink Neurology and Neurodiem.
according to preliminary findings presented at the American Headache Society’s 2021 annual meeting.
“Because prevention [with mAbs] is rarely 100% effective, virtually everyone on preventive treatment needs to also take acute treatment,” presenter Richard B. Lipton, MD, a professor of neurology and director of the Montefiore Headache Center at Albert Einstein College of Medicine, New York, said in an interview after his presentation. He explained that ubrogepant, a small-molecule CGRP receptor blocker, is approved for acute treatment of migraine, while mAbs, which block the CGRP receptor or CGRP itself, are approved for prevention. “Many people predicted that gepants would not work in people on CGRP-targeted mAbs because of overlapping mechanisms.”
Dr. Lipton himself was not surprised by the findings, however. “For me, the surprise was that ubrogepant worked so well,” he said.
Novel data collection
Uniquely, his study used an entirely remote design with mobile applications to safely evaluate the drug’s real-world effectiveness in the midst of the COVID-19 pandemic. The prospective, observational study used the mobile app Migraine Buddy to collect data and assess outcomes from the use of 50 mg or 100 mg of ubrogepant along with a mAb, onabotA, or both.
In most migraine trials, researchers ask patients to track their symptoms in electronic diaries they learn how to use in the clinic.
“One disadvantage of this approach is that people usually need to carry two devices, the study device and their smartphone,” Dr. Lipton said in an interview. “In this study, people download an app at home to their smartphone and only need to carry one device. Though remote studies are particularly valuable in the time of pandemic, I believe that apps like Migraine Buddy are and will remain a valuable tool for addressing many research questions.”
Jennifer Robblee, MD, MSc, an assistant professor of neurology at Barrow Neurological Institute in Phoenix, viewed the presentation and was also impressed with the novel use of a smartphone app to conduct the study. “I think that was a unique and cool demonstration of what can be done with the apps out there now,” Dr. Robblee said in an interview. “If you want to have really good tracking and more through tracking, apps like this are fabulous and are very patient forward and patient friendly.”
Combination therapy
The researchers invited 4,541 adults to participate in the study if they had previously reported at least three migraine attacks in the past 30 days and if they had treated at least three prior attacks with ubrogepant. The 483 participants who enrolled after consent and screening included 272 taking ubrogepant with mAb, 132 participants taking ubrogepant with onabotA, and 79 taking ubrogepant with both onabotA and mAb.
For 30 days, participants reported in the app’s diary their pain relief and the time elapsed since taking ubrogepant until they returned to normal functioning. Endpoints included meaningful pain relief – defined as “a level of pain relief that is meaningful to you” – and return to normal function at 2 and 4 hours.
During the study, 352 participants reported treating a migraine attack with a single dose of ubrogepant, and 78 participants treated migraine with two doses. The former group included 193 patients in the ubrogepant plus mAb group, 102 patients in the ubrogepant plus onabotA group, and 57 patients in the ubrogepant plus both group. Because of the limited enrollment in the second two arms, the data Dr. Lipton presented data only on the ubrogepant with mAb arm.
Most of this group (89.1%) was female, with an average age of 40 years and an average Migraine Disability Assessment score of 72.2. Most of the patients were taking erenumab (44.6%) or galcanezumab (34.2%) with the remaining patients taking fremanezumab (17.6%), eptinezumab (3.1%) or multiple mAbs (0.5%). Most participants (59.6%) were prescribed 100-mg ubrogepant dose while the remaining participants took 50 mg.
The analysis of the ubrogepant plus mAb group revealed that 64.2% of patients reported meaningful pain relief at 2 hours, and 84.5% had meaningful pain relief 4 hours after taking ubrogepant. The odds of achieving meaningful pain relief were statistically significant at both time points and remained significant after adjustment for participants’ age, Migraine Disability Assessment score and self-reported prescribed ubrogepant dose (P < .001).
“This study shows that in patients with migraine on CGRP-targeted monoclonal antibodies, ubrogepant is an acute treatment to consider for breakthrough headaches,” Dr. Lipton said. He added that they have now completed the study with more participants and begun analyzing all three groups.
“Full analyses will include data from multiple attacks, attacks treated with a second dose of ubrogepant, additional daily and 30-day effectiveness measures for use of ubrogepant with onabotA and use of ubrogepant with both onabotA and CGRP mAbs,” Dr. Lipton said.
While the findings did not surprise Dr. Robblee, she was happy to see a study that explicitly testing the combination of these treatments, especially given access challenges. “Right now, because treatments are new, we get a lot of insurance denials,” Dr. Robblee said in an interview. “It’s great to have a study out there that we can turn to and say, ‘hey, look, they had all these patients safely using these together.’ It’s going to help us improve access for patients.”
Though Dr. Robblee typically uses old-school pen-and-calendar diaries with her patients, she also sees potential for the use of apps going forward, just as she sees for virtual health care.
“I’ve found telemedicine in general to be a really great addition to the migraine world, and this plays into our ability to use telemedicine paired with tracking,” Dr. Robblee said. “In so many studies, we’re doing a diary anyway, so if there are standard diaries and programs we’re all using, that would be a nice way to do these.”
She notes that most symptom tracking for pain is subjective already, and these apps often include the options to print out the data or to export or transfer it electronically to physicians. “It’s giving us meaningful data,” she said.
