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Age does not appear to affect efficacy of siponimod in secondary progressive MS
WEST PALM BEACH, FLA. – (MS), according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Siponimod’s tolerability also does not vary with age, the researchers said.
Although many effective treatments for relapsing-remitting MS are available, patients still have a high risk of developing secondary progressive MS. Increasing age is associated with disability accumulation, regardless of disease duration. This accumulation of disability could affect treatment outcomes.
Siponimod is an approved treatment for adults with relapsing forms of MS, including clinically isolated syndrome and active secondary progressive MS. Compared with placebo, siponimod significantly reduced the risk of confirmed disability progression in the phase 3 EXPAND trial.
Efficacy was similar between age groups
Le Hua, MD, a neurologist at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, and colleagues sought to evaluate the safety and efficacy of siponimod by age in patients with active secondary progressive MS who participated in the EXPAND study. The investigators defined active disease as a relapse in the 2 years before screening or one or more T1 gadolinium–enhancing lesions at baseline. Time to 3- and 6-month confirmed disability progression, defined using Expanded Disability Status Scale (EDSS) scores, were the efficacy endpoints of this analysis. Dr. Hua and colleagues also examined adverse events, serious adverse events, and adverse events leading to treatment discontinuation.
Of the 1,651 patients included in EXPAND, 779 had active secondary progressive MS. Dr. Hua and colleagues categorized this group as younger than 45 years (306 patients) or 45 years or older (473 patients). In the overall EXPAND population, siponimod reduced the risk of 3-month confirmed disability progression by 21% and the risk of 6-month confirmed disability progression by 26%, compared with placebo. Among patients younger than 45 years, siponimod reduced the risks of 3- and 6-month confirmed disability progression by 32% and 40%, respectively. Among patients aged 45 years or older, siponimod reduced the risks of 3- and 6-month confirmed disability progression by 31% and 33%, respectively.
Siponimod’s safety profile was similar between age groups. Among participants younger than 45 years, the rate of any adverse event was 82.6% for siponimod and 82.8% for placebo. In patients age 45 years or older, the rate of any adverse event was 89.8% for siponimod and 75.9% for placebo. The rate of serious adverse events was lower for siponimod than for placebo in both age groups. Among patients younger than 45 years, the rate was 12.7% for siponimod and 15.1% for placebo. Among patients age 45 years or older, the rate was 18.2% for siponimod and 19.4% for placebo. The rate of adverse events leading to discontinuation, however, was slightly higher among older patients. For younger patients, the rate was 3.3% for siponimod and 4.3% for placebo. For older patients, the rate was 7.6% for siponimod and 7.1% for placebo.
Real-world data will provide clearer answers
Rates of adverse events, serious adverse events, and adverse events leading to discontinuation were all higher in patients aged 45 or older. “This was not a surprising finding,” said Dr. Hua. “The differences appeared small, and the study was not powered to detect if these differences were significant. ... In general, older patients are more likely to have more cardiac events and infections than younger patients.”
Few studies have analyzed the efficacy and safety of MS therapy by age, said Dr. Hua. In 2015, Matell et al. evaluated the effectiveness of natalizumab in patients over age 50 years. In that study, a greater number of older patients, compared with younger patients, stopped treatment because of lack of effectiveness. Studies of other disease-modifying therapies (DMTs) have included subgroup analyses based on age, “but subgroup analyses are limited in the ability to make any strong conclusions regarding significant differences in safety,” said Dr. Hua. “A recent meta-analysis of published clinical trials of all DMTs performed by Weideman et al. indicated that the efficacy of DMTs appears to wane after age 53 years. However, there are limitations in interpreting this data, as they weren’t able to evaluate the raw data. And in most clinical trials, the age cutoff is usually 55 years, which limits generalizations. Real-world data analyses are needed to truly understand efficacy and safety of DMT in older patients.”
Novartis funded the study. Dr. Hua received fees from Novartis, Biogen, Celgene, EMD Serono, Genentech, and Genzyme.
SOURCE: Hua L et al. ACTRIMS FORUM 2020, Abstract P029.
WEST PALM BEACH, FLA. – (MS), according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Siponimod’s tolerability also does not vary with age, the researchers said.
Although many effective treatments for relapsing-remitting MS are available, patients still have a high risk of developing secondary progressive MS. Increasing age is associated with disability accumulation, regardless of disease duration. This accumulation of disability could affect treatment outcomes.
Siponimod is an approved treatment for adults with relapsing forms of MS, including clinically isolated syndrome and active secondary progressive MS. Compared with placebo, siponimod significantly reduced the risk of confirmed disability progression in the phase 3 EXPAND trial.
Efficacy was similar between age groups
Le Hua, MD, a neurologist at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, and colleagues sought to evaluate the safety and efficacy of siponimod by age in patients with active secondary progressive MS who participated in the EXPAND study. The investigators defined active disease as a relapse in the 2 years before screening or one or more T1 gadolinium–enhancing lesions at baseline. Time to 3- and 6-month confirmed disability progression, defined using Expanded Disability Status Scale (EDSS) scores, were the efficacy endpoints of this analysis. Dr. Hua and colleagues also examined adverse events, serious adverse events, and adverse events leading to treatment discontinuation.
Of the 1,651 patients included in EXPAND, 779 had active secondary progressive MS. Dr. Hua and colleagues categorized this group as younger than 45 years (306 patients) or 45 years or older (473 patients). In the overall EXPAND population, siponimod reduced the risk of 3-month confirmed disability progression by 21% and the risk of 6-month confirmed disability progression by 26%, compared with placebo. Among patients younger than 45 years, siponimod reduced the risks of 3- and 6-month confirmed disability progression by 32% and 40%, respectively. Among patients aged 45 years or older, siponimod reduced the risks of 3- and 6-month confirmed disability progression by 31% and 33%, respectively.
Siponimod’s safety profile was similar between age groups. Among participants younger than 45 years, the rate of any adverse event was 82.6% for siponimod and 82.8% for placebo. In patients age 45 years or older, the rate of any adverse event was 89.8% for siponimod and 75.9% for placebo. The rate of serious adverse events was lower for siponimod than for placebo in both age groups. Among patients younger than 45 years, the rate was 12.7% for siponimod and 15.1% for placebo. Among patients age 45 years or older, the rate was 18.2% for siponimod and 19.4% for placebo. The rate of adverse events leading to discontinuation, however, was slightly higher among older patients. For younger patients, the rate was 3.3% for siponimod and 4.3% for placebo. For older patients, the rate was 7.6% for siponimod and 7.1% for placebo.
Real-world data will provide clearer answers
Rates of adverse events, serious adverse events, and adverse events leading to discontinuation were all higher in patients aged 45 or older. “This was not a surprising finding,” said Dr. Hua. “The differences appeared small, and the study was not powered to detect if these differences were significant. ... In general, older patients are more likely to have more cardiac events and infections than younger patients.”
Few studies have analyzed the efficacy and safety of MS therapy by age, said Dr. Hua. In 2015, Matell et al. evaluated the effectiveness of natalizumab in patients over age 50 years. In that study, a greater number of older patients, compared with younger patients, stopped treatment because of lack of effectiveness. Studies of other disease-modifying therapies (DMTs) have included subgroup analyses based on age, “but subgroup analyses are limited in the ability to make any strong conclusions regarding significant differences in safety,” said Dr. Hua. “A recent meta-analysis of published clinical trials of all DMTs performed by Weideman et al. indicated that the efficacy of DMTs appears to wane after age 53 years. However, there are limitations in interpreting this data, as they weren’t able to evaluate the raw data. And in most clinical trials, the age cutoff is usually 55 years, which limits generalizations. Real-world data analyses are needed to truly understand efficacy and safety of DMT in older patients.”
Novartis funded the study. Dr. Hua received fees from Novartis, Biogen, Celgene, EMD Serono, Genentech, and Genzyme.
SOURCE: Hua L et al. ACTRIMS FORUM 2020, Abstract P029.
WEST PALM BEACH, FLA. – (MS), according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Siponimod’s tolerability also does not vary with age, the researchers said.
Although many effective treatments for relapsing-remitting MS are available, patients still have a high risk of developing secondary progressive MS. Increasing age is associated with disability accumulation, regardless of disease duration. This accumulation of disability could affect treatment outcomes.
Siponimod is an approved treatment for adults with relapsing forms of MS, including clinically isolated syndrome and active secondary progressive MS. Compared with placebo, siponimod significantly reduced the risk of confirmed disability progression in the phase 3 EXPAND trial.
Efficacy was similar between age groups
Le Hua, MD, a neurologist at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, and colleagues sought to evaluate the safety and efficacy of siponimod by age in patients with active secondary progressive MS who participated in the EXPAND study. The investigators defined active disease as a relapse in the 2 years before screening or one or more T1 gadolinium–enhancing lesions at baseline. Time to 3- and 6-month confirmed disability progression, defined using Expanded Disability Status Scale (EDSS) scores, were the efficacy endpoints of this analysis. Dr. Hua and colleagues also examined adverse events, serious adverse events, and adverse events leading to treatment discontinuation.
Of the 1,651 patients included in EXPAND, 779 had active secondary progressive MS. Dr. Hua and colleagues categorized this group as younger than 45 years (306 patients) or 45 years or older (473 patients). In the overall EXPAND population, siponimod reduced the risk of 3-month confirmed disability progression by 21% and the risk of 6-month confirmed disability progression by 26%, compared with placebo. Among patients younger than 45 years, siponimod reduced the risks of 3- and 6-month confirmed disability progression by 32% and 40%, respectively. Among patients aged 45 years or older, siponimod reduced the risks of 3- and 6-month confirmed disability progression by 31% and 33%, respectively.
Siponimod’s safety profile was similar between age groups. Among participants younger than 45 years, the rate of any adverse event was 82.6% for siponimod and 82.8% for placebo. In patients age 45 years or older, the rate of any adverse event was 89.8% for siponimod and 75.9% for placebo. The rate of serious adverse events was lower for siponimod than for placebo in both age groups. Among patients younger than 45 years, the rate was 12.7% for siponimod and 15.1% for placebo. Among patients age 45 years or older, the rate was 18.2% for siponimod and 19.4% for placebo. The rate of adverse events leading to discontinuation, however, was slightly higher among older patients. For younger patients, the rate was 3.3% for siponimod and 4.3% for placebo. For older patients, the rate was 7.6% for siponimod and 7.1% for placebo.
Real-world data will provide clearer answers
Rates of adverse events, serious adverse events, and adverse events leading to discontinuation were all higher in patients aged 45 or older. “This was not a surprising finding,” said Dr. Hua. “The differences appeared small, and the study was not powered to detect if these differences were significant. ... In general, older patients are more likely to have more cardiac events and infections than younger patients.”
Few studies have analyzed the efficacy and safety of MS therapy by age, said Dr. Hua. In 2015, Matell et al. evaluated the effectiveness of natalizumab in patients over age 50 years. In that study, a greater number of older patients, compared with younger patients, stopped treatment because of lack of effectiveness. Studies of other disease-modifying therapies (DMTs) have included subgroup analyses based on age, “but subgroup analyses are limited in the ability to make any strong conclusions regarding significant differences in safety,” said Dr. Hua. “A recent meta-analysis of published clinical trials of all DMTs performed by Weideman et al. indicated that the efficacy of DMTs appears to wane after age 53 years. However, there are limitations in interpreting this data, as they weren’t able to evaluate the raw data. And in most clinical trials, the age cutoff is usually 55 years, which limits generalizations. Real-world data analyses are needed to truly understand efficacy and safety of DMT in older patients.”
Novartis funded the study. Dr. Hua received fees from Novartis, Biogen, Celgene, EMD Serono, Genentech, and Genzyme.
SOURCE: Hua L et al. ACTRIMS FORUM 2020, Abstract P029.
REPORTING FROM ACTRIMS FORUM 2020
Hyperlipidemia occurs earlier in patients with MS
WEST PALM BEACH, FLA. – Onset of hyperlipidemia tends to occur earlier in patients with multiple sclerosis (MS), compared with matched controls, according to new research. Among females and African Americans, the effect of MS on age of hyperlipidemia onset may be especially pronounced, said Diane Krill, PhD, professor of biological sciences at Point Park University, Pittsburgh, and colleagues.
Many patients with MS have hyperlipidemia, and adverse lipid profiles correlate with physical and cognitive impairment in this population. “There is evidence of endothelial dysfunction and inflammation in both MS and hyperlipidemia, but the timing of onset of hyperlipidemia is not known,” the researchers said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To assess whether patients with MS have hyperlipidemia diagnosed at an earlier age, relative to matched controls, Dr. Krill and colleagues analyzed data from the Cleveland Clinic health system. They included in their analyses patients with at least two hyperlipidemia diagnoses and at least five encounters with a primary care physician. They matched each patient with MS to four patients without MS using variables such as birth year, sex, race, and year of first encounter. In all, the study included 669 patients with MS and 2,676 controls. The investigators examined age of hyperlipidemia onset using multivariable Cox proportional hazard models that adjusted for sex, race, smoking, and body mass index.
Patients with MS had a 20% increased risk for earlier onset of hyperlipidemia, relative to matched controls. The effect was greater among females (hazard ratio, 1.22) and African Americans (HR, 1.42). Patients with MS have earlier onset of hyperlipidemia “irrespective of the relationship with age of MS onset,” Dr. Krill and colleagues noted. “Additional research is warranted to further characterize the temporal relationships between MS and hyperlipidemia, as well as considerations for timing of disease-modifying therapies.”
The researchers had no relevant disclosures.
SOURCE: Krill D et al. ACTRIMS Forum 2020, Abstract P085.
WEST PALM BEACH, FLA. – Onset of hyperlipidemia tends to occur earlier in patients with multiple sclerosis (MS), compared with matched controls, according to new research. Among females and African Americans, the effect of MS on age of hyperlipidemia onset may be especially pronounced, said Diane Krill, PhD, professor of biological sciences at Point Park University, Pittsburgh, and colleagues.
Many patients with MS have hyperlipidemia, and adverse lipid profiles correlate with physical and cognitive impairment in this population. “There is evidence of endothelial dysfunction and inflammation in both MS and hyperlipidemia, but the timing of onset of hyperlipidemia is not known,” the researchers said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To assess whether patients with MS have hyperlipidemia diagnosed at an earlier age, relative to matched controls, Dr. Krill and colleagues analyzed data from the Cleveland Clinic health system. They included in their analyses patients with at least two hyperlipidemia diagnoses and at least five encounters with a primary care physician. They matched each patient with MS to four patients without MS using variables such as birth year, sex, race, and year of first encounter. In all, the study included 669 patients with MS and 2,676 controls. The investigators examined age of hyperlipidemia onset using multivariable Cox proportional hazard models that adjusted for sex, race, smoking, and body mass index.
Patients with MS had a 20% increased risk for earlier onset of hyperlipidemia, relative to matched controls. The effect was greater among females (hazard ratio, 1.22) and African Americans (HR, 1.42). Patients with MS have earlier onset of hyperlipidemia “irrespective of the relationship with age of MS onset,” Dr. Krill and colleagues noted. “Additional research is warranted to further characterize the temporal relationships between MS and hyperlipidemia, as well as considerations for timing of disease-modifying therapies.”
The researchers had no relevant disclosures.
SOURCE: Krill D et al. ACTRIMS Forum 2020, Abstract P085.
WEST PALM BEACH, FLA. – Onset of hyperlipidemia tends to occur earlier in patients with multiple sclerosis (MS), compared with matched controls, according to new research. Among females and African Americans, the effect of MS on age of hyperlipidemia onset may be especially pronounced, said Diane Krill, PhD, professor of biological sciences at Point Park University, Pittsburgh, and colleagues.
Many patients with MS have hyperlipidemia, and adverse lipid profiles correlate with physical and cognitive impairment in this population. “There is evidence of endothelial dysfunction and inflammation in both MS and hyperlipidemia, but the timing of onset of hyperlipidemia is not known,” the researchers said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To assess whether patients with MS have hyperlipidemia diagnosed at an earlier age, relative to matched controls, Dr. Krill and colleagues analyzed data from the Cleveland Clinic health system. They included in their analyses patients with at least two hyperlipidemia diagnoses and at least five encounters with a primary care physician. They matched each patient with MS to four patients without MS using variables such as birth year, sex, race, and year of first encounter. In all, the study included 669 patients with MS and 2,676 controls. The investigators examined age of hyperlipidemia onset using multivariable Cox proportional hazard models that adjusted for sex, race, smoking, and body mass index.
Patients with MS had a 20% increased risk for earlier onset of hyperlipidemia, relative to matched controls. The effect was greater among females (hazard ratio, 1.22) and African Americans (HR, 1.42). Patients with MS have earlier onset of hyperlipidemia “irrespective of the relationship with age of MS onset,” Dr. Krill and colleagues noted. “Additional research is warranted to further characterize the temporal relationships between MS and hyperlipidemia, as well as considerations for timing of disease-modifying therapies.”
The researchers had no relevant disclosures.
SOURCE: Krill D et al. ACTRIMS Forum 2020, Abstract P085.
REPORTING FROM ACTRIMS FORUM 2020
Shared medical appointments educate and encourage MS patients
WEST PALM BEACH, FLA. – according to a presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis.
“At first, this may sound to patients like an awkward concept – they may say, ‘Why would I want to have a medical appointment with other people?’ ” Mary R. Rensel, MD, who is the director of the program at the Mellen Center for Multiple Sclerosis, Cleveland Clinic Foundation, said. “But once they get there, it’s wonderful to see what happens – patients start to encourage each other and share resources, and it’s enjoyable for the patients and providers alike,” she said.
The main objective of the shared appointments concept was to increase education regarding comorbidity prevention and management of MS, however, importantly, if patients wish to discuss any issues privately, they are accommodated. In addition, family members, children, and caregivers are all welcome to attend. “Caregivers need support as well, so their participation is welcome,” Dr. Rensel said.
A significant benefit of the program is the extended time with providers – an hour and a half – which is a substantially longer period than patients and providers typically spend together, Dr. Rensel noted. “Medical visits are often so rushed, but this gives us much more time together, to learn more and talk about things like brain health,” she said.
With guidance from a multidisciplinary team including nurses, wellness providers, psychologists, and other experts, there are currently seven meeting themes that are rotated through the year, focusing on a variety of subjects. One, for instance, includes education from a nutritionist, and the center includes a kitchen for the group to learn about and try recipes. Other sessions include chair yoga, art therapy, guided imagery, and exercise physiology.
The Cleveland Clinic is a leader in the concept of SMA and offers it to as many as 360 disease states. With the pilot program now underway for more than 3 years, Dr. Rensel and her team conducted a study to investigate its effects.
For the study, the authors collected clinical data on 50 patients who had attended at least one session between January 2016 and June 2019. Among the patients, 94% were female, 80% had relapsing-remitting MS, and mean age was 50. Patients had a mean Determined Disease Steps (PDSS) score of 3.1 plus or minus 2.4 and the average 25-foot walk and nine-hole peg test (dominant hand) times were 9.4 plus or minus 7.8 seconds and 25.8 plus or minus 9.1 seconds, respectively.
The most common comorbidity was depression/anxiety, occurring in 44% of patients, however after participation in the shared medical appointment program, their mean Patient Health Questionnaire-9 scores, with higher scores indicative of worse depression, decreased from pretreatment scores of 7.3 plus or minus 5.5 to posttreatment scores of 5.1 plus or minus 5.6 (P = .001).
Notably, the program appears to have had a positive effect on patients’ use of health care services – while there was a significant decrease in the mean number of emergency room visits (n = 13 to n = 2; P = .0005), the results showed a favorable increase in mean number of follow-up visits with attendees’ primary care providers (n = 19 to n = 41; P = 3.47), physical therapists (n = 15 to n = 27; P = .004), or psychologists (n = 6 to n = 19; P = .003).
“The study was to evaluate the effect of the program after even just one appointment, and we found it really seemed to increase the use of more appropriate care, with less ER utilization and more visits to primary care,” Dr. Rensel said. The study even showed a small but significant reduction in pre- and postoutcome body mass index (BMI, 30.2 plus or minus 7.3 vs. 28.8 plus or minus 7.1; P = .03).
A critical metric that was not measured in the study – the effect of social interaction and camaraderie in a condition that can, for many, feel socially isolating – is clearly profound, Dr. Rensel said.
Amar Dhand, MD, associate professor of neurology at Brigham and Women’s Hospital, Harvard University, Boston, agreed that the peer support in such medical group settings can be highly valuable.
“Shared medical appointments offer an opportunity for peer-to-peer engagement, support, and education,” he said in an interview. “For many patients, this is a chance to bond with persons who are coexperiencing similar problems, allowing new social connections to emerge.”
Dr. Dhand, who spoke on the issue of the importance of social networks at the meeting, noted that, although there are numerous benefits with shared medical appointments, not all patients may respond well.
“Health care settings are one place to stimulate community among peers. This is one important ingredient of addressing social isolation,” he said. “However, there remain challenges such as sustainability of such relationships, paradoxical depression when persons see others with more severe disease, and infrastructure to support such programs.”
The findings from the study, however, do suggest favorable responses, he noted.
“I think, mechanistically, improved psychosocial outcomes are the most pertinent to the intervention,” Dr. Dhand said. “The health care utilization may be attributed to other factors and will need to be assessed in a case control design.”
Key benefits of the shared medical appointment concept
A recent article from Cleveland Clinic researchers reviewing the concept of shared medical appointments summarizes that the programs offer benefits based on nine key principles:
- Group exposure in shared medical appointments combats isolation, which in turn helps to remove doubts about one’s ability to manage illness.
- Patients learn about disease self-management vicariously by witnessing others’ illness experiences.
- Patients feel inspired by seeing others who are coping well.
- Group dynamics lead patients and providers to developing more equitable relationships.
- Providers feel increased appreciation and rapport toward colleagues leading to increased efficiency.
- Providers learn from the patients how better to meet their patients’ needs.
- Adequate time allotment of the SMA leads patients to feel supported.
- Patients receive professional expertise from the provider in combination with firsthand information from peers, resulting in more robust health knowledge.
- Patients have the opportunity to see how the physicians interact with fellow patients, which allows them to get to know the physician and better determine their level of trust.
The take-home message from the shared medical appointments concept is that “it may hit a quadruple aim,” Dr. Rensel said. “Access, cost, outcomes, and provider satisfaction.”
The Shared Medical Appointments program received a grant from Genzyme. Dr. Rensel reported consulting or advisory board relationships with Serono, Biogen, Teva, Genzyme, Novartis, and the National Multiple Sclerosis Society. Dr. Dhand had no disclosures to report.
WEST PALM BEACH, FLA. – according to a presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis.
“At first, this may sound to patients like an awkward concept – they may say, ‘Why would I want to have a medical appointment with other people?’ ” Mary R. Rensel, MD, who is the director of the program at the Mellen Center for Multiple Sclerosis, Cleveland Clinic Foundation, said. “But once they get there, it’s wonderful to see what happens – patients start to encourage each other and share resources, and it’s enjoyable for the patients and providers alike,” she said.
The main objective of the shared appointments concept was to increase education regarding comorbidity prevention and management of MS, however, importantly, if patients wish to discuss any issues privately, they are accommodated. In addition, family members, children, and caregivers are all welcome to attend. “Caregivers need support as well, so their participation is welcome,” Dr. Rensel said.
A significant benefit of the program is the extended time with providers – an hour and a half – which is a substantially longer period than patients and providers typically spend together, Dr. Rensel noted. “Medical visits are often so rushed, but this gives us much more time together, to learn more and talk about things like brain health,” she said.
With guidance from a multidisciplinary team including nurses, wellness providers, psychologists, and other experts, there are currently seven meeting themes that are rotated through the year, focusing on a variety of subjects. One, for instance, includes education from a nutritionist, and the center includes a kitchen for the group to learn about and try recipes. Other sessions include chair yoga, art therapy, guided imagery, and exercise physiology.
The Cleveland Clinic is a leader in the concept of SMA and offers it to as many as 360 disease states. With the pilot program now underway for more than 3 years, Dr. Rensel and her team conducted a study to investigate its effects.
For the study, the authors collected clinical data on 50 patients who had attended at least one session between January 2016 and June 2019. Among the patients, 94% were female, 80% had relapsing-remitting MS, and mean age was 50. Patients had a mean Determined Disease Steps (PDSS) score of 3.1 plus or minus 2.4 and the average 25-foot walk and nine-hole peg test (dominant hand) times were 9.4 plus or minus 7.8 seconds and 25.8 plus or minus 9.1 seconds, respectively.
The most common comorbidity was depression/anxiety, occurring in 44% of patients, however after participation in the shared medical appointment program, their mean Patient Health Questionnaire-9 scores, with higher scores indicative of worse depression, decreased from pretreatment scores of 7.3 plus or minus 5.5 to posttreatment scores of 5.1 plus or minus 5.6 (P = .001).
Notably, the program appears to have had a positive effect on patients’ use of health care services – while there was a significant decrease in the mean number of emergency room visits (n = 13 to n = 2; P = .0005), the results showed a favorable increase in mean number of follow-up visits with attendees’ primary care providers (n = 19 to n = 41; P = 3.47), physical therapists (n = 15 to n = 27; P = .004), or psychologists (n = 6 to n = 19; P = .003).
“The study was to evaluate the effect of the program after even just one appointment, and we found it really seemed to increase the use of more appropriate care, with less ER utilization and more visits to primary care,” Dr. Rensel said. The study even showed a small but significant reduction in pre- and postoutcome body mass index (BMI, 30.2 plus or minus 7.3 vs. 28.8 plus or minus 7.1; P = .03).
A critical metric that was not measured in the study – the effect of social interaction and camaraderie in a condition that can, for many, feel socially isolating – is clearly profound, Dr. Rensel said.
Amar Dhand, MD, associate professor of neurology at Brigham and Women’s Hospital, Harvard University, Boston, agreed that the peer support in such medical group settings can be highly valuable.
“Shared medical appointments offer an opportunity for peer-to-peer engagement, support, and education,” he said in an interview. “For many patients, this is a chance to bond with persons who are coexperiencing similar problems, allowing new social connections to emerge.”
Dr. Dhand, who spoke on the issue of the importance of social networks at the meeting, noted that, although there are numerous benefits with shared medical appointments, not all patients may respond well.
“Health care settings are one place to stimulate community among peers. This is one important ingredient of addressing social isolation,” he said. “However, there remain challenges such as sustainability of such relationships, paradoxical depression when persons see others with more severe disease, and infrastructure to support such programs.”
The findings from the study, however, do suggest favorable responses, he noted.
“I think, mechanistically, improved psychosocial outcomes are the most pertinent to the intervention,” Dr. Dhand said. “The health care utilization may be attributed to other factors and will need to be assessed in a case control design.”
Key benefits of the shared medical appointment concept
A recent article from Cleveland Clinic researchers reviewing the concept of shared medical appointments summarizes that the programs offer benefits based on nine key principles:
- Group exposure in shared medical appointments combats isolation, which in turn helps to remove doubts about one’s ability to manage illness.
- Patients learn about disease self-management vicariously by witnessing others’ illness experiences.
- Patients feel inspired by seeing others who are coping well.
- Group dynamics lead patients and providers to developing more equitable relationships.
- Providers feel increased appreciation and rapport toward colleagues leading to increased efficiency.
- Providers learn from the patients how better to meet their patients’ needs.
- Adequate time allotment of the SMA leads patients to feel supported.
- Patients receive professional expertise from the provider in combination with firsthand information from peers, resulting in more robust health knowledge.
- Patients have the opportunity to see how the physicians interact with fellow patients, which allows them to get to know the physician and better determine their level of trust.
The take-home message from the shared medical appointments concept is that “it may hit a quadruple aim,” Dr. Rensel said. “Access, cost, outcomes, and provider satisfaction.”
The Shared Medical Appointments program received a grant from Genzyme. Dr. Rensel reported consulting or advisory board relationships with Serono, Biogen, Teva, Genzyme, Novartis, and the National Multiple Sclerosis Society. Dr. Dhand had no disclosures to report.
WEST PALM BEACH, FLA. – according to a presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis.
“At first, this may sound to patients like an awkward concept – they may say, ‘Why would I want to have a medical appointment with other people?’ ” Mary R. Rensel, MD, who is the director of the program at the Mellen Center for Multiple Sclerosis, Cleveland Clinic Foundation, said. “But once they get there, it’s wonderful to see what happens – patients start to encourage each other and share resources, and it’s enjoyable for the patients and providers alike,” she said.
The main objective of the shared appointments concept was to increase education regarding comorbidity prevention and management of MS, however, importantly, if patients wish to discuss any issues privately, they are accommodated. In addition, family members, children, and caregivers are all welcome to attend. “Caregivers need support as well, so their participation is welcome,” Dr. Rensel said.
A significant benefit of the program is the extended time with providers – an hour and a half – which is a substantially longer period than patients and providers typically spend together, Dr. Rensel noted. “Medical visits are often so rushed, but this gives us much more time together, to learn more and talk about things like brain health,” she said.
With guidance from a multidisciplinary team including nurses, wellness providers, psychologists, and other experts, there are currently seven meeting themes that are rotated through the year, focusing on a variety of subjects. One, for instance, includes education from a nutritionist, and the center includes a kitchen for the group to learn about and try recipes. Other sessions include chair yoga, art therapy, guided imagery, and exercise physiology.
The Cleveland Clinic is a leader in the concept of SMA and offers it to as many as 360 disease states. With the pilot program now underway for more than 3 years, Dr. Rensel and her team conducted a study to investigate its effects.
For the study, the authors collected clinical data on 50 patients who had attended at least one session between January 2016 and June 2019. Among the patients, 94% were female, 80% had relapsing-remitting MS, and mean age was 50. Patients had a mean Determined Disease Steps (PDSS) score of 3.1 plus or minus 2.4 and the average 25-foot walk and nine-hole peg test (dominant hand) times were 9.4 plus or minus 7.8 seconds and 25.8 plus or minus 9.1 seconds, respectively.
The most common comorbidity was depression/anxiety, occurring in 44% of patients, however after participation in the shared medical appointment program, their mean Patient Health Questionnaire-9 scores, with higher scores indicative of worse depression, decreased from pretreatment scores of 7.3 plus or minus 5.5 to posttreatment scores of 5.1 plus or minus 5.6 (P = .001).
Notably, the program appears to have had a positive effect on patients’ use of health care services – while there was a significant decrease in the mean number of emergency room visits (n = 13 to n = 2; P = .0005), the results showed a favorable increase in mean number of follow-up visits with attendees’ primary care providers (n = 19 to n = 41; P = 3.47), physical therapists (n = 15 to n = 27; P = .004), or psychologists (n = 6 to n = 19; P = .003).
“The study was to evaluate the effect of the program after even just one appointment, and we found it really seemed to increase the use of more appropriate care, with less ER utilization and more visits to primary care,” Dr. Rensel said. The study even showed a small but significant reduction in pre- and postoutcome body mass index (BMI, 30.2 plus or minus 7.3 vs. 28.8 plus or minus 7.1; P = .03).
A critical metric that was not measured in the study – the effect of social interaction and camaraderie in a condition that can, for many, feel socially isolating – is clearly profound, Dr. Rensel said.
Amar Dhand, MD, associate professor of neurology at Brigham and Women’s Hospital, Harvard University, Boston, agreed that the peer support in such medical group settings can be highly valuable.
“Shared medical appointments offer an opportunity for peer-to-peer engagement, support, and education,” he said in an interview. “For many patients, this is a chance to bond with persons who are coexperiencing similar problems, allowing new social connections to emerge.”
Dr. Dhand, who spoke on the issue of the importance of social networks at the meeting, noted that, although there are numerous benefits with shared medical appointments, not all patients may respond well.
“Health care settings are one place to stimulate community among peers. This is one important ingredient of addressing social isolation,” he said. “However, there remain challenges such as sustainability of such relationships, paradoxical depression when persons see others with more severe disease, and infrastructure to support such programs.”
The findings from the study, however, do suggest favorable responses, he noted.
“I think, mechanistically, improved psychosocial outcomes are the most pertinent to the intervention,” Dr. Dhand said. “The health care utilization may be attributed to other factors and will need to be assessed in a case control design.”
Key benefits of the shared medical appointment concept
A recent article from Cleveland Clinic researchers reviewing the concept of shared medical appointments summarizes that the programs offer benefits based on nine key principles:
- Group exposure in shared medical appointments combats isolation, which in turn helps to remove doubts about one’s ability to manage illness.
- Patients learn about disease self-management vicariously by witnessing others’ illness experiences.
- Patients feel inspired by seeing others who are coping well.
- Group dynamics lead patients and providers to developing more equitable relationships.
- Providers feel increased appreciation and rapport toward colleagues leading to increased efficiency.
- Providers learn from the patients how better to meet their patients’ needs.
- Adequate time allotment of the SMA leads patients to feel supported.
- Patients receive professional expertise from the provider in combination with firsthand information from peers, resulting in more robust health knowledge.
- Patients have the opportunity to see how the physicians interact with fellow patients, which allows them to get to know the physician and better determine their level of trust.
The take-home message from the shared medical appointments concept is that “it may hit a quadruple aim,” Dr. Rensel said. “Access, cost, outcomes, and provider satisfaction.”
The Shared Medical Appointments program received a grant from Genzyme. Dr. Rensel reported consulting or advisory board relationships with Serono, Biogen, Teva, Genzyme, Novartis, and the National Multiple Sclerosis Society. Dr. Dhand had no disclosures to report.
REPORTING FROM ACTRIMS FORUM 2020
Incomplete MS relapse recovery predicted greater long-term disability
WEST PALM BEACH, FLA. – Failure to recover completely from early relapses in multiple sclerosis (MS) is significantly associated with higher long-term disability, according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Incomplete recovery thus should be given more consideration when evaluating research and clinical practice outcomes, the study investigators cautioned.
“We found that the recovery from early relapses is an important predictor of future disability,” first author Marinos G. Sotiropoulos, MD, of the department of neurology, Brigham and Women’s Hospital, Boston, said in an interview. “It should be incorporated in future predictive models of disease severity and clinical trials, [and] it could be useful in clinical decision making as well.”
Incomplete recovery from relapses is known to be linked to disability progression and to the likelihood of transitioning to secondary progressive MS. Research on its role in longer-term outcomes is lacking, however.
To investigate the effect of incomplete relapse recovery in the first 3 years of MS on rates of disability at 10 years, Dr. Sotiropoulos and colleagues evaluated data on 360 patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation in Multiple Sclerosis at Brigham and Women’s Hospital) study. CLIMB is a natural history study spanning 20 years, with more than 2,000 patients.
Patients were included if at least 8.5 years had passed since their first documented symptom, if they were at least 18 years at their first visit to the Partners MS Center, if that visit occurred within 1 year of their first symptom, and if they had a diagnosis of relapsing-remitting MS or secondary progressive MS.
Among the 308 patients included in the study, 74% were female and 89% were white, with a mean age at the first symptom of 35.9 years.
A total of 403 early attacks from those 308 patients were included in the study. Half of the attacks (50.4%) were followed by incomplete recovery after 6 months, defined specifically as an increase in the Expanded Disability Status Scale (EDSS) scores from baseline to at least 6 months after the onset of the attack.
As of their 10-year visit, 27.3% of patients had a normal examination, defined as EDSS 0, and 64.1% had no significant disability (EDSS less than 2). The mean EDSS at 10 years was 1.52.
Patients’ recovery index, defined as the percentage of early attacks that recovered completely, was significantly associated with 10-year EDSS scores (P less than .001).
Patient age at first symptom was also a significant predictor of 10-year disability (P less than .004). Factors that were significantly associated with incomplete relapse recovery were the duration of time from first symptom (P less than .001) and moderate severity of the relapse (P = .029).
With the type of drug treatment likely representing an important factor in whether a patient has incomplete relapse recovery, the issue should be the subject of further research, Dr. Sotiropoulos said.
“This is something that is important to look at because none of the clinical trials for the drugs we currently have looked at relapse recovery as an outcome,” he explained.
“There have been some post hoc analyses [that] have shown that some of the new medications can improve recovery from relapses, but there is a lot to look into now that we know relapse recovery is an important clinical parameter,” he said. “We have to factor in the treatment effect in preventing residual disability after relapses.”
The findings suggest that “patients with incomplete early recovery might be considered for highly effective disease-modifying therapy,” added senior author Tanuja Chitnis, MD, also of the department of neurology at Brigham and Women’s Hospital. “We are now analyzing the biological mechanisms associated with relapse recovery.”
The authors of a recent study that echoes the importance of relapse recovery call it “the forgotten variable in multiple sclerosis clinical trials.” In that study, the researchers found an increased likelihood of a benign disease course among patients who received immediate disease-modifying therapy (DMT) initiation after failing to have a good recovery from an initial relapse (Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17;7[2]).
“Some clinicians may choose to hold off DMTs because the patient may not have high disease activity levels,” Burcu Zeydan, MD, a coauthor of that study and an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic, Rochester, Minn., said in an interview.
“What these studies add is that, if a patient is a poor recoverer despite not having highly active disease, that patient should be considered for immediate treatment initiation,” she said. “Otherwise, there is the possibility of a next relapse, which may not happen often. But when it happens, it may lead to more residual deficit with additional disability burden.”
The CLIMB study received funding from Mallinckrodt and the National MS Society Nancy Davis Center Without Walls. Dr. Sotiropoulos has received research support from Mallinckrodt. Dr. Chitnis has served on advisory boards for Biogen, Novartis, and Sanofi-Genzyme, and she has received research support from the Department of Defense, National MS Society, Guthy-Jackson Charitable Foundation, Novartis, Octave, Serono, and Verily. Dr. Zeydan had no disclosures to report.
SOURCE: Sotiropoulos MG et al. ACTRIMS Forum 2020. Abstract LB 317.
WEST PALM BEACH, FLA. – Failure to recover completely from early relapses in multiple sclerosis (MS) is significantly associated with higher long-term disability, according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Incomplete recovery thus should be given more consideration when evaluating research and clinical practice outcomes, the study investigators cautioned.
“We found that the recovery from early relapses is an important predictor of future disability,” first author Marinos G. Sotiropoulos, MD, of the department of neurology, Brigham and Women’s Hospital, Boston, said in an interview. “It should be incorporated in future predictive models of disease severity and clinical trials, [and] it could be useful in clinical decision making as well.”
Incomplete recovery from relapses is known to be linked to disability progression and to the likelihood of transitioning to secondary progressive MS. Research on its role in longer-term outcomes is lacking, however.
To investigate the effect of incomplete relapse recovery in the first 3 years of MS on rates of disability at 10 years, Dr. Sotiropoulos and colleagues evaluated data on 360 patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation in Multiple Sclerosis at Brigham and Women’s Hospital) study. CLIMB is a natural history study spanning 20 years, with more than 2,000 patients.
Patients were included if at least 8.5 years had passed since their first documented symptom, if they were at least 18 years at their first visit to the Partners MS Center, if that visit occurred within 1 year of their first symptom, and if they had a diagnosis of relapsing-remitting MS or secondary progressive MS.
Among the 308 patients included in the study, 74% were female and 89% were white, with a mean age at the first symptom of 35.9 years.
A total of 403 early attacks from those 308 patients were included in the study. Half of the attacks (50.4%) were followed by incomplete recovery after 6 months, defined specifically as an increase in the Expanded Disability Status Scale (EDSS) scores from baseline to at least 6 months after the onset of the attack.
As of their 10-year visit, 27.3% of patients had a normal examination, defined as EDSS 0, and 64.1% had no significant disability (EDSS less than 2). The mean EDSS at 10 years was 1.52.
Patients’ recovery index, defined as the percentage of early attacks that recovered completely, was significantly associated with 10-year EDSS scores (P less than .001).
Patient age at first symptom was also a significant predictor of 10-year disability (P less than .004). Factors that were significantly associated with incomplete relapse recovery were the duration of time from first symptom (P less than .001) and moderate severity of the relapse (P = .029).
With the type of drug treatment likely representing an important factor in whether a patient has incomplete relapse recovery, the issue should be the subject of further research, Dr. Sotiropoulos said.
“This is something that is important to look at because none of the clinical trials for the drugs we currently have looked at relapse recovery as an outcome,” he explained.
“There have been some post hoc analyses [that] have shown that some of the new medications can improve recovery from relapses, but there is a lot to look into now that we know relapse recovery is an important clinical parameter,” he said. “We have to factor in the treatment effect in preventing residual disability after relapses.”
The findings suggest that “patients with incomplete early recovery might be considered for highly effective disease-modifying therapy,” added senior author Tanuja Chitnis, MD, also of the department of neurology at Brigham and Women’s Hospital. “We are now analyzing the biological mechanisms associated with relapse recovery.”
The authors of a recent study that echoes the importance of relapse recovery call it “the forgotten variable in multiple sclerosis clinical trials.” In that study, the researchers found an increased likelihood of a benign disease course among patients who received immediate disease-modifying therapy (DMT) initiation after failing to have a good recovery from an initial relapse (Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17;7[2]).
“Some clinicians may choose to hold off DMTs because the patient may not have high disease activity levels,” Burcu Zeydan, MD, a coauthor of that study and an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic, Rochester, Minn., said in an interview.
“What these studies add is that, if a patient is a poor recoverer despite not having highly active disease, that patient should be considered for immediate treatment initiation,” she said. “Otherwise, there is the possibility of a next relapse, which may not happen often. But when it happens, it may lead to more residual deficit with additional disability burden.”
The CLIMB study received funding from Mallinckrodt and the National MS Society Nancy Davis Center Without Walls. Dr. Sotiropoulos has received research support from Mallinckrodt. Dr. Chitnis has served on advisory boards for Biogen, Novartis, and Sanofi-Genzyme, and she has received research support from the Department of Defense, National MS Society, Guthy-Jackson Charitable Foundation, Novartis, Octave, Serono, and Verily. Dr. Zeydan had no disclosures to report.
SOURCE: Sotiropoulos MG et al. ACTRIMS Forum 2020. Abstract LB 317.
WEST PALM BEACH, FLA. – Failure to recover completely from early relapses in multiple sclerosis (MS) is significantly associated with higher long-term disability, according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Incomplete recovery thus should be given more consideration when evaluating research and clinical practice outcomes, the study investigators cautioned.
“We found that the recovery from early relapses is an important predictor of future disability,” first author Marinos G. Sotiropoulos, MD, of the department of neurology, Brigham and Women’s Hospital, Boston, said in an interview. “It should be incorporated in future predictive models of disease severity and clinical trials, [and] it could be useful in clinical decision making as well.”
Incomplete recovery from relapses is known to be linked to disability progression and to the likelihood of transitioning to secondary progressive MS. Research on its role in longer-term outcomes is lacking, however.
To investigate the effect of incomplete relapse recovery in the first 3 years of MS on rates of disability at 10 years, Dr. Sotiropoulos and colleagues evaluated data on 360 patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation in Multiple Sclerosis at Brigham and Women’s Hospital) study. CLIMB is a natural history study spanning 20 years, with more than 2,000 patients.
Patients were included if at least 8.5 years had passed since their first documented symptom, if they were at least 18 years at their first visit to the Partners MS Center, if that visit occurred within 1 year of their first symptom, and if they had a diagnosis of relapsing-remitting MS or secondary progressive MS.
Among the 308 patients included in the study, 74% were female and 89% were white, with a mean age at the first symptom of 35.9 years.
A total of 403 early attacks from those 308 patients were included in the study. Half of the attacks (50.4%) were followed by incomplete recovery after 6 months, defined specifically as an increase in the Expanded Disability Status Scale (EDSS) scores from baseline to at least 6 months after the onset of the attack.
As of their 10-year visit, 27.3% of patients had a normal examination, defined as EDSS 0, and 64.1% had no significant disability (EDSS less than 2). The mean EDSS at 10 years was 1.52.
Patients’ recovery index, defined as the percentage of early attacks that recovered completely, was significantly associated with 10-year EDSS scores (P less than .001).
Patient age at first symptom was also a significant predictor of 10-year disability (P less than .004). Factors that were significantly associated with incomplete relapse recovery were the duration of time from first symptom (P less than .001) and moderate severity of the relapse (P = .029).
With the type of drug treatment likely representing an important factor in whether a patient has incomplete relapse recovery, the issue should be the subject of further research, Dr. Sotiropoulos said.
“This is something that is important to look at because none of the clinical trials for the drugs we currently have looked at relapse recovery as an outcome,” he explained.
“There have been some post hoc analyses [that] have shown that some of the new medications can improve recovery from relapses, but there is a lot to look into now that we know relapse recovery is an important clinical parameter,” he said. “We have to factor in the treatment effect in preventing residual disability after relapses.”
The findings suggest that “patients with incomplete early recovery might be considered for highly effective disease-modifying therapy,” added senior author Tanuja Chitnis, MD, also of the department of neurology at Brigham and Women’s Hospital. “We are now analyzing the biological mechanisms associated with relapse recovery.”
The authors of a recent study that echoes the importance of relapse recovery call it “the forgotten variable in multiple sclerosis clinical trials.” In that study, the researchers found an increased likelihood of a benign disease course among patients who received immediate disease-modifying therapy (DMT) initiation after failing to have a good recovery from an initial relapse (Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17;7[2]).
“Some clinicians may choose to hold off DMTs because the patient may not have high disease activity levels,” Burcu Zeydan, MD, a coauthor of that study and an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic, Rochester, Minn., said in an interview.
“What these studies add is that, if a patient is a poor recoverer despite not having highly active disease, that patient should be considered for immediate treatment initiation,” she said. “Otherwise, there is the possibility of a next relapse, which may not happen often. But when it happens, it may lead to more residual deficit with additional disability burden.”
The CLIMB study received funding from Mallinckrodt and the National MS Society Nancy Davis Center Without Walls. Dr. Sotiropoulos has received research support from Mallinckrodt. Dr. Chitnis has served on advisory boards for Biogen, Novartis, and Sanofi-Genzyme, and she has received research support from the Department of Defense, National MS Society, Guthy-Jackson Charitable Foundation, Novartis, Octave, Serono, and Verily. Dr. Zeydan had no disclosures to report.
SOURCE: Sotiropoulos MG et al. ACTRIMS Forum 2020. Abstract LB 317.
REPORTING FROM ACTRIMS FORUM 2020
Depression in MS predicted worsening of neurologic function
WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.
More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.
To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.
The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.
Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.
The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.
“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”
The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.
The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.
Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.
SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.
WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.
More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.
To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.
The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.
Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.
The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.
“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”
The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.
The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.
Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.
SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.
WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.
The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.
More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.
To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.
The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.
Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.
The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.
“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”
The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.
The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.
Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.
SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.
REPORTING FROM ACTRIMS Forum 2020
How often do neurologists escalate MS therapy after detecting MRI activity?
WEST PALM BEACH, FLA. – About a third of patients with multiple sclerosis (MS) switch to a more potent disease-modifying therapy (DMT) within 1 year of disease activity being detected on MRI, according to a study of prescribing practices. The number of T2 lesions on MRI may be associated with the likelihood of switching DMTs, said Ryan Canissario, MD, a neurology resident at University of Rochester (New York) Medical Center, and colleagues.
The researchers had hypothesized that “the majority of patients would undergo a change in DMT in response to MRI activity,” they said. Delays in follow-up or therapy start times may partly explain the relatively low rates of switching during the first few months. “We speculate that other reasons ... include clinician or patient risk tolerance, patient age, prior longstanding stability on existing therapy, recent therapy change prior to MRI, or high baseline DMT potency,” the researchers said. Future studies will try to clarify the findings and assess outcomes related to prescribing practices.
Preventing new lesions on MRI is a primary treatment target in MS. “Following this principle, change in [DMT] should be considered in the setting of MRI evidence of disease activity,” but prescribing practices have not been well characterized, Dr. Canissario and colleagues said.
To identify and characterize patients who underwent a DMT change after the detection of brain MRI disease activity, Dr. Canissario and colleagues analyzed data from more than 1,300 patients in MS PATHS (MS Partners Advancing Technology and Health Solutions), a research network of 10 health care institutions. The investigators presented their results at ACTRIMS Forum 2020, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
By consensus, the investigators classified DMTs as low potency (for example, interferons, immunoglobulin G, glatiramer acetate, and teriflunomide), medium potency (azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, methotrexate, and mycophenolate mofetil), or high potency (alemtuzumab, cyclophosphamide, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and rituximab).
The researchers reviewed available imaging data from Apr. 2015 to Aug. 2019 to identify patients with new T2 or gadolinium-enhancing lesions. They determined whether these patients had an escalation in DMT potency or a lateral switch at 3, 6, 9, and 12 months after a radiologist reviewed the MRI.
The number of patients with MRI evidence of disease activity and complete DMT data ranged from 1,364 at 3 months to 952 at 12 months. The proportion of patients who had an escalation in therapy was 17.4% at 3 months, 25.5% at 6 months, 30.4% at 9 months, and 34.3% at 12 months. The proportion with a lateral change was 2% at 3 months, 3.4% at 6 months, 4.3% at 9 months, and 6% at 12 months.
The percentage of patients with DMT escