TBD Meeting (3518-21)

OnabotulinumtoxinA alone provides relief from chronic migraine, and addition of anti-calcitonin gene-related peptide (CGRP) antibodies may boost the benefit, according to a large retrospective analysis. The results lend hope that the combination may be synergistic, according to Andrew Blumenfeld, MD, director of the Headache Center of Southern California in Carlsbad. Dr. Blumenfeld presented at the American Headache Society’s 2021 annual meeting. The study was published online April 21 in Pain Therapy.

The retrospective analysis showed a 4-day reduction in headache days per month. In contrast, in the pivotal study for erenumab, the most commonly used anti-CGRP antibody among subjects in the study, showed a 2-day benefit in a subanalysis of patients who had failed at least two oral preventives.

There is mechanistic evidence to suggest the two therapies could be synergistic. OnabotulinumtoxinA is believed to inhibit the release of CGRP, and antibodies reduce CGRP levels. OnabotulinumtoxinA prevents activation of C-fibers in the trigeminal sensory afferents, but does not affect A-delta fibers.

On the other hand, most data indicate that the anti-CGRP antibody fremanezumab prevents activation of A-delta but not C-fibers, and a recent review argues that CGRP antibody nonresponders may have migraines driven by C-fibers or other pathways. “Thus, concomitant use of medications blocking the activation of meningeal C-fibers may provide a synergistic effect on the trigeminal nociceptive pathway,” the authors wrote.
 

Study finding match clinical practice

The results of the new study strengthen the case that the combination is effective, though proof would require prospective, randomized trials. “I think that it really gives credibility to what we are seeing in practice, which is that combined therapy often is much better than therapy with onabotulinumtoxinA alone, said Deborah Friedman, MD, MPH, who was asked to comment on the findings. Dr. Friedman is professor of neurology and ophthalmology at the University of Texas, Dallas.

The extra 4 migraine-free days per month is a significant benefit, said Stewart Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “It’s an extra month and a half of no disability per year, and that’s on top of what onabotulinumtoxinA does. So it’s really a very important clinical finding,” Dr. Tepper said in an interview.

Improvements with combination therapy

The study was a chart review of 257 patients who started on onabotulinumtoxinA and later initiated anti-CGRP antibody therapy. A total of 104 completed four visits after initiation of anti-CGRP antibody therapy (completers). Before starting any therapy, patients reported an average of 21 headache days per month in the overall group, and 22 among completers. That frequency dropped to 12 in both groups after onabotulinumtoxinA therapy (overall group difference, –9 days; 95% confidence interval, –8 to –11 days; completers group difference, –10; 95% CI, –7 to –12 days).

A total of 77.8% of subjects in the overall cohort took erenumab, 16.3% took galcanezumab, and 5.8% took fremanezumab. In the completers cohort, the percentages were 84.5%, 10.7%, and 4.9%, respectively.

Compared with baseline, both completers and noncompleters had clinically significant improvements in disability, as measured by at least a 5-point improvement in Migraine Disability Assessment (MIDAS) score at the 3-month visit (–5.8 for completers and –6.3 for the overall cohort group), the 6-month visit (–6.6 and –11.1), the 9-month visit (–8.3 and –6.1), and 1 year (–12.7 and –8.4).

At the first visit, 33.0% of completers had at least a 5-point reduction in MIDAS, as did 36.0% of the overall cohort group, and the trend continued at 6 months (39.8% and 45.1%), 9 months (43.7% and 43.7%), and at 1 year (45.3% and 44.8%).

The study was funded by Allergan. Dr. Blumenfeld has served on advisory boards for Aeon, AbbVie, Amgen, Alder, Biohaven, Teva, Supernus, Promius, Eaglet, and Lilly, and has received funding for speaking from AbbVie, Amgen, Pernix, Supernus, Depomed, Avanir, Promius, Teva, Eli Lilly, Lundbeck, Novartis, and Theranica. Dr. Tepper has consulted for Teva. Dr. Friedman has been on the advisory board for Allergan, Amgen, Lundbeck, Eli Lilly, and Teva Pharmaceuticals, and has received grant support from Allergan and Eli Lilly.

OnabotulinumtoxinA alone provides relief from chronic migraine, and addition of anti-calcitonin gene-related peptide (CGRP) antibodies may boost the benefit, according to a large retrospective analysis. The results lend hope that the combination may be synergistic, according to Andrew Blumenfeld, MD, director of the Headache Center of Southern California in Carlsbad. Dr. Blumenfeld presented at the American Headache Society’s 2021 annual meeting. The study was published online April 21 in Pain Therapy.

The retrospective analysis showed a 4-day reduction in headache days per month. In contrast, in the pivotal study for erenumab, the most commonly used anti-CGRP antibody among subjects in the study, showed a 2-day benefit in a subanalysis of patients who had failed at least two oral preventives.

There is mechanistic evidence to suggest the two therapies could be synergistic. OnabotulinumtoxinA is believed to inhibit the release of CGRP, and antibodies reduce CGRP levels. OnabotulinumtoxinA prevents activation of C-fibers in the trigeminal sensory afferents, but does not affect A-delta fibers.

On the other hand, most data indicate that the anti-CGRP antibody fremanezumab prevents activation of A-delta but not C-fibers, and a recent review argues that CGRP antibody nonresponders may have migraines driven by C-fibers or other pathways. “Thus, concomitant use of medications blocking the activation of meningeal C-fibers may provide a synergistic effect on the trigeminal nociceptive pathway,” the authors wrote.
 

Study finding match clinical practice

The results of the new study strengthen the case that the combination is effective, though proof would require prospective, randomized trials. “I think that it really gives credibility to what we are seeing in practice, which is that combined therapy often is much better than therapy with onabotulinumtoxinA alone, said Deborah Friedman, MD, MPH, who was asked to comment on the findings. Dr. Friedman is professor of neurology and ophthalmology at the University of Texas, Dallas.

The extra 4 migraine-free days per month is a significant benefit, said Stewart Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “It’s an extra month and a half of no disability per year, and that’s on top of what onabotulinumtoxinA does. So it’s really a very important clinical finding,” Dr. Tepper said in an interview.

Improvements with combination therapy

The study was a chart review of 257 patients who started on onabotulinumtoxinA and later initiated anti-CGRP antibody therapy. A total of 104 completed four visits after initiation of anti-CGRP antibody therapy (completers). Before starting any therapy, patients reported an average of 21 headache days per month in the overall group, and 22 among completers. That frequency dropped to 12 in both groups after onabotulinumtoxinA therapy (overall group difference, –9 days; 95% confidence interval, –8 to –11 days; completers group difference, –10; 95% CI, –7 to –12 days).

A total of 77.8% of subjects in the overall cohort took erenumab, 16.3% took galcanezumab, and 5.8% took fremanezumab. In the completers cohort, the percentages were 84.5%, 10.7%, and 4.9%, respectively.

Compared with baseline, both completers and noncompleters had clinically significant improvements in disability, as measured by at least a 5-point improvement in Migraine Disability Assessment (MIDAS) score at the 3-month visit (–5.8 for completers and –6.3 for the overall cohort group), the 6-month visit (–6.6 and –11.1), the 9-month visit (–8.3 and –6.1), and 1 year (–12.7 and –8.4).

At the first visit, 33.0% of completers had at least a 5-point reduction in MIDAS, as did 36.0% of the overall cohort group, and the trend continued at 6 months (39.8% and 45.1%), 9 months (43.7% and 43.7%), and at 1 year (45.3% and 44.8%).

The study was funded by Allergan. Dr. Blumenfeld has served on advisory boards for Aeon, AbbVie, Amgen, Alder, Biohaven, Teva, Supernus, Promius, Eaglet, and Lilly, and has received funding for speaking from AbbVie, Amgen, Pernix, Supernus, Depomed, Avanir, Promius, Teva, Eli Lilly, Lundbeck, Novartis, and Theranica. Dr. Tepper has consulted for Teva. Dr. Friedman has been on the advisory board for Allergan, Amgen, Lundbeck, Eli Lilly, and Teva Pharmaceuticals, and has received grant support from Allergan and Eli Lilly.

OnabotulinumtoxinA alone provides relief from chronic migraine, and addition of anti-calcitonin gene-related peptide (CGRP) antibodies may boost the benefit, according to a large retrospective analysis. The results lend hope that the combination may be synergistic, according to Andrew Blumenfeld, MD, director of the Headache Center of Southern California in Carlsbad. Dr. Blumenfeld presented at the American Headache Society’s 2021 annual meeting. The study was published online April 21 in Pain Therapy.

The retrospective analysis showed a 4-day reduction in headache days per month. In contrast, in the pivotal study for erenumab, the most commonly used anti-CGRP antibody among subjects in the study, showed a 2-day benefit in a subanalysis of patients who had failed at least two oral preventives.

There is mechanistic evidence to suggest the two therapies could be synergistic. OnabotulinumtoxinA is believed to inhibit the release of CGRP, and antibodies reduce CGRP levels. OnabotulinumtoxinA prevents activation of C-fibers in the trigeminal sensory afferents, but does not affect A-delta fibers.

On the other hand, most data indicate that the anti-CGRP antibody fremanezumab prevents activation of A-delta but not C-fibers, and a recent review argues that CGRP antibody nonresponders may have migraines driven by C-fibers or other pathways. “Thus, concomitant use of medications blocking the activation of meningeal C-fibers may provide a synergistic effect on the trigeminal nociceptive pathway,” the authors wrote.
 

Study finding match clinical practice

The results of the new study strengthen the case that the combination is effective, though proof would require prospective, randomized trials. “I think that it really gives credibility to what we are seeing in practice, which is that combined therapy often is much better than therapy with onabotulinumtoxinA alone, said Deborah Friedman, MD, MPH, who was asked to comment on the findings. Dr. Friedman is professor of neurology and ophthalmology at the University of Texas, Dallas.

The extra 4 migraine-free days per month is a significant benefit, said Stewart Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “It’s an extra month and a half of no disability per year, and that’s on top of what onabotulinumtoxinA does. So it’s really a very important clinical finding,” Dr. Tepper said in an interview.

Improvements with combination therapy

The study was a chart review of 257 patients who started on onabotulinumtoxinA and later initiated anti-CGRP antibody therapy. A total of 104 completed four visits after initiation of anti-CGRP antibody therapy (completers). Before starting any therapy, patients reported an average of 21 headache days per month in the overall group, and 22 among completers. That frequency dropped to 12 in both groups after onabotulinumtoxinA therapy (overall group difference, –9 days; 95% confidence interval, –8 to –11 days; completers group difference, –10; 95% CI, –7 to –12 days).

A total of 77.8% of subjects in the overall cohort took erenumab, 16.3% took galcanezumab, and 5.8% took fremanezumab. In the completers cohort, the percentages were 84.5%, 10.7%, and 4.9%, respectively.

Compared with baseline, both completers and noncompleters had clinically significant improvements in disability, as measured by at least a 5-point improvement in Migraine Disability Assessment (MIDAS) score at the 3-month visit (–5.8 for completers and –6.3 for the overall cohort group), the 6-month visit (–6.6 and –11.1), the 9-month visit (–8.3 and –6.1), and 1 year (–12.7 and –8.4).

At the first visit, 33.0% of completers had at least a 5-point reduction in MIDAS, as did 36.0% of the overall cohort group, and the trend continued at 6 months (39.8% and 45.1%), 9 months (43.7% and 43.7%), and at 1 year (45.3% and 44.8%).

The study was funded by Allergan. Dr. Blumenfeld has served on advisory boards for Aeon, AbbVie, Amgen, Alder, Biohaven, Teva, Supernus, Promius, Eaglet, and Lilly, and has received funding for speaking from AbbVie, Amgen, Pernix, Supernus, Depomed, Avanir, Promius, Teva, Eli Lilly, Lundbeck, Novartis, and Theranica. Dr. Tepper has consulted for Teva. Dr. Friedman has been on the advisory board for Allergan, Amgen, Lundbeck, Eli Lilly, and Teva Pharmaceuticals, and has received grant support from Allergan and Eli Lilly.

Almost 50% of patients with migraine hesitate to seek appropriate care, new research shows. A survey of nearly 18,000 participants with migraine showed that 46% were reluctant to consult a physician about their condition. Among those who hesitated, 58% ultimately consulted a physician, but 42% did not.

Common reasons for failure to seek treatment included believing that migraine was not severe enough to warrant a consultation, worries about cost and health insurance, and concern that the health care professional would not take the disorder seriously.

This is the first study to query patients with migraine regarding whether and why they have hesitated to seek care, said coinvestigator Robert E. Shapiro, MD, PhD, professor of neurologic sciences and director of the division of headache medicine at the University of Vermont, Burlington. “Previous studies have noted differences in care seeking by demographic or other distinguishing characteristics but have not asked people with migraine whether they actually intended to seek or not seek such care,” he said.

Dr. Shapiro presented the findings at the American Headache Society’s 2021 annual meeting.
 

Delays prevent diagnosis and care

For patients with migraine, hesitating to consult a physician causes delays in, and sometimes prevents, receiving a diagnosis and appropriate care.

To assess the proportion of patients who hesitate to seek a consultation for migraine care, as well as reasons for doing so, the investigators examined data from the Observational Survey of the Epidemiology, Treatment, and Care of Migraine (OVERCOME) study. OVERCOME incorporated a prospective web-based survey that was administered to a representative sample of 41,925 individuals in the United States.

Eligible participants who completed the study’s baseline assessment had had at least one migraine attack in the previous year and either met criteria for migraine on the basis of a validated diagnostic screen or provided a self-report of a migraine diagnosis by a health care practitioner. In all, 39,494 participants reported whether they had hesitated to seek a consultation from a physician for migraine care. Of these, 17,951 were included in the analysis.

Among the 46% who hesitated to seek care, 58% ultimately sought migraine care, and 42% did not.

The investigators also examined sociodemographic characteristics and migraine-related data, including the number of monthly headache days and information regarding nausea, photophobia, and phonophobia.

Patient-reported outcomes included days with migraine-related disability during the past 3 months, treatment optimization, and the degree to which migraine limited regular activities. Investigators also examined participants’ health care use in the previous 12 months and reasons for hesitating to seek migraine care.
 

Reasons for hesitancy

A total of 17,920 participants provided reasons for hesitating to seek a migraine consultation. These included a desire to take care of migraine attacks on one’s own (45%), the belief that migraine would not be taken seriously (35%), the belief that the migraine attacks were not serious or painful enough (29%), inability to afford or unwillingness to spend money on care (29%), lack of or inadequate health insurance (21%), and fear of receiving a serious diagnosis (19%).

Reasons for hesitation differed between participants who ultimately sought a consultation with a physician and those who did not. Those who did not receive a consultation (n = 7,495) were more likely to want to take care of the migraine attacks on their own (48% vs. 43%) and to believe the attacks were not serious or painful enough (36% vs. 25%).

Participants who hesitated but later sought a consultation were more likely to report concerns that migraine would not be taken seriously (38% vs. 31%) and fear of receiving a serious diagnosis (22% vs. 15%).

Among those who did not seek a consultation versus those who did, a significantly higher proportion were women (76% vs. 73%; P < .001).

“This is an interesting finding, since prior studies have indicated that, overall, women with migraine are more likely to have consulted a doctor for it – and also more likely to have been diagnosed with it,” Dr. Shapiro said.

On the other hand, women were 30% more likely to visit emergency departments or urgent care clinics for migraine care than men, he noted.

“These findings suggest some women may be experiencing particular barriers to receiving successful consultation care and that they may persistently hesitate to seek it,” said Dr. Shapiro. He noted that these barriers might be financial or attitudinal.

“Women are reported to be less likely to receive treatment for pain conditions, and furthermore, stigma toward migraine in particular may limit its perceived seriousness,” he said.
 

‘Equitable access’ needed

Those with full-time employment were significantly more likely to seek a migraine consultation than were those who were not employed full time (46% vs. 42%; P < .001). Patients who sought care were more likely to have health insurance (87% vs. 78%; P < .001).

Having health insurance (odds ratio [OR], 1.99), having previously received a migraine diagnosis (OR, 2.71), and degree of disability (severe vs. none: OR, 2.76; moderate vs. none: OR, 2.04) were associated with increased likelihood of seeking a migraine consultation among those who initially hesitated. Other factors included being male (OR, 1.49), having nausea (OR, 1.15), or being employed full time (OR, 1.24).

“Taken together, our findings suggest consultation rates may be limited by financial barriers and pervasive attitudes that migraine is either not serious or is untreatable,” said Dr. Shapiro. Consistent with this hypothesis is the finding that individuals with migraine who had received an appropriate diagnosis and were therefore better informed about the condition were more likely to continue to seek care for it, he noted.

Because most outpatient medical encounters for migraine are with primary care practitioners, it may make sense to ensure that such clinicians are “well trained in diagnosing and treating common presentations of migraine,” Dr. Shapiro said. It is equally important to ensure “equitable access to health insurance to pay for these consultations,” he added.
 

‘Take migraine more seriously’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said the study was well designed.

Potential weaknesses include the fact that patients were required only to have one migraine attack per year and that not all were diagnosed by a headache specialist using ICHD-3 criteria.

Still, “online, validated, patient-reported data is quite acceptable,” said Dr. Rapoport, who was not involved in the research.

He noted that there is a clear message from the findings for all physicians who see patients with headache disorders: “You will increase the chance of patients consulting and continuing to consult when you make an accurate migraine diagnosis, take migraine more seriously, and understand the stigmas attached to it – and when there are reduced institutional barriers and costs of health care.”

The findings suggest that neurologists should strive to provide patients with ongoing care and medication, he added. In addition, there is a need for further education about the stigma associated with migraine and about how others view this disabling disease, Dr. Rapoport concluded.

The study was funded by Eli Lilly. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Rapoport has reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Almost 50% of patients with migraine hesitate to seek appropriate care, new research shows. A survey of nearly 18,000 participants with migraine showed that 46% were reluctant to consult a physician about their condition. Among those who hesitated, 58% ultimately consulted a physician, but 42% did not.

Common reasons for failure to seek treatment included believing that migraine was not severe enough to warrant a consultation, worries about cost and health insurance, and concern that the health care professional would not take the disorder seriously.

This is the first study to query patients with migraine regarding whether and why they have hesitated to seek care, said coinvestigator Robert E. Shapiro, MD, PhD, professor of neurologic sciences and director of the division of headache medicine at the University of Vermont, Burlington. “Previous studies have noted differences in care seeking by demographic or other distinguishing characteristics but have not asked people with migraine whether they actually intended to seek or not seek such care,” he said.

Dr. Shapiro presented the findings at the American Headache Society’s 2021 annual meeting.
 

Delays prevent diagnosis and care

For patients with migraine, hesitating to consult a physician causes delays in, and sometimes prevents, receiving a diagnosis and appropriate care.

To assess the proportion of patients who hesitate to seek a consultation for migraine care, as well as reasons for doing so, the investigators examined data from the Observational Survey of the Epidemiology, Treatment, and Care of Migraine (OVERCOME) study. OVERCOME incorporated a prospective web-based survey that was administered to a representative sample of 41,925 individuals in the United States.

Eligible participants who completed the study’s baseline assessment had had at least one migraine attack in the previous year and either met criteria for migraine on the basis of a validated diagnostic screen or provided a self-report of a migraine diagnosis by a health care practitioner. In all, 39,494 participants reported whether they had hesitated to seek a consultation from a physician for migraine care. Of these, 17,951 were included in the analysis.

Among the 46% who hesitated to seek care, 58% ultimately sought migraine care, and 42% did not.

The investigators also examined sociodemographic characteristics and migraine-related data, including the number of monthly headache days and information regarding nausea, photophobia, and phonophobia.

Patient-reported outcomes included days with migraine-related disability during the past 3 months, treatment optimization, and the degree to which migraine limited regular activities. Investigators also examined participants’ health care use in the previous 12 months and reasons for hesitating to seek migraine care.
 

Reasons for hesitancy

A total of 17,920 participants provided reasons for hesitating to seek a migraine consultation. These included a desire to take care of migraine attacks on one’s own (45%), the belief that migraine would not be taken seriously (35%), the belief that the migraine attacks were not serious or painful enough (29%), inability to afford or unwillingness to spend money on care (29%), lack of or inadequate health insurance (21%), and fear of receiving a serious diagnosis (19%).

Reasons for hesitation differed between participants who ultimately sought a consultation with a physician and those who did not. Those who did not receive a consultation (n = 7,495) were more likely to want to take care of the migraine attacks on their own (48% vs. 43%) and to believe the attacks were not serious or painful enough (36% vs. 25%).

Participants who hesitated but later sought a consultation were more likely to report concerns that migraine would not be taken seriously (38% vs. 31%) and fear of receiving a serious diagnosis (22% vs. 15%).

Among those who did not seek a consultation versus those who did, a significantly higher proportion were women (76% vs. 73%; P < .001).

“This is an interesting finding, since prior studies have indicated that, overall, women with migraine are more likely to have consulted a doctor for it – and also more likely to have been diagnosed with it,” Dr. Shapiro said.

On the other hand, women were 30% more likely to visit emergency departments or urgent care clinics for migraine care than men, he noted.

“These findings suggest some women may be experiencing particular barriers to receiving successful consultation care and that they may persistently hesitate to seek it,” said Dr. Shapiro. He noted that these barriers might be financial or attitudinal.

“Women are reported to be less likely to receive treatment for pain conditions, and furthermore, stigma toward migraine in particular may limit its perceived seriousness,” he said.
 

‘Equitable access’ needed

Those with full-time employment were significantly more likely to seek a migraine consultation than were those who were not employed full time (46% vs. 42%; P < .001). Patients who sought care were more likely to have health insurance (87% vs. 78%; P < .001).

Having health insurance (odds ratio [OR], 1.99), having previously received a migraine diagnosis (OR, 2.71), and degree of disability (severe vs. none: OR, 2.76; moderate vs. none: OR, 2.04) were associated with increased likelihood of seeking a migraine consultation among those who initially hesitated. Other factors included being male (OR, 1.49), having nausea (OR, 1.15), or being employed full time (OR, 1.24).

“Taken together, our findings suggest consultation rates may be limited by financial barriers and pervasive attitudes that migraine is either not serious or is untreatable,” said Dr. Shapiro. Consistent with this hypothesis is the finding that individuals with migraine who had received an appropriate diagnosis and were therefore better informed about the condition were more likely to continue to seek care for it, he noted.

Because most outpatient medical encounters for migraine are with primary care practitioners, it may make sense to ensure that such clinicians are “well trained in diagnosing and treating common presentations of migraine,” Dr. Shapiro said. It is equally important to ensure “equitable access to health insurance to pay for these consultations,” he added.
 

‘Take migraine more seriously’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said the study was well designed.

Potential weaknesses include the fact that patients were required only to have one migraine attack per year and that not all were diagnosed by a headache specialist using ICHD-3 criteria.

Still, “online, validated, patient-reported data is quite acceptable,” said Dr. Rapoport, who was not involved in the research.

He noted that there is a clear message from the findings for all physicians who see patients with headache disorders: “You will increase the chance of patients consulting and continuing to consult when you make an accurate migraine diagnosis, take migraine more seriously, and understand the stigmas attached to it – and when there are reduced institutional barriers and costs of health care.”

The findings suggest that neurologists should strive to provide patients with ongoing care and medication, he added. In addition, there is a need for further education about the stigma associated with migraine and about how others view this disabling disease, Dr. Rapoport concluded.

The study was funded by Eli Lilly. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Rapoport has reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Almost 50% of patients with migraine hesitate to seek appropriate care, new research shows. A survey of nearly 18,000 participants with migraine showed that 46% were reluctant to consult a physician about their condition. Among those who hesitated, 58% ultimately consulted a physician, but 42% did not.

Common reasons for failure to seek treatment included believing that migraine was not severe enough to warrant a consultation, worries about cost and health insurance, and concern that the health care professional would not take the disorder seriously.

This is the first study to query patients with migraine regarding whether and why they have hesitated to seek care, said coinvestigator Robert E. Shapiro, MD, PhD, professor of neurologic sciences and director of the division of headache medicine at the University of Vermont, Burlington. “Previous studies have noted differences in care seeking by demographic or other distinguishing characteristics but have not asked people with migraine whether they actually intended to seek or not seek such care,” he said.

Dr. Shapiro presented the findings at the American Headache Society’s 2021 annual meeting.
 

Delays prevent diagnosis and care

For patients with migraine, hesitating to consult a physician causes delays in, and sometimes prevents, receiving a diagnosis and appropriate care.

To assess the proportion of patients who hesitate to seek a consultation for migraine care, as well as reasons for doing so, the investigators examined data from the Observational Survey of the Epidemiology, Treatment, and Care of Migraine (OVERCOME) study. OVERCOME incorporated a prospective web-based survey that was administered to a representative sample of 41,925 individuals in the United States.

Eligible participants who completed the study’s baseline assessment had had at least one migraine attack in the previous year and either met criteria for migraine on the basis of a validated diagnostic screen or provided a self-report of a migraine diagnosis by a health care practitioner. In all, 39,494 participants reported whether they had hesitated to seek a consultation from a physician for migraine care. Of these, 17,951 were included in the analysis.

Among the 46% who hesitated to seek care, 58% ultimately sought migraine care, and 42% did not.

The investigators also examined sociodemographic characteristics and migraine-related data, including the number of monthly headache days and information regarding nausea, photophobia, and phonophobia.

Patient-reported outcomes included days with migraine-related disability during the past 3 months, treatment optimization, and the degree to which migraine limited regular activities. Investigators also examined participants’ health care use in the previous 12 months and reasons for hesitating to seek migraine care.
 

Reasons for hesitancy

A total of 17,920 participants provided reasons for hesitating to seek a migraine consultation. These included a desire to take care of migraine attacks on one’s own (45%), the belief that migraine would not be taken seriously (35%), the belief that the migraine attacks were not serious or painful enough (29%), inability to afford or unwillingness to spend money on care (29%), lack of or inadequate health insurance (21%), and fear of receiving a serious diagnosis (19%).

Reasons for hesitation differed between participants who ultimately sought a consultation with a physician and those who did not. Those who did not receive a consultation (n = 7,495) were more likely to want to take care of the migraine attacks on their own (48% vs. 43%) and to believe the attacks were not serious or painful enough (36% vs. 25%).

Participants who hesitated but later sought a consultation were more likely to report concerns that migraine would not be taken seriously (38% vs. 31%) and fear of receiving a serious diagnosis (22% vs. 15%).

Among those who did not seek a consultation versus those who did, a significantly higher proportion were women (76% vs. 73%; P < .001).

“This is an interesting finding, since prior studies have indicated that, overall, women with migraine are more likely to have consulted a doctor for it – and also more likely to have been diagnosed with it,” Dr. Shapiro said.

On the other hand, women were 30% more likely to visit emergency departments or urgent care clinics for migraine care than men, he noted.

“These findings suggest some women may be experiencing particular barriers to receiving successful consultation care and that they may persistently hesitate to seek it,” said Dr. Shapiro. He noted that these barriers might be financial or attitudinal.

“Women are reported to be less likely to receive treatment for pain conditions, and furthermore, stigma toward migraine in particular may limit its perceived seriousness,” he said.
 

‘Equitable access’ needed

Those with full-time employment were significantly more likely to seek a migraine consultation than were those who were not employed full time (46% vs. 42%; P < .001). Patients who sought care were more likely to have health insurance (87% vs. 78%; P < .001).

Having health insurance (odds ratio [OR], 1.99), having previously received a migraine diagnosis (OR, 2.71), and degree of disability (severe vs. none: OR, 2.76; moderate vs. none: OR, 2.04) were associated with increased likelihood of seeking a migraine consultation among those who initially hesitated. Other factors included being male (OR, 1.49), having nausea (OR, 1.15), or being employed full time (OR, 1.24).

“Taken together, our findings suggest consultation rates may be limited by financial barriers and pervasive attitudes that migraine is either not serious or is untreatable,” said Dr. Shapiro. Consistent with this hypothesis is the finding that individuals with migraine who had received an appropriate diagnosis and were therefore better informed about the condition were more likely to continue to seek care for it, he noted.

Because most outpatient medical encounters for migraine are with primary care practitioners, it may make sense to ensure that such clinicians are “well trained in diagnosing and treating common presentations of migraine,” Dr. Shapiro said. It is equally important to ensure “equitable access to health insurance to pay for these consultations,” he added.
 

‘Take migraine more seriously’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said the study was well designed.

Potential weaknesses include the fact that patients were required only to have one migraine attack per year and that not all were diagnosed by a headache specialist using ICHD-3 criteria.

Still, “online, validated, patient-reported data is quite acceptable,” said Dr. Rapoport, who was not involved in the research.

He noted that there is a clear message from the findings for all physicians who see patients with headache disorders: “You will increase the chance of patients consulting and continuing to consult when you make an accurate migraine diagnosis, take migraine more seriously, and understand the stigmas attached to it – and when there are reduced institutional barriers and costs of health care.”

The findings suggest that neurologists should strive to provide patients with ongoing care and medication, he added. In addition, there is a need for further education about the stigma associated with migraine and about how others view this disabling disease, Dr. Rapoport concluded.

The study was funded by Eli Lilly. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Rapoport has reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Patients overwhelmingly found telemedicine care for headache a satisfactory and beneficial experience during the COVID-19 pandemic, according to a study presented at the American Headache Society’s 2021 annual meeting. Most patients who used telemedicine said they would like to continue using it after the pandemic, though the study also revealed barriers to care for a small percentage of respondents.

“Telemedicine minimizes the physical and geographic barriers to health care, preserves personal protective equipment, and prevents the spread of COVID-19 by allowing encounters to happen in a socially distanced way,” said Chia-Chun Chiang, MD, assistant professor of neurology at Mayo Clinic in Rochester, Minn. “Telemedicine provides patients with opportunities to gain better control of their headache disorders while not having to commit to the time to travel and risk of exposure to COVID-19.” If insurance coverage for virtual care were rolled back, “patients and multiple levels of health care providers would be significantly affected,” she said.

The research relied on findings from a 15-question survey distributed by the nonprofit American Migraine Foundation through email and social media to more than 100,000 people. Among the 1,172 patients who responded to the survey, 1,098 had complete responses, and 86.6% were female.

The vast majority of these patients (93.8%) had had a previous diagnosis of a headache. Just over half (57.5%) said they used telemedicine during the study period, with most of those visits (85.5%) being follow-up care and 14.5% involving a new patient visit.

Among those who did not use telemedicine, most (56.1%) said they didn’t need a visit. However, a quarter of these respondents (25.2%) said they didn’t know telemedicine was an option, and 12.9% said they would have preferred telemedicine but it wasn’t offered by their doctors. A smaller proportion (3.5%) said they wanted to use virtual care but that their insurance did not cover it, and nearly as many (2.2%) said they wanted telemedicine but didn’t have the technology needed to use it.

“The COVID-19 pandemic has highlighted that reliable Internet service has contributed to disparities in access in many ways, including health care via telemedicine,” Dr. Chiang said. “Those who are not able to afford Internet, lack proficiency in the use of technology, or have cognitive impairment might not be able to utilize telemedicine.”

Among those who did receive telemedicine care for headache, about a third (34.4%) received care from a general neurologist while 43.7% saw a headache specialist and nearly a third (30.7%) saw a primary care provider. The remaining visits included 11.3% who saw headache nurse practitioners and 3.2% who saw headache nurses.

Most patients did not have a new or changed diagnosis at their visit; only 7.4% received a new headache diagnosis during their telemedicine appointment. Though 43.7% had no change to their therapy, a little more than half of patients (52.4%) received a new treatment, a finding that caught the interest of Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and past president of the International Headache Society.

“The techniques used [in virtual visits] were good enough for the caregiver to make critical decisions about how the patient was doing and what new treatment might be better for them,” said Dr. Rapoport, who was not involved in the research. “I believe that most headache specialists will gradually resume in office visits,” he said, but “this study shows it would be okay for some or most of the revisits to continue to be done virtually.”

The vast majority of patients rated their care as “very good” (62.1%) or “good” (20.7%). Less satisfied responses included 10.5% who felt their experience was “fair,” 3.6% who said it was “poor,” and 3.1% who gave other responses.

These results fit with the experience of Dr. Rapoport and of Paul B. Rizzoli, MD, associate professor of neurology at Harvard Medical School and clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital, both in Boston.

“Telemedicine worked better than we anticipated,” said Dr. Rizzoli when asked for comment. “I was especially surprised how comfortable I became with its use for many, but not all, new patients. While I don’t expect it to replace in-person visits, I do expect that it will and should be a permanent part of our care going forward, especially for follow-up visits.”

The findings supported that expectation as well: An overwhelming majority of those who responded to the survey (89.8%) also said they would like to keep receiving telemedicine care for their headache care and treatment. This percentage was split evenly between those who said they would like to always receive care virtually and those who would only want to use it for some appointments. A smaller proportion said they did not want to keep using virtual care (7.1%) or weren’t sure (3.1%).

“Telemedicine has become an essential tool for patients and a wide variety of clinicians,” Dr. Chiang reported during her presentation. “Telemedicine facilitated headache care for many patients during the COVID-19 pandemic, resulting in high patient satisfaction rates and a desire to continue to utilize telemedicine for future headache care for those who responded to the online survey.”

Dr. Rapoport noted that a particular benefit of telemedicine in his practice is avoiding transportation issues.

“In Santa Monica and Los Angeles, my patients coming from 10 or more miles away usually have to contend with difficult traffic, which created stress and often made them late and upset the office schedule,” Dr. Rapoport said. “I found that virtual visits were almost always shorter, on time, and were as effective for the patient as an in-person visit.”

Dr. Chiang drew attention, however, to the barriers to care found in the study, including not having or knowing of telemedicine as an option, and not having access to the technology or insurance coverage needed to take advantage of it. She listed three ways to address those challenges and increase health care accessibility to patients:
 

• Expand insurance coverage to reimburse telemedicine even after the pandemic.
• Widely promote and broadcast the use of virtual care.
• Make Internet access a priority as a necessity in society and expand access.

Dr. Rizzoli also noted some ways to improve telemedicine. “We could easily develop improved means of delivering vital signs and other bio-information over telemedicine to improve decision-making,” he said. “A difficult task going forward will be to fix legal questions associated with virtual visits across state lines which, especially in the small New England states, come up frequently and are currently illegal.”

Dr. Rapoport noted ways that patients can facilitate effective telemedicine visits. “Doctors should insist that patients keep careful records of their headaches, triggers, medicines, etc., either on paper or preferably via an app on their smartphones, which is usually always accessible,” Dr. Rapoport said. “With good data and a good electronic connection, the visit should go well.”

Among the study’s limitations were a comparatively small response rate (1.11% of those invited to participate) and ascertainment bias.

“The take-home message from the experience is that this turns out to be an effective, efficient and accepted means of delivering care that should be developed further,” Dr. Rizzoli said.

No external funding was noted. Dr. Chiang and Dr. Rizzoli had no disclosures. Dr. Rapoport has advised AbbVie, Amgen, Biohaven, Cala Health, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc and Zosano, and is on the speakers bureau of AbbVie, Amgen, Biohaven, Lundbeck and Teva Pharmaceutical Industries.

Patients overwhelmingly found telemedicine care for headache a satisfactory and beneficial experience during the COVID-19 pandemic, according to a study presented at the American Headache Society’s 2021 annual meeting. Most patients who used telemedicine said they would like to continue using it after the pandemic, though the study also revealed barriers to care for a small percentage of respondents.

“Telemedicine minimizes the physical and geographic barriers to health care, preserves personal protective equipment, and prevents the spread of COVID-19 by allowing encounters to happen in a socially distanced way,” said Chia-Chun Chiang, MD, assistant professor of neurology at Mayo Clinic in Rochester, Minn. “Telemedicine provides patients with opportunities to gain better control of their headache disorders while not having to commit to the time to travel and risk of exposure to COVID-19.” If insurance coverage for virtual care were rolled back, “patients and multiple levels of health care providers would be significantly affected,” she said.

The research relied on findings from a 15-question survey distributed by the nonprofit American Migraine Foundation through email and social media to more than 100,000 people. Among the 1,172 patients who responded to the survey, 1,098 had complete responses, and 86.6% were female.

The vast majority of these patients (93.8%) had had a previous diagnosis of a headache. Just over half (57.5%) said they used telemedicine during the study period, with most of those visits (85.5%) being follow-up care and 14.5% involving a new patient visit.

Among those who did not use telemedicine, most (56.1%) said they didn’t need a visit. However, a quarter of these respondents (25.2%) said they didn’t know telemedicine was an option, and 12.9% said they would have preferred telemedicine but it wasn’t offered by their doctors. A smaller proportion (3.5%) said they wanted to use virtual care but that their insurance did not cover it, and nearly as many (2.2%) said they wanted telemedicine but didn’t have the technology needed to use it.

“The COVID-19 pandemic has highlighted that reliable Internet service has contributed to disparities in access in many ways, including health care via telemedicine,” Dr. Chiang said. “Those who are not able to afford Internet, lack proficiency in the use of technology, or have cognitive impairment might not be able to utilize telemedicine.”

Among those who did receive telemedicine care for headache, about a third (34.4%) received care from a general neurologist while 43.7% saw a headache specialist and nearly a third (30.7%) saw a primary care provider. The remaining visits included 11.3% who saw headache nurse practitioners and 3.2% who saw headache nurses.

Most patients did not have a new or changed diagnosis at their visit; only 7.4% received a new headache diagnosis during their telemedicine appointment. Though 43.7% had no change to their therapy, a little more than half of patients (52.4%) received a new treatment, a finding that caught the interest of Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and past president of the International Headache Society.

“The techniques used [in virtual visits] were good enough for the caregiver to make critical decisions about how the patient was doing and what new treatment might be better for them,” said Dr. Rapoport, who was not involved in the research. “I believe that most headache specialists will gradually resume in office visits,” he said, but “this study shows it would be okay for some or most of the revisits to continue to be done virtually.”

The vast majority of patients rated their care as “very good” (62.1%) or “good” (20.7%). Less satisfied responses included 10.5% who felt their experience was “fair,” 3.6% who said it was “poor,” and 3.1% who gave other responses.

These results fit with the experience of Dr. Rapoport and of Paul B. Rizzoli, MD, associate professor of neurology at Harvard Medical School and clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital, both in Boston.

“Telemedicine worked better than we anticipated,” said Dr. Rizzoli when asked for comment. “I was especially surprised how comfortable I became with its use for many, but not all, new patients. While I don’t expect it to replace in-person visits, I do expect that it will and should be a permanent part of our care going forward, especially for follow-up visits.”

The findings supported that expectation as well: An overwhelming majority of those who responded to the survey (89.8%) also said they would like to keep receiving telemedicine care for their headache care and treatment. This percentage was split evenly between those who said they would like to always receive care virtually and those who would only want to use it for some appointments. A smaller proportion said they did not want to keep using virtual care (7.1%) or weren’t sure (3.1%).

“Telemedicine has become an essential tool for patients and a wide variety of clinicians,” Dr. Chiang reported during her presentation. “Telemedicine facilitated headache care for many patients during the COVID-19 pandemic, resulting in high patient satisfaction rates and a desire to continue to utilize telemedicine for future headache care for those who responded to the online survey.”

Dr. Rapoport noted that a particular benefit of telemedicine in his practice is avoiding transportation issues.

“In Santa Monica and Los Angeles, my patients coming from 10 or more miles away usually have to contend with difficult traffic, which created stress and often made them late and upset the office schedule,” Dr. Rapoport said. “I found that virtual visits were almost always shorter, on time, and were as effective for the patient as an in-person visit.”

Dr. Chiang drew attention, however, to the barriers to care found in the study, including not having or knowing of telemedicine as an option, and not having access to the technology or insurance coverage needed to take advantage of it. She listed three ways to address those challenges and increase health care accessibility to patients:
 

• Expand insurance coverage to reimburse telemedicine even after the pandemic.
• Widely promote and broadcast the use of virtual care.
• Make Internet access a priority as a necessity in society and expand access.

Dr. Rizzoli also noted some ways to improve telemedicine. “We could easily develop improved means of delivering vital signs and other bio-information over telemedicine to improve decision-making,” he said. “A difficult task going forward will be to fix legal questions associated with virtual visits across state lines which, especially in the small New England states, come up frequently and are currently illegal.”

Dr. Rapoport noted ways that patients can facilitate effective telemedicine visits. “Doctors should insist that patients keep careful records of their headaches, triggers, medicines, etc., either on paper or preferably via an app on their smartphones, which is usually always accessible,” Dr. Rapoport said. “With good data and a good electronic connection, the visit should go well.”

Among the study’s limitations were a comparatively small response rate (1.11% of those invited to participate) and ascertainment bias.

“The take-home message from the experience is that this turns out to be an effective, efficient and accepted means of delivering care that should be developed further,” Dr. Rizzoli said.

No external funding was noted. Dr. Chiang and Dr. Rizzoli had no disclosures. Dr. Rapoport has advised AbbVie, Amgen, Biohaven, Cala Health, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc and Zosano, and is on the speakers bureau of AbbVie, Amgen, Biohaven, Lundbeck and Teva Pharmaceutical Industries.

Patients overwhelmingly found telemedicine care for headache a satisfactory and beneficial experience during the COVID-19 pandemic, according to a study presented at the American Headache Society’s 2021 annual meeting. Most patients who used telemedicine said they would like to continue using it after the pandemic, though the study also revealed barriers to care for a small percentage of respondents.

“Telemedicine minimizes the physical and geographic barriers to health care, preserves personal protective equipment, and prevents the spread of COVID-19 by allowing encounters to happen in a socially distanced way,” said Chia-Chun Chiang, MD, assistant professor of neurology at Mayo Clinic in Rochester, Minn. “Telemedicine provides patients with opportunities to gain better control of their headache disorders while not having to commit to the time to travel and risk of exposure to COVID-19.” If insurance coverage for virtual care were rolled back, “patients and multiple levels of health care providers would be significantly affected,” she said.

The research relied on findings from a 15-question survey distributed by the nonprofit American Migraine Foundation through email and social media to more than 100,000 people. Among the 1,172 patients who responded to the survey, 1,098 had complete responses, and 86.6% were female.

The vast majority of these patients (93.8%) had had a previous diagnosis of a headache. Just over half (57.5%) said they used telemedicine during the study period, with most of those visits (85.5%) being follow-up care and 14.5% involving a new patient visit.

Among those who did not use telemedicine, most (56.1%) said they didn’t need a visit. However, a quarter of these respondents (25.2%) said they didn’t know telemedicine was an option, and 12.9% said they would have preferred telemedicine but it wasn’t offered by their doctors. A smaller proportion (3.5%) said they wanted to use virtual care but that their insurance did not cover it, and nearly as many (2.2%) said they wanted telemedicine but didn’t have the technology needed to use it.

“The COVID-19 pandemic has highlighted that reliable Internet service has contributed to disparities in access in many ways, including health care via telemedicine,” Dr. Chiang said. “Those who are not able to afford Internet, lack proficiency in the use of technology, or have cognitive impairment might not be able to utilize telemedicine.”

Among those who did receive telemedicine care for headache, about a third (34.4%) received care from a general neurologist while 43.7% saw a headache specialist and nearly a third (30.7%) saw a primary care provider. The remaining visits included 11.3% who saw headache nurse practitioners and 3.2% who saw headache nurses.

Most patients did not have a new or changed diagnosis at their visit; only 7.4% received a new headache diagnosis during their telemedicine appointment. Though 43.7% had no change to their therapy, a little more than half of patients (52.4%) received a new treatment, a finding that caught the interest of Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and past president of the International Headache Society.

“The techniques used [in virtual visits] were good enough for the caregiver to make critical decisions about how the patient was doing and what new treatment might be better for them,” said Dr. Rapoport, who was not involved in the research. “I believe that most headache specialists will gradually resume in office visits,” he said, but “this study shows it would be okay for some or most of the revisits to continue to be done virtually.”

The vast majority of patients rated their care as “very good” (62.1%) or “good” (20.7%). Less satisfied responses included 10.5% who felt their experience was “fair,” 3.6% who said it was “poor,” and 3.1% who gave other responses.

These results fit with the experience of Dr. Rapoport and of Paul B. Rizzoli, MD, associate professor of neurology at Harvard Medical School and clinical director of the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital, both in Boston.

“Telemedicine worked better than we anticipated,” said Dr. Rizzoli when asked for comment. “I was especially surprised how comfortable I became with its use for many, but not all, new patients. While I don’t expect it to replace in-person visits, I do expect that it will and should be a permanent part of our care going forward, especially for follow-up visits.”

The findings supported that expectation as well: An overwhelming majority of those who responded to the survey (89.8%) also said they would like to keep receiving telemedicine care for their headache care and treatment. This percentage was split evenly between those who said they would like to always receive care virtually and those who would only want to use it for some appointments. A smaller proportion said they did not want to keep using virtual care (7.1%) or weren’t sure (3.1%).

“Telemedicine has become an essential tool for patients and a wide variety of clinicians,” Dr. Chiang reported during her presentation. “Telemedicine facilitated headache care for many patients during the COVID-19 pandemic, resulting in high patient satisfaction rates and a desire to continue to utilize telemedicine for future headache care for those who responded to the online survey.”

Dr. Rapoport noted that a particular benefit of telemedicine in his practice is avoiding transportation issues.

“In Santa Monica and Los Angeles, my patients coming from 10 or more miles away usually have to contend with difficult traffic, which created stress and often made them late and upset the office schedule,” Dr. Rapoport said. “I found that virtual visits were almost always shorter, on time, and were as effective for the patient as an in-person visit.”

Dr. Chiang drew attention, however, to the barriers to care found in the study, including not having or knowing of telemedicine as an option, and not having access to the technology or insurance coverage needed to take advantage of it. She listed three ways to address those challenges and increase health care accessibility to patients:
 

• Expand insurance coverage to reimburse telemedicine even after the pandemic.
• Widely promote and broadcast the use of virtual care.
• Make Internet access a priority as a necessity in society and expand access.

Dr. Rizzoli also noted some ways to improve telemedicine. “We could easily develop improved means of delivering vital signs and other bio-information over telemedicine to improve decision-making,” he said. “A difficult task going forward will be to fix legal questions associated with virtual visits across state lines which, especially in the small New England states, come up frequently and are currently illegal.”

Dr. Rapoport noted ways that patients can facilitate effective telemedicine visits. “Doctors should insist that patients keep careful records of their headaches, triggers, medicines, etc., either on paper or preferably via an app on their smartphones, which is usually always accessible,” Dr. Rapoport said. “With good data and a good electronic connection, the visit should go well.”

Among the study’s limitations were a comparatively small response rate (1.11% of those invited to participate) and ascertainment bias.

“The take-home message from the experience is that this turns out to be an effective, efficient and accepted means of delivering care that should be developed further,” Dr. Rizzoli said.

No external funding was noted. Dr. Chiang and Dr. Rizzoli had no disclosures. Dr. Rapoport has advised AbbVie, Amgen, Biohaven, Cala Health, Satsuma, Teva Pharmaceutical Industries, Theranica, Xoc and Zosano, and is on the speakers bureau of AbbVie, Amgen, Biohaven, Lundbeck and Teva Pharmaceutical Industries.

A phase 2 study of the anti-calcitonin gene–related peptide (CGRP) antibody fremanezumab found no benefit of treatment in persistent posttraumatic headache. Anti-CGRP therapy had been predicted to be effective, given its history of improving other forms of headache, and preclinical studies had suggested that CGRP plays a role in late pain sensitization that can occur after mild brain injuries.

“There was a decrease in migraine headache days of moderate or severe intensity in both groups. But the difference between fremanezumab and placebo treatment was not statistically significant, either looking at that on a monthly basis or over the total 12 weeks of treatment,” Egilius L.H. Spierings, MD, PhD, said during his presentation of the results at the American Headache Society’s 2021 annual meeting. Dr. Spierings is medical director of the Boston Headache Institute.
 

Disappointing findings

“That’s sad. It’s just dreadful news,” Stewart J. Tepper, MD, professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. Dr. Tepper was not involved in the study. The results suggest that CGRP mechanisms may not be relevant to persistent posttraumatic headache, but it could still play a role at onset. “We have to rethink this. Either it’s that chronic, persistent posttraumatic headache does not have a CGRP biology, or it’s that you have to get to them earlier [in the disease process],” he said.

The negative results were surprising, according to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and former president of the International Headache Society. He noted that the study was small, and the researchers were unable to conduct subgroup analyses. “Posttraumatic headaches are usually broken down into those that phenotypically look like migraine, or phenotypically look like tension-type headache. It would have been nice to know if most of them had what clinically appears to be tension-type headache, and maybe that’s why they didn’t respond. Or did most of them have a migraine phenotype, and then it would be a little more surprising that they didn’t respond,” Dr. Rapoport said in an interview.

As a result, he believes that further studies might show that fremanezumab is an effective treatment for posttraumatic headache. “I would not give up on it. I expect that a larger study with better power, and a better idea of exactly what was wrong with the patients, might end up being a positive study,” he said.

Although most posttraumatic headaches resolve within weeks or months, some can linger or become chronic for years. Pain medication is often prescribed but should not be, according to Dr. Rapoport, because it can lead to medication overuse headache that worsens the problem. “So we badly need a good temporary preventive treatment. The thought of giving our newest, most effective preventive medications, with few adverse events, is a good one. It just didn’t seem to work in this fairly small and underpowered study,” he said.
 

The phase 2 trial

The trial included 87 patients with new-onset or significant worsening of headache following a minor traumatic brain injury or concussion, who were randomized to treatment with 675 mg subcutaneous fremanezumab once monthly, or placebo. The average elapsed time since the trauma was 8.1 years in the placebo group and 9.3 years in the fremanezumab arm. The average number of moderate to severe headache days was 18.5 days in the placebo group and 18.4 days in the fremanezumab group. The initial 12-week randomized period was followed by an open-label period in which patients on placebo received the study drug.

After 12 weeks of treatment, there was a greater decrease in moderate to severe headache days in the placebo arm, though the difference was not statistically significant (–5.1 versus –3.6 days; P = .1876). At 1 month, the two groups were similar (–4 days placebo versus –3.6 days fremanezumab), but there was a greater reduction in the placebo arm at 2 months (–6.7 versus –3.7 days) and 3 months (–7.21 versus –5.2 days).

A secondary endpoint was the proportion of patients who experienced a 50% or greater reduction in moderate to severe headache days, and there was no significant difference between placebo and fremanezumab after 12 weeks (26% versus 21%) or at month 1 (26% versus 19%), month 2 (33% versus 19%), or month 3 (28% versus 33%).

Adverse events occurred more often in the placebo group (81% versus 72%), and all were mild or moderate, with the exception of one that occurred in the placebo group. There were no deaths, and no meaningful changes in laboratory or clinical examinations.

Dr. Spierings is on the advisory board for Satsuma, is a speaker for Teva, Amgen, Novartis, Eli Lilly, Lundbeck, Biohaven, and AbbVie, and has been a clinical trial principal investigator for Teva, Novartis, Eli Lilly, Biohaven, and Satsuma. Dr. Tepper has been a consultant for Teva. Dr. Rapoport has consulted for Teva and has been a speaker for Teva.

A phase 2 study of the anti-calcitonin gene–related peptide (CGRP) antibody fremanezumab found no benefit of treatment in persistent posttraumatic headache. Anti-CGRP therapy had been predicted to be effective, given its history of improving other forms of headache, and preclinical studies had suggested that CGRP plays a role in late pain sensitization that can occur after mild brain injuries.

“There was a decrease in migraine headache days of moderate or severe intensity in both groups. But the difference between fremanezumab and placebo treatment was not statistically significant, either looking at that on a monthly basis or over the total 12 weeks of treatment,” Egilius L.H. Spierings, MD, PhD, said during his presentation of the results at the American Headache Society’s 2021 annual meeting. Dr. Spierings is medical director of the Boston Headache Institute.
 

Disappointing findings

“That’s sad. It’s just dreadful news,” Stewart J. Tepper, MD, professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. Dr. Tepper was not involved in the study. The results suggest that CGRP mechanisms may not be relevant to persistent posttraumatic headache, but it could still play a role at onset. “We have to rethink this. Either it’s that chronic, persistent posttraumatic headache does not have a CGRP biology, or it’s that you have to get to them earlier [in the disease process],” he said.

The negative results were surprising, according to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and former president of the International Headache Society. He noted that the study was small, and the researchers were unable to conduct subgroup analyses. “Posttraumatic headaches are usually broken down into those that phenotypically look like migraine, or phenotypically look like tension-type headache. It would have been nice to know if most of them had what clinically appears to be tension-type headache, and maybe that’s why they didn’t respond. Or did most of them have a migraine phenotype, and then it would be a little more surprising that they didn’t respond,” Dr. Rapoport said in an interview.

As a result, he believes that further studies might show that fremanezumab is an effective treatment for posttraumatic headache. “I would not give up on it. I expect that a larger study with better power, and a better idea of exactly what was wrong with the patients, might end up being a positive study,” he said.

Although most posttraumatic headaches resolve within weeks or months, some can linger or become chronic for years. Pain medication is often prescribed but should not be, according to Dr. Rapoport, because it can lead to medication overuse headache that worsens the problem. “So we badly need a good temporary preventive treatment. The thought of giving our newest, most effective preventive medications, with few adverse events, is a good one. It just didn’t seem to work in this fairly small and underpowered study,” he said.
 

The phase 2 trial

The trial included 87 patients with new-onset or significant worsening of headache following a minor traumatic brain injury or concussion, who were randomized to treatment with 675 mg subcutaneous fremanezumab once monthly, or placebo. The average elapsed time since the trauma was 8.1 years in the placebo group and 9.3 years in the fremanezumab arm. The average number of moderate to severe headache days was 18.5 days in the placebo group and 18.4 days in the fremanezumab group. The initial 12-week randomized period was followed by an open-label period in which patients on placebo received the study drug.

After 12 weeks of treatment, there was a greater decrease in moderate to severe headache days in the placebo arm, though the difference was not statistically significant (–5.1 versus –3.6 days; P = .1876). At 1 month, the two groups were similar (–4 days placebo versus –3.6 days fremanezumab), but there was a greater reduction in the placebo arm at 2 months (–6.7 versus –3.7 days) and 3 months (–7.21 versus –5.2 days).

A secondary endpoint was the proportion of patients who experienced a 50% or greater reduction in moderate to severe headache days, and there was no significant difference between placebo and fremanezumab after 12 weeks (26% versus 21%) or at month 1 (26% versus 19%), month 2 (33% versus 19%), or month 3 (28% versus 33%).

Adverse events occurred more often in the placebo group (81% versus 72%), and all were mild or moderate, with the exception of one that occurred in the placebo group. There were no deaths, and no meaningful changes in laboratory or clinical examinations.

Dr. Spierings is on the advisory board for Satsuma, is a speaker for Teva, Amgen, Novartis, Eli Lilly, Lundbeck, Biohaven, and AbbVie, and has been a clinical trial principal investigator for Teva, Novartis, Eli Lilly, Biohaven, and Satsuma. Dr. Tepper has been a consultant for Teva. Dr. Rapoport has consulted for Teva and has been a speaker for Teva.

A phase 2 study of the anti-calcitonin gene–related peptide (CGRP) antibody fremanezumab found no benefit of treatment in persistent posttraumatic headache. Anti-CGRP therapy had been predicted to be effective, given its history of improving other forms of headache, and preclinical studies had suggested that CGRP plays a role in late pain sensitization that can occur after mild brain injuries.

“There was a decrease in migraine headache days of moderate or severe intensity in both groups. But the difference between fremanezumab and placebo treatment was not statistically significant, either looking at that on a monthly basis or over the total 12 weeks of treatment,” Egilius L.H. Spierings, MD, PhD, said during his presentation of the results at the American Headache Society’s 2021 annual meeting. Dr. Spierings is medical director of the Boston Headache Institute.
 

Disappointing findings

“That’s sad. It’s just dreadful news,” Stewart J. Tepper, MD, professor of neurology at Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. Dr. Tepper was not involved in the study. The results suggest that CGRP mechanisms may not be relevant to persistent posttraumatic headache, but it could still play a role at onset. “We have to rethink this. Either it’s that chronic, persistent posttraumatic headache does not have a CGRP biology, or it’s that you have to get to them earlier [in the disease process],” he said.

The negative results were surprising, according to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and former president of the International Headache Society. He noted that the study was small, and the researchers were unable to conduct subgroup analyses. “Posttraumatic headaches are usually broken down into those that phenotypically look like migraine, or phenotypically look like tension-type headache. It would have been nice to know if most of them had what clinically appears to be tension-type headache, and maybe that’s why they didn’t respond. Or did most of them have a migraine phenotype, and then it would be a little more surprising that they didn’t respond,” Dr. Rapoport said in an interview.

As a result, he believes that further studies might show that fremanezumab is an effective treatment for posttraumatic headache. “I would not give up on it. I expect that a larger study with better power, and a better idea of exactly what was wrong with the patients, might end up being a positive study,” he said.

Although most posttraumatic headaches resolve within weeks or months, some can linger or become chronic for years. Pain medication is often prescribed but should not be, according to Dr. Rapoport, because it can lead to medication overuse headache that worsens the problem. “So we badly need a good temporary preventive treatment. The thought of giving our newest, most effective preventive medications, with few adverse events, is a good one. It just didn’t seem to work in this fairly small and underpowered study,” he said.
 

The phase 2 trial

The trial included 87 patients with new-onset or significant worsening of headache following a minor traumatic brain injury or concussion, who were randomized to treatment with 675 mg subcutaneous fremanezumab once monthly, or placebo. The average elapsed time since the trauma was 8.1 years in the placebo group and 9.3 years in the fremanezumab arm. The average number of moderate to severe headache days was 18.5 days in the placebo group and 18.4 days in the fremanezumab group. The initial 12-week randomized period was followed by an open-label period in which patients on placebo received the study drug.

After 12 weeks of treatment, there was a greater decrease in moderate to severe headache days in the placebo arm, though the difference was not statistically significant (–5.1 versus –3.6 days; P = .1876). At 1 month, the two groups were similar (–4 days placebo versus –3.6 days fremanezumab), but there was a greater reduction in the placebo arm at 2 months (–6.7 versus –3.7 days) and 3 months (–7.21 versus –5.2 days).

A secondary endpoint was the proportion of patients who experienced a 50% or greater reduction in moderate to severe headache days, and there was no significant difference between placebo and fremanezumab after 12 weeks (26% versus 21%) or at month 1 (26% versus 19%), month 2 (33% versus 19%), or month 3 (28% versus 33%).

Adverse events occurred more often in the placebo group (81% versus 72%), and all were mild or moderate, with the exception of one that occurred in the placebo group. There were no deaths, and no meaningful changes in laboratory or clinical examinations.

Dr. Spierings is on the advisory board for Satsuma, is a speaker for Teva, Amgen, Novartis, Eli Lilly, Lundbeck, Biohaven, and AbbVie, and has been a clinical trial principal investigator for Teva, Novartis, Eli Lilly, Biohaven, and Satsuma. Dr. Tepper has been a consultant for Teva. Dr. Rapoport has consulted for Teva and has been a speaker for Teva.

Apparent migraines experienced by 19th century factory workers remain relevant to clinical medicine today. Those workers were employed in the manufacture of nitroglycerine, and many became patients of a physician who in 1880 described them as experiencing headache with nausea, vomiting, and walking lightly on their toes. A majority of patients were women.

When researchers in the 1950s worked out how to use nitroglycerine to trigger migraine-like headaches, the chemical became an important experimental tool, Peter Goadsby, MD, PhD, said during a talk on the translational importance of nitroglycerine in headache medicine at the American Headache Society’s 2021 annual meeting.

Some neurologists view nitroglycerine with skepticism, but that’s not necessarily warranted, said Dr. Goadsby. “To me, it’s underappreciated, but it has matured. If you were talking about this topic a decade ago, then the criticism would be that somehow that it’s not migraine, or it’s got nothing really to do with migraine,” he said in an interview.

But varying lines of clinical and experimental research have strengthened the case that nitroglycerine-induced migraine is largely indistinguishable from natural-onset migraine, and that studies that use it can provide important insights into patient management. “If I said to a colleague, ‘I’ve got this patient with headaches, and they’ve got nausea, and they’re sensitive to light. And if they move their head about, it’s worse,’ that sounds like migraine, and that’s what they’d say. The patients will tell you it’s the same, and they have the same premonitory symptoms. They respond to the same medicines,” said Dr. Goadsby.

The method is also one of the few available to study premonitory symptoms, since it is difficult to predict naturally-occurring migraines. Once the minimal dose of nitroglycerine dose to trigger an attack was worked out, researchers could use functional imaging to monitor what happens before and during the episode. To support this point, Dr. Goadsby cited a 2005 study in Brain by his own group. They used positron-emission tomography (PET) scans to conclude that lateralized brain dysfunction is associated with lateralized pain during migraine.

The premonitory stage is characterized by symptoms such as neck stiffness, cognitive impairment, mood alterations, and fatigue, as well as homeostatic symptoms such as sleepiness and polyuria. Other possible symptoms include photophobia, phonophobia, nausea, and cranial autonomic symptoms. These symptoms can be studied and established with the use of nitroglycerin trigger studies.

Dr. Goadsby pointed out that triggered episodes can also be used to test therapeutics. Calcitonin gene-related peptide receptor antagonists, 5-HT1F receptor agonists, and substance P/neurokinin 1 receptor antagonists have all been tested against nitroglycerine-induced migraines.

Other studies have used repeat exposures to nitroglycerine to better understand the effects of chronic migraines. Dr. Goadsby cited an example by researchers at the University of Illinois at Chicago led by Amynah Pradhan, PhD, which administered nitroglycerine repeatedly to mice and found that it led to acute mechanical hyperalgesia and basal hyperalgesia. The latter effect was dose dependent and persistent after nitroglycerine administration stopped. The phosphodiesterase inhibitor sildenafil, which can trigger migraines in humans, made the effect worse, suggesting that nitric oxide may be the mediator.

Apparent migraines experienced by 19th century factory workers remain relevant to clinical medicine today. Those workers were employed in the manufacture of nitroglycerine, and many became patients of a physician who in 1880 described them as experiencing headache with nausea, vomiting, and walking lightly on their toes. A majority of patients were women.

When researchers in the 1950s worked out how to use nitroglycerine to trigger migraine-like headaches, the chemical became an important experimental tool, Peter Goadsby, MD, PhD, said during a talk on the translational importance of nitroglycerine in headache medicine at the American Headache Society’s 2021 annual meeting.

Some neurologists view nitroglycerine with skepticism, but that’s not necessarily warranted, said Dr. Goadsby. “To me, it’s underappreciated, but it has matured. If you were talking about this topic a decade ago, then the criticism would be that somehow that it’s not migraine, or it’s got nothing really to do with migraine,” he said in an interview.

But varying lines of clinical and experimental research have strengthened the case that nitroglycerine-induced migraine is largely indistinguishable from natural-onset migraine, and that studies that use it can provide important insights into patient management. “If I said to a colleague, ‘I’ve got this patient with headaches, and they’ve got nausea, and they’re sensitive to light. And if they move their head about, it’s worse,’ that sounds like migraine, and that’s what they’d say. The patients will tell you it’s the same, and they have the same premonitory symptoms. They respond to the same medicines,” said Dr. Goadsby.

The method is also one of the few available to study premonitory symptoms, since it is difficult to predict naturally-occurring migraines. Once the minimal dose of nitroglycerine dose to trigger an attack was worked out, researchers could use functional imaging to monitor what happens before and during the episode. To support this point, Dr. Goadsby cited a 2005 study in Brain by his own group. They used positron-emission tomography (PET) scans to conclude that lateralized brain dysfunction is associated with lateralized pain during migraine.

The premonitory stage is characterized by symptoms such as neck stiffness, cognitive impairment, mood alterations, and fatigue, as well as homeostatic symptoms such as sleepiness and polyuria. Other possible symptoms include photophobia, phonophobia, nausea, and cranial autonomic symptoms. These symptoms can be studied and established with the use of nitroglycerin trigger studies.

Dr. Goadsby pointed out that triggered episodes can also be used to test therapeutics. Calcitonin gene-related peptide receptor antagonists, 5-HT1F receptor agonists, and substance P/neurokinin 1 receptor antagonists have all been tested against nitroglycerine-induced migraines.

Other studies have used repeat exposures to nitroglycerine to better understand the effects of chronic migraines. Dr. Goadsby cited an example by researchers at the University of Illinois at Chicago led by Amynah Pradhan, PhD, which administered nitroglycerine repeatedly to mice and found that it led to acute mechanical hyperalgesia and basal hyperalgesia. The latter effect was dose dependent and persistent after nitroglycerine administration stopped. The phosphodiesterase inhibitor sildenafil, which can trigger migraines in humans, made the effect worse, suggesting that nitric oxide may be the mediator.

Apparent migraines experienced by 19th century factory workers remain relevant to clinical medicine today. Those workers were employed in the manufacture of nitroglycerine, and many became patients of a physician who in 1880 described them as experiencing headache with nausea, vomiting, and walking lightly on their toes. A majority of patients were women.

When researchers in the 1950s worked out how to use nitroglycerine to trigger migraine-like headaches, the chemical became an important experimental tool, Peter Goadsby, MD, PhD, said during a talk on the translational importance of nitroglycerine in headache medicine at the American Headache Society’s 2021 annual meeting.

Some neurologists view nitroglycerine with skepticism, but that’s not necessarily warranted, said Dr. Goadsby. “To me, it’s underappreciated, but it has matured. If you were talking about this topic a decade ago, then the criticism would be that somehow that it’s not migraine, or it’s got nothing really to do with migraine,” he said in an interview.

But varying lines of clinical and experimental research have strengthened the case that nitroglycerine-induced migraine is largely indistinguishable from natural-onset migraine, and that studies that use it can provide important insights into patient management. “If I said to a colleague, ‘I’ve got this patient with headaches, and they’ve got nausea, and they’re sensitive to light. And if they move their head about, it’s worse,’ that sounds like migraine, and that’s what they’d say. The patients will tell you it’s the same, and they have the same premonitory symptoms. They respond to the same medicines,” said Dr. Goadsby.

The method is also one of the few available to study premonitory symptoms, since it is difficult to predict naturally-occurring migraines. Once the minimal dose of nitroglycerine dose to trigger an attack was worked out, researchers could use functional imaging to monitor what happens before and during the episode. To support this point, Dr. Goadsby cited a 2005 study in Brain by his own group. They used positron-emission tomography (PET) scans to conclude that lateralized brain dysfunction is associated with lateralized pain during migraine.

The premonitory stage is characterized by symptoms such as neck stiffness, cognitive impairment, mood alterations, and fatigue, as well as homeostatic symptoms such as sleepiness and polyuria. Other possible symptoms include photophobia, phonophobia, nausea, and cranial autonomic symptoms. These symptoms can be studied and established with the use of nitroglycerin trigger studies.

Dr. Goadsby pointed out that triggered episodes can also be used to test therapeutics. Calcitonin gene-related peptide receptor antagonists, 5-HT1F receptor agonists, and substance P/neurokinin 1 receptor antagonists have all been tested against nitroglycerine-induced migraines.

Other studies have used repeat exposures to nitroglycerine to better understand the effects of chronic migraines. Dr. Goadsby cited an example by researchers at the University of Illinois at Chicago led by Amynah Pradhan, PhD, which administered nitroglycerine repeatedly to mice and found that it led to acute mechanical hyperalgesia and basal hyperalgesia. The latter effect was dose dependent and persistent after nitroglycerine administration stopped. The phosphodiesterase inhibitor sildenafil, which can trigger migraines in humans, made the effect worse, suggesting that nitric oxide may be the mediator.