The research was funded by AbbVie. Dr. Lipton has received honoraria or research support from AbbVie, Amgen, Biohaven, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva, Vector and Vedanta Research. He holds stock options in Biohaven and Ctrl M. Dr. Robblee is a principal investigator for a study sponsored by Eli Lilly and receives stipends for MedLink Neurology and Neurodiem.
FROM AHS 2021
Migraine linked to more COVID-19 infections, symptoms but less health care utilization
, according to a study presented at the American Headache Society’s 2021 annual meeting.
“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”
In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.
Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.
Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.
For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).
The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).
Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).
Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:
- Difficulty breathing or shortness of breath (P = .005).
- Fever.
- Headache, sore throat, and/or congestion.
- Fatigue.
- Loss of smell and taste.
- Chills and body aches.
- Persistent pain or pressure in the chest.
- Confusion or inability to arouse.
- Digestive issues (P = .005).
- Bluish lips or face.
For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
Changes in health care utilization
“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.
Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).
Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”
Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.
Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.
“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”
The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.
, according to a study presented at the American Headache Society’s 2021 annual meeting.
“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”
In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.
Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.
Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.
For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).
The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).
Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).
Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:
- Difficulty breathing or shortness of breath (P = .005).
- Fever.
- Headache, sore throat, and/or congestion.
- Fatigue.
- Loss of smell and taste.
- Chills and body aches.
- Persistent pain or pressure in the chest.
- Confusion or inability to arouse.
- Digestive issues (P = .005).
- Bluish lips or face.
For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
Changes in health care utilization
“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.
Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).
Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”
Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.
Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.
“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”
The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.
, according to a study presented at the American Headache Society’s 2021 annual meeting.
“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”
In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.
Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.
Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.
For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).
The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).
Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).
Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:
- Difficulty breathing or shortness of breath (P = .005).
- Fever.
- Headache, sore throat, and/or congestion.
- Fatigue.
- Loss of smell and taste.
- Chills and body aches.
- Persistent pain or pressure in the chest.
- Confusion or inability to arouse.
- Digestive issues (P = .005).
- Bluish lips or face.
For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
Changes in health care utilization
“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.
Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).
Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”
Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.
Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.
“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”
The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.
FROM AHS 2021
Chronic headache pain in veterans linked to suicide attempts
, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).
“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
‘Surprising’ findings
“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.
“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
Veterans with chronic pain
The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.
The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.
The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.
Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.
More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).
“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”
The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).
The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.
Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.
Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.
“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”
No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.
, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).
“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
‘Surprising’ findings
“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.
“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
Veterans with chronic pain
The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.
The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.
The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.
Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.
More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).
“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”
The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).
The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.
Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.
Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.
“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”
No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.
, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).
“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
‘Surprising’ findings
“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.
“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
Veterans with chronic pain
The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.
The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.
The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.
Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.
More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).
“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”
The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).
The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.
Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.
Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.
“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”
No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.
FROM AHS 2021
e-TNS device passes at-home test
The study also demonstrated that the device, manufactured by Cefaly and cleared in 2020 by the Food and Drug Administration for over-the-counter use, can be safely and effectively used at home.
The study also explored the benefits of 2 hours of use, rather than the 1 hour of use tested in a previous study. “The programming on the device is currently [set to] turn off at 1 hour. As a result of this study, I tell patients if they don’t have adequate relief, and they’re tolerating it, that they can activate it again for a second hour,” Stewart Tepper, MD, said in an interview. Dr. Tepper is a professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., and a coauthor of the study that was presented by Deena Kuruvilla, MD, at the American Headache Society’s 2021 annual meeting. Dr. Kuruvilla is a neurologist and director of the Westport (Conn.) Headache Institute.
The improvements seen over the sham were significant but not overwhelming, according to Deborah Friedman, MD, MPH, professor of neurology and ophthalmology at the University of Texas, Dallas.
“The numbers are not super impressive when you compare them with other devices. I thought it was interesting that the most bothersome symptom went away in a much higher percentage of people than the headache. That was actually pretty impressive,” said Dr. Friedman, who was asked to comment on the study. She also wondered if the sham device may have inadvertently provided a small amount of stimulation, which could explain the smaller than expected efficacy difference. “It just kind of makes me wonder because I would expect to see a larger separation, even though it was statistically significant.”
The study was an overall success according to Dr. Tepper, who noted that the efficacy of pain freedom was comparable with what has been seen with calcitonin gene-related peptide receptor antagonists (gepants), as well as relieving the most bothersome symptom at 2 hours. The device failed to reduce the usage of rescue medication, suggesting that it might be a candidate to combine with rescue medications. “I think the main thing is it works. It works in a sham-controlled trial, it works at home, and it works comparably to acute medication. And it is further evidence that the lack of access is something that needs to be addressed,” said Dr. Tepper.
Access will depend on insurance companies, who have so far been reluctant to pay for the device. Dr. Tepper is not optimistic they will come around on their own. “My feeling about it is that the only way that payers will finally start to cover this is with a concerted, organized advocacy campaign by patients. The analogy is that when the disease-modifying therapies became available for multiple sclerosis, the National MS Society organized the MS patients and they demanded that the payers cover the disease modifying therapies. That’s the kind of intense focus of advocacy that needs to be done for these noninvasive neuromodulation devices,” said Dr. Tepper.
The TEAM study was a double blind, randomized, sham-controlled trial of 538 patients who were asked to use neurostimulation for a 2-hour, continuous session within 4 hours of a moderate to severe migraine accompanied by at least one migraine-associated symptom. At 2 hours, 25.5% of those using the device achieved pain freedom, compared with 18.3% of those using the sham (P < .05). Among those using the device, 56.4% had freedom from most bothersome symptom, compared with 42.3% of those using the sham (P < .01).
Pain relief at 2 hours was more common in the device group (69.5% vs. 55.2%; P < .01), as was absence of all migraine-associated symptoms at 2 hours (42.5% vs. 34.1%; P < .05), sustained pain freedom at 24 hours (22.8% vs. 15.8%; P < .05), and sustained pain relief at 24 hours (45.9% vs. 34.4%; P < .01). There was no statistically significant between-group difference in use of rescue medications.
In the device group, 8.5% of patients experienced an adverse event, versus 2.9% in the sham group (P = .004). The only adverse reaction that occurred more frequently in the device group was forehead paresthesia, discomfort, and burning (3.5% vs. 0.4%; P = .009).
The study was funded by Cefaly. Dr. Tepper and Dr. Friedman have no relevant financial disclosures.
The study also demonstrated that the device, manufactured by Cefaly and cleared in 2020 by the Food and Drug Administration for over-the-counter use, can be safely and effectively used at home.
The study also explored the benefits of 2 hours of use, rather than the 1 hour of use tested in a previous study. “The programming on the device is currently [set to] turn off at 1 hour. As a result of this study, I tell patients if they don’t have adequate relief, and they’re tolerating it, that they can activate it again for a second hour,” Stewart Tepper, MD, said in an interview. Dr. Tepper is a professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., and a coauthor of the study that was presented by Deena Kuruvilla, MD, at the American Headache Society’s 2021 annual meeting. Dr. Kuruvilla is a neurologist and director of the Westport (Conn.) Headache Institute.
The improvements seen over the sham were significant but not overwhelming, according to Deborah Friedman, MD, MPH, professor of neurology and ophthalmology at the University of Texas, Dallas.
“The numbers are not super impressive when you compare them with other devices. I thought it was interesting that the most bothersome symptom went away in a much higher percentage of people than the headache. That was actually pretty impressive,” said Dr. Friedman, who was asked to comment on the study. She also wondered if the sham device may have inadvertently provided a small amount of stimulation, which could explain the smaller than expected efficacy difference. “It just kind of makes me wonder because I would expect to see a larger separation, even though it was statistically significant.”
The study was an overall success according to Dr. Tepper, who noted that the efficacy of pain freedom was comparable with what has been seen with calcitonin gene-related peptide receptor antagonists (gepants), as well as relieving the most bothersome symptom at 2 hours. The device failed to reduce the usage of rescue medication, suggesting that it might be a candidate to combine with rescue medications. “I think the main thing is it works. It works in a sham-controlled trial, it works at home, and it works comparably to acute medication. And it is further evidence that the lack of access is something that needs to be addressed,” said Dr. Tepper.
Access will depend on insurance companies, who have so far been reluctant to pay for the device. Dr. Tepper is not optimistic they will come around on their own. “My feeling about it is that the only way that payers will finally start to cover this is with a concerted, organized advocacy campaign by patients. The analogy is that when the disease-modifying therapies became available for multiple sclerosis, the National MS Society organized the MS patients and they demanded that the payers cover the disease modifying therapies. That’s the kind of intense focus of advocacy that needs to be done for these noninvasive neuromodulation devices,” said Dr. Tepper.
The TEAM study was a double blind, randomized, sham-controlled trial of 538 patients who were asked to use neurostimulation for a 2-hour, continuous session within 4 hours of a moderate to severe migraine accompanied by at least one migraine-associated symptom. At 2 hours, 25.5% of those using the device achieved pain freedom, compared with 18.3% of those using the sham (P < .05). Among those using the device, 56.4% had freedom from most bothersome symptom, compared with 42.3% of those using the sham (P < .01).
Pain relief at 2 hours was more common in the device group (69.5% vs. 55.2%; P < .01), as was absence of all migraine-associated symptoms at 2 hours (42.5% vs. 34.1%; P < .05), sustained pain freedom at 24 hours (22.8% vs. 15.8%; P < .05), and sustained pain relief at 24 hours (45.9% vs. 34.4%; P < .01). There was no statistically significant between-group difference in use of rescue medications.
In the device group, 8.5% of patients experienced an adverse event, versus 2.9% in the sham group (P = .004). The only adverse reaction that occurred more frequently in the device group was forehead paresthesia, discomfort, and burning (3.5% vs. 0.4%; P = .009).
The study was funded by Cefaly. Dr. Tepper and Dr. Friedman have no relevant financial disclosures.
The study also demonstrated that the device, manufactured by Cefaly and cleared in 2020 by the Food and Drug Administration for over-the-counter use, can be safely and effectively used at home.
The study also explored the benefits of 2 hours of use, rather than the 1 hour of use tested in a previous study. “The programming on the device is currently [set to] turn off at 1 hour. As a result of this study, I tell patients if they don’t have adequate relief, and they’re tolerating it, that they can activate it again for a second hour,” Stewart Tepper, MD, said in an interview. Dr. Tepper is a professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., and a coauthor of the study that was presented by Deena Kuruvilla, MD, at the American Headache Society’s 2021 annual meeting. Dr. Kuruvilla is a neurologist and director of the Westport (Conn.) Headache Institute.
The improvements seen over the sham were significant but not overwhelming, according to Deborah Friedman, MD, MPH, professor of neurology and ophthalmology at the University of Texas, Dallas.
“The numbers are not super impressive when you compare them with other devices. I thought it was interesting that the most bothersome symptom went away in a much higher percentage of people than the headache. That was actually pretty impressive,” said Dr. Friedman, who was asked to comment on the study. She also wondered if the sham device may have inadvertently provided a small amount of stimulation, which could explain the smaller than expected efficacy difference. “It just kind of makes me wonder because I would expect to see a larger separation, even though it was statistically significant.”
The study was an overall success according to Dr. Tepper, who noted that the efficacy of pain freedom was comparable with what has been seen with calcitonin gene-related peptide receptor antagonists (gepants), as well as relieving the most bothersome symptom at 2 hours. The device failed to reduce the usage of rescue medication, suggesting that it might be a candidate to combine with rescue medications. “I think the main thing is it works. It works in a sham-controlled trial, it works at home, and it works comparably to acute medication. And it is further evidence that the lack of access is something that needs to be addressed,” said Dr. Tepper.
Access will depend on insurance companies, who have so far been reluctant to pay for the device. Dr. Tepper is not optimistic they will come around on their own. “My feeling about it is that the only way that payers will finally start to cover this is with a concerted, organized advocacy campaign by patients. The analogy is that when the disease-modifying therapies became available for multiple sclerosis, the National MS Society organized the MS patients and they demanded that the payers cover the disease modifying therapies. That’s the kind of intense focus of advocacy that needs to be done for these noninvasive neuromodulation devices,” said Dr. Tepper.
The TEAM study was a double blind, randomized, sham-controlled trial of 538 patients who were asked to use neurostimulation for a 2-hour, continuous session within 4 hours of a moderate to severe migraine accompanied by at least one migraine-associated symptom. At 2 hours, 25.5% of those using the device achieved pain freedom, compared with 18.3% of those using the sham (P < .05). Among those using the device, 56.4% had freedom from most bothersome symptom, compared with 42.3% of those using the sham (P < .01).
Pain relief at 2 hours was more common in the device group (69.5% vs. 55.2%; P < .01), as was absence of all migraine-associated symptoms at 2 hours (42.5% vs. 34.1%; P < .05), sustained pain freedom at 24 hours (22.8% vs. 15.8%; P < .05), and sustained pain relief at 24 hours (45.9% vs. 34.4%; P < .01). There was no statistically significant between-group difference in use of rescue medications.
In the device group, 8.5% of patients experienced an adverse event, versus 2.9% in the sham group (P = .004). The only adverse reaction that occurred more frequently in the device group was forehead paresthesia, discomfort, and burning (3.5% vs. 0.4%; P = .009).
The study was funded by Cefaly. Dr. Tepper and Dr. Friedman have no relevant financial disclosures.
FROM AHS 2021
A large proportion of migraine patients are not offered preventive treatment
, new research suggests. Investigators found that among patients with migraine who are eligible for preventive therapy, more than a third were not offered this option. In addition, fewer than 10% were currently taking preventive medication, and an additional 10% had discontinued preventive therapy.
“We confirmed that as of 2012 to 2013 – the years these data were collected from a large, comprehensive survey – gaps in care remained,” said study investigator Stephanie J. Nahas, MD, director of the headache medicine fellowship program, Thomas Jefferson University, Philadelphia. “In this preventive-eligible population, 35% reported never even being offered preventive medication.”
Furthermore, only 28% of patients taking preventive medication experienced a reduction in headache frequency to less than 4 days per month, which is a primary goal of treatment, said Dr. Nahas. Disease burden, as measured with scales of disability and affective comorbidities, remained substantial.
The findings were presented at the American Headache Society’s 2021 annual meeting.
Lack of efficacy?
In 2019, the American Headache Society published a position statement recommending that preventive treatment be considered for patients who have migraine and four or more monthly headache days (MHDs), regardless of their level of associated disability. However, previous data suggest few patients who are eligible for preventive treatment receive it. In addition, many who have used preventive medications do not adhere to their regimens because of problems with tolerability, efficacy, or both.
To identify treatment gaps and characterize self-reported use of preventive medications for migraine, the investigators examined data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study, a web-based survey conducted in a representative U.S. sample from September 2012 through November 2013.
The survey identified and characterized patients who met modified criteria for migraine consistent with those in ICHD-3. The researchers classified respondents who had migraine and four or more MHDs as potentially eligible for migraine preventive treatment.
The investigators assessed the study population’s use of oral preventive medications, migraine-related disability and burden, willingness to take preventive treatment, and reasons for discontinuation.
Assessments included the Migraine Disability Assessment Questionnaire, the Patient Health Questionnaire–9 for depression, the Generalized Anxiety Disorder 7-Item Scale, the Migraine Specific Quality of Life questionnaire, and the Migraine Symptom Severity Scale.
In all, 16,789 respondents met criteria for migraine, and 6,579 (39.2%) reported having at least four MHDs. The median age of this subgroup that was eligible for preventive treatment was 40.3 years, and approximately 79% were women.
Only 9.8% of respondents who were eligible for preventive medications were currently using an oral preventive medication. Among those who had ever tried an oral preventive medication, 53.6% discontinued it. Efficacy for patients who used medications appeared to be inadequate. Among all current users of preventive treatment, 68.4% continued to have at least four MHDs.
The researchers assessed treatment eligibility among patients not taking preventive medication. Among respondents who had never used a preventive treatment, 35.7% were eligible to receive it. Among all users who had discontinued preventive medication, 61.0% were still eligible to receive it.
Attitudes toward injectables
Among respondents who had never used a preventive treatment, 64.3% had zero to three MHDs. The remaining 35.7% had 4-7, 8-14, or 15 or more MHDs. Among current users of preventive treatments, 68.4% had four or more MHDs. Among those who had discontinued preventive treatment, 61.0% had four or more MHDs.
Patients who have never used preventive medication “have substantial management gaps,” said Dr. Nahas. High proportions of these patients have moderate or severe disability (64.7%), depression (43%), and anxiety (39%). The rates of these outcomes are higher in users who discontinued treatment, likely because of confounding by indication, she added.
The prevalence of anxiety was similar between those who currently used, formerly used, or never used preventive medications. However, there were differences between never-users and current or former users with respect to moderate to severe depression (never-users, 43%; current users, 49.4%; discontinued users, 46.5%) and moderate to severe disability (never-users, 64.7%; current users, 80.4%; discontinued users, 78.9%).
In all, 44.6% of those who discontinued preventive therapy reported safety and tolerability problems as reasons for stopping treatment. In addition, 39.7% reported that these medications did not prevent enough headaches. Some patients reported partial or temporary efficacy as a reason for discontinuation. Other reasons were related to health care costs and access and personal preferences. Only 9.2% of patients who discontinued treatment said that their headaches improved enough to stop medication.
The investigators also analyzed respondents’ interest in preventive therapies. Among respondents who had never used preventive therapies, 61.8% of those who were eligible to use them were somewhat or very interested in trying an oral prescription medication for migraine prevention. However, 59.1% of never-users who were eligible for preventive medications were not at all interested, not sure, or needed more information about trying an injectable preventive medication. About 40% were not at all interested in injectables. In general, current users and those who had discontinued medication were more interested in preventive medication, including injectables.
‘Disheartening’ discontinuation rates
There are likely multiple reasons for the low rate of migraine prevention treatment, said Dr. Nahas. Many people with migraine never consult a clinician, owing to factors such as stigma, cost, lack of access, and lack of awareness. In addition, patients with migraine are frequently misdiagnosed, she added.
“Other data suggest that only about a quarter of people with episodic migraine and under 5% of people with chronic migraine consult a clinician, receive an accurate diagnosis, and are prescribed appropriate therapy,” said Dr. Nahas.
When the data in this analysis were gathered, public awareness of migraine was much lower than it is today, and injectable migraine therapies had not gained broad acceptance, she noted. Dr. Nahas added it is possible that attitudes toward injectable preventive medications have changed.
“Would people still prefer daily oral medications? We can’t know for sure until we start asking,” she said. In addition, scientific advances and educational outreach have increased clinicians’ awareness, interest, and skill regarding injectable medications, she said.
“I would certainly hope to see that a much greater proportion of preventive-eligible persons with migraine were at least offered, if not currently taking, preventive medication,” said Dr. Nahas. “But there’s no pleasing everyone, so I think we would still see somewhat disheartening discontinuation rates. The reasons for discontinuation, however, might be less typified by concerns about safety and tolerability.”
Still relevant
Commenting on the study, Mia Tova Minen, MD, chief of headache research and associate professor of neurology and population health at NYU Langone Health, New York, noted that although CaMEO is an older study, its results are still highly relevant.
“Unfortunately, primary care providers are still uncomfortable prescribing migraine preventive medications, and this accounts for the large percentage [of patients] with migraine who, while eligible for migraine preventive therapy, are not offered it,” she said.
Although the public and primary care physicians are now more aware of preventive treatments for migraine, “the number of people offered migraine preventive medication still needs to increase dramatically,” said Dr. Minen.
The American Academy of Neurology’s guidelines for migraine prevention were published in 2012 and are currently being updated. The updated guidelines may include new evidence for candesartan and emerging treatments, such as melatonin and aerobic exercise.
“It is my hope that primary care providers will become more comfortable prescribing migraine preventive medications sooner,” said Dr. Minen.
The current findings suggest a need for additional ways of educating patients with migraine who are eligible for preventive therapies so that they can advocate for themselves, she added. They also suggest the idea of demanding more insurance coverage of behavioral therapies for migraine, because data indicate that these treatments have long-term efficacy and good safety profiles, said Dr. Minen.
An ‘invisible’ disorder
Also commenting on the study, Barbara L. Nye, MD, director of the headache fellowship and codirector of the headache clinic at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said the CaMEO cohort likely is representative of the general population of patients with migraine.
She noted that a significant weakness of the current study is that it examined data collected before the Food and Drug Administration approved monoclonal antibodies and therefore does not reflect patients’ current experience with medications.
“I believe that the attitudes and fears surrounding the use of injectable medication are now likely far less than previously reported, given the positive track record the new generation of once-a-month injectable medications has,” said Dr. Nye.
The findings reinforce the idea that either patients are not talking to their primary care physicians about their headaches and disability or that clinicians are not asking about them, she added. “Both issues are likely linked to the stigma that this disease state has surrounding it. This is an invisible neurological disorder to most,” Dr. Nye said.
The study was sponsored by Allergan before it was acquired by AbbVie. Dr. Nahas has served as a consultant, advisory board member, or speaker for AbbVie/Allergan, Alder/Lundbeck, Amgen/Novartis, Biohaven, Eli Lilly, Impel, Nesos Corp, Supernus, Teva, Theranica, and Zosano. She has not received and will not receive monetary compensation for this research. Dr. Minen has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Investigators found that among patients with migraine who are eligible for preventive therapy, more than a third were not offered this option. In addition, fewer than 10% were currently taking preventive medication, and an additional 10% had discontinued preventive therapy.
“We confirmed that as of 2012 to 2013 – the years these data were collected from a large, comprehensive survey – gaps in care remained,” said study investigator Stephanie J. Nahas, MD, director of the headache medicine fellowship program, Thomas Jefferson University, Philadelphia. “In this preventive-eligible population, 35% reported never even being offered preventive medication.”
Furthermore, only 28% of patients taking preventive medication experienced a reduction in headache frequency to less than 4 days per month, which is a primary goal of treatment, said Dr. Nahas. Disease burden, as measured with scales of disability and affective comorbidities, remained substantial.
The findings were presented at the American Headache Society’s 2021 annual meeting.
Lack of efficacy?
In 2019, the American Headache Society published a position statement recommending that preventive treatment be considered for patients who have migraine and four or more monthly headache days (MHDs), regardless of their level of associated disability. However, previous data suggest few patients who are eligible for preventive treatment receive it. In addition, many who have used preventive medications do not adhere to their regimens because of problems with tolerability, efficacy, or both.
To identify treatment gaps and characterize self-reported use of preventive medications for migraine, the investigators examined data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study, a web-based survey conducted in a representative U.S. sample from September 2012 through November 2013.
The survey identified and characterized patients who met modified criteria for migraine consistent with those in ICHD-3. The researchers classified respondents who had migraine and four or more MHDs as potentially eligible for migraine preventive treatment.
The investigators assessed the study population’s use of oral preventive medications, migraine-related disability and burden, willingness to take preventive treatment, and reasons for discontinuation.
Assessments included the Migraine Disability Assessment Questionnaire, the Patient Health Questionnaire–9 for depression, the Generalized Anxiety Disorder 7-Item Scale, the Migraine Specific Quality of Life questionnaire, and the Migraine Symptom Severity Scale.
In all, 16,789 respondents met criteria for migraine, and 6,579 (39.2%) reported having at least four MHDs. The median age of this subgroup that was eligible for preventive treatment was 40.3 years, and approximately 79% were women.
Only 9.8% of respondents who were eligible for preventive medications were currently using an oral preventive medication. Among those who had ever tried an oral preventive medication, 53.6% discontinued it. Efficacy for patients who used medications appeared to be inadequate. Among all current users of preventive treatment, 68.4% continued to have at least four MHDs.
The researchers assessed treatment eligibility among patients not taking preventive medication. Among respondents who had never used a preventive treatment, 35.7% were eligible to receive it. Among all users who had discontinued preventive medication, 61.0% were still eligible to receive it.
Attitudes toward injectables
Among respondents who had never used a preventive treatment, 64.3% had zero to three MHDs. The remaining 35.7% had 4-7, 8-14, or 15 or more MHDs. Among current users of preventive treatments, 68.4% had four or more MHDs. Among those who had discontinued preventive treatment, 61.0% had four or more MHDs.
Patients who have never used preventive medication “have substantial management gaps,” said Dr. Nahas. High proportions of these patients have moderate or severe disability (64.7%), depression (43%), and anxiety (39%). The rates of these outcomes are higher in users who discontinued treatment, likely because of confounding by indication, she added.
The prevalence of anxiety was similar between those who currently used, formerly used, or never used preventive medications. However, there were differences between never-users and current or former users with respect to moderate to severe depression (never-users, 43%; current users, 49.4%; discontinued users, 46.5%) and moderate to severe disability (never-users, 64.7%; current users, 80.4%; discontinued users, 78.9%).
In all, 44.6% of those who discontinued preventive therapy reported safety and tolerability problems as reasons for stopping treatment. In addition, 39.7% reported that these medications did not prevent enough headaches. Some patients reported partial or temporary efficacy as a reason for discontinuation. Other reasons were related to health care costs and access and personal preferences. Only 9.2% of patients who discontinued treatment said that their headaches improved enough to stop medication.
The investigators also analyzed respondents’ interest in preventive therapies. Among respondents who had never used preventive therapies, 61.8% of those who were eligible to use them were somewhat or very interested in trying an oral prescription medication for migraine prevention. However, 59.1% of never-users who were eligible for preventive medications were not at all interested, not sure, or needed more information about trying an injectable preventive medication. About 40% were not at all interested in injectables. In general, current users and those who had discontinued medication were more interested in preventive medication, including injectables.
‘Disheartening’ discontinuation rates
There are likely multiple reasons for the low rate of migraine prevention treatment, said Dr. Nahas. Many people with migraine never consult a clinician, owing to factors such as stigma, cost, lack of access, and lack of awareness. In addition, patients with migraine are frequently misdiagnosed, she added.
“Other data suggest that only about a quarter of people with episodic migraine and under 5% of people with chronic migraine consult a clinician, receive an accurate diagnosis, and are prescribed appropriate therapy,” said Dr. Nahas.
When the data in this analysis were gathered, public awareness of migraine was much lower than it is today, and injectable migraine therapies had not gained broad acceptance, she noted. Dr. Nahas added it is possible that attitudes toward injectable preventive medications have changed.
“Would people still prefer daily oral medications? We can’t know for sure until we start asking,” she said. In addition, scientific advances and educational outreach have increased clinicians’ awareness, interest, and skill regarding injectable medications, she said.
“I would certainly hope to see that a much greater proportion of preventive-eligible persons with migraine were at least offered, if not currently taking, preventive medication,” said Dr. Nahas. “But there’s no pleasing everyone, so I think we would still see somewhat disheartening discontinuation rates. The reasons for discontinuation, however, might be less typified by concerns about safety and tolerability.”
Still relevant
Commenting on the study, Mia Tova Minen, MD, chief of headache research and associate professor of neurology and population health at NYU Langone Health, New York, noted that although CaMEO is an older study, its results are still highly relevant.
“Unfortunately, primary care providers are still uncomfortable prescribing migraine preventive medications, and this accounts for the large percentage [of patients] with migraine who, while eligible for migraine preventive therapy, are not offered it,” she said.
Although the public and primary care physicians are now more aware of preventive treatments for migraine, “the number of people offered migraine preventive medication still needs to increase dramatically,” said Dr. Minen.
The American Academy of Neurology’s guidelines for migraine prevention were published in 2012 and are currently being updated. The updated guidelines may include new evidence for candesartan and emerging treatments, such as melatonin and aerobic exercise.
“It is my hope that primary care providers will become more comfortable prescribing migraine preventive medications sooner,” said Dr. Minen.
The current findings suggest a need for additional ways of educating patients with migraine who are eligible for preventive therapies so that they can advocate for themselves, she added. They also suggest the idea of demanding more insurance coverage of behavioral therapies for migraine, because data indicate that these treatments have long-term efficacy and good safety profiles, said Dr. Minen.
An ‘invisible’ disorder
Also commenting on the study, Barbara L. Nye, MD, director of the headache fellowship and codirector of the headache clinic at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said the CaMEO cohort likely is representative of the general population of patients with migraine.
She noted that a significant weakness of the current study is that it examined data collected before the Food and Drug Administration approved monoclonal antibodies and therefore does not reflect patients’ current experience with medications.
“I believe that the attitudes and fears surrounding the use of injectable medication are now likely far less than previously reported, given the positive track record the new generation of once-a-month injectable medications has,” said Dr. Nye.
The findings reinforce the idea that either patients are not talking to their primary care physicians about their headaches and disability or that clinicians are not asking about them, she added. “Both issues are likely linked to the stigma that this disease state has surrounding it. This is an invisible neurological disorder to most,” Dr. Nye said.
The study was sponsored by Allergan before it was acquired by AbbVie. Dr. Nahas has served as a consultant, advisory board member, or speaker for AbbVie/Allergan, Alder/Lundbeck, Amgen/Novartis, Biohaven, Eli Lilly, Impel, Nesos Corp, Supernus, Teva, Theranica, and Zosano. She has not received and will not receive monetary compensation for this research. Dr. Minen has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Investigators found that among patients with migraine who are eligible for preventive therapy, more than a third were not offered this option. In addition, fewer than 10% were currently taking preventive medication, and an additional 10% had discontinued preventive therapy.
“We confirmed that as of 2012 to 2013 – the years these data were collected from a large, comprehensive survey – gaps in care remained,” said study investigator Stephanie J. Nahas, MD, director of the headache medicine fellowship program, Thomas Jefferson University, Philadelphia. “In this preventive-eligible population, 35% reported never even being offered preventive medication.”
Furthermore, only 28% of patients taking preventive medication experienced a reduction in headache frequency to less than 4 days per month, which is a primary goal of treatment, said Dr. Nahas. Disease burden, as measured with scales of disability and affective comorbidities, remained substantial.
The findings were presented at the American Headache Society’s 2021 annual meeting.
Lack of efficacy?
In 2019, the American Headache Society published a position statement recommending that preventive treatment be considered for patients who have migraine and four or more monthly headache days (MHDs), regardless of their level of associated disability. However, previous data suggest few patients who are eligible for preventive treatment receive it. In addition, many who have used preventive medications do not adhere to their regimens because of problems with tolerability, efficacy, or both.
To identify treatment gaps and characterize self-reported use of preventive medications for migraine, the investigators examined data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study, a web-based survey conducted in a representative U.S. sample from September 2012 through November 2013.
The survey identified and characterized patients who met modified criteria for migraine consistent with those in ICHD-3. The researchers classified respondents who had migraine and four or more MHDs as potentially eligible for migraine preventive treatment.
The investigators assessed the study population’s use of oral preventive medications, migraine-related disability and burden, willingness to take preventive treatment, and reasons for discontinuation.
Assessments included the Migraine Disability Assessment Questionnaire, the Patient Health Questionnaire–9 for depression, the Generalized Anxiety Disorder 7-Item Scale, the Migraine Specific Quality of Life questionnaire, and the Migraine Symptom Severity Scale.
In all, 16,789 respondents met criteria for migraine, and 6,579 (39.2%) reported having at least four MHDs. The median age of this subgroup that was eligible for preventive treatment was 40.3 years, and approximately 79% were women.
Only 9.8% of respondents who were eligible for preventive medications were currently using an oral preventive medication. Among those who had ever tried an oral preventive medication, 53.6% discontinued it. Efficacy for patients who used medications appeared to be inadequate. Among all current users of preventive treatment, 68.4% continued to have at least four MHDs.
The researchers assessed treatment eligibility among patients not taking preventive medication. Among respondents who had never used a preventive treatment, 35.7% were eligible to receive it. Among all users who had discontinued preventive medication, 61.0% were still eligible to receive it.
Attitudes toward injectables
Among respondents who had never used a preventive treatment, 64.3% had zero to three MHDs. The remaining 35.7% had 4-7, 8-14, or 15 or more MHDs. Among current users of preventive treatments, 68.4% had four or more MHDs. Among those who had discontinued preventive treatment, 61.0% had four or more MHDs.
Patients who have never used preventive medication “have substantial management gaps,” said Dr. Nahas. High proportions of these patients have moderate or severe disability (64.7%), depression (43%), and anxiety (39%). The rates of these outcomes are higher in users who discontinued treatment, likely because of confounding by indication, she added.
The prevalence of anxiety was similar between those who currently used, formerly used, or never used preventive medications. However, there were differences between never-users and current or former users with respect to moderate to severe depression (never-users, 43%; current users, 49.4%; discontinued users, 46.5%) and moderate to severe disability (never-users, 64.7%; current users, 80.4%; discontinued users, 78.9%).
In all, 44.6% of those who discontinued preventive therapy reported safety and tolerability problems as reasons for stopping treatment. In addition, 39.7% reported that these medications did not prevent enough headaches. Some patients reported partial or temporary efficacy as a reason for discontinuation. Other reasons were related to health care costs and access and personal preferences. Only 9.2% of patients who discontinued treatment said that their headaches improved enough to stop medication.
The investigators also analyzed respondents’ interest in preventive therapies. Among respondents who had never used preventive therapies, 61.8% of those who were eligible to use them were somewhat or very interested in trying an oral prescription medication for migraine prevention. However, 59.1% of never-users who were eligible for preventive medications were not at all interested, not sure, or needed more information about trying an injectable preventive medication. About 40% were not at all interested in injectables. In general, current users and those who had discontinued medication were more interested in preventive medication, including injectables.
‘Disheartening’ discontinuation rates
There are likely multiple reasons for the low rate of migraine prevention treatment, said Dr. Nahas. Many people with migraine never consult a clinician, owing to factors such as stigma, cost, lack of access, and lack of awareness. In addition, patients with migraine are frequently misdiagnosed, she added.
“Other data suggest that only about a quarter of people with episodic migraine and under 5% of people with chronic migraine consult a clinician, receive an accurate diagnosis, and are prescribed appropriate therapy,” said Dr. Nahas.
When the data in this analysis were gathered, public awareness of migraine was much lower than it is today, and injectable migraine therapies had not gained broad acceptance, she noted. Dr. Nahas added it is possible that attitudes toward injectable preventive medications have changed.
“Would people still prefer daily oral medications? We can’t know for sure until we start asking,” she said. In addition, scientific advances and educational outreach have increased clinicians’ awareness, interest, and skill regarding injectable medications, she said.
“I would certainly hope to see that a much greater proportion of preventive-eligible persons with migraine were at least offered, if not currently taking, preventive medication,” said Dr. Nahas. “But there’s no pleasing everyone, so I think we would still see somewhat disheartening discontinuation rates. The reasons for discontinuation, however, might be less typified by concerns about safety and tolerability.”
Still relevant
Commenting on the study, Mia Tova Minen, MD, chief of headache research and associate professor of neurology and population health at NYU Langone Health, New York, noted that although CaMEO is an older study, its results are still highly relevant.
“Unfortunately, primary care providers are still uncomfortable prescribing migraine preventive medications, and this accounts for the large percentage [of patients] with migraine who, while eligible for migraine preventive therapy, are not offered it,” she said.
Although the public and primary care physicians are now more aware of preventive treatments for migraine, “the number of people offered migraine preventive medication still needs to increase dramatically,” said Dr. Minen.
The American Academy of Neurology’s guidelines for migraine prevention were published in 2012 and are currently being updated. The updated guidelines may include new evidence for candesartan and emerging treatments, such as melatonin and aerobic exercise.
“It is my hope that primary care providers will become more comfortable prescribing migraine preventive medications sooner,” said Dr. Minen.
The current findings suggest a need for additional ways of educating patients with migraine who are eligible for preventive therapies so that they can advocate for themselves, she added. They also suggest the idea of demanding more insurance coverage of behavioral therapies for migraine, because data indicate that these treatments have long-term efficacy and good safety profiles, said Dr. Minen.
An ‘invisible’ disorder
Also commenting on the study, Barbara L. Nye, MD, director of the headache fellowship and codirector of the headache clinic at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said the CaMEO cohort likely is representative of the general population of patients with migraine.
She noted that a significant weakness of the current study is that it examined data collected before the Food and Drug Administration approved monoclonal antibodies and therefore does not reflect patients’ current experience with medications.
“I believe that the attitudes and fears surrounding the use of injectable medication are now likely far less than previously reported, given the positive track record the new generation of once-a-month injectable medications has,” said Dr. Nye.
The findings reinforce the idea that either patients are not talking to their primary care physicians about their headaches and disability or that clinicians are not asking about them, she added. “Both issues are likely linked to the stigma that this disease state has surrounding it. This is an invisible neurological disorder to most,” Dr. Nye said.
The study was sponsored by Allergan before it was acquired by AbbVie. Dr. Nahas has served as a consultant, advisory board member, or speaker for AbbVie/Allergan, Alder/Lundbeck, Amgen/Novartis, Biohaven, Eli Lilly, Impel, Nesos Corp, Supernus, Teva, Theranica, and Zosano. She has not received and will not receive monetary compensation for this research. Dr. Minen has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AHS 2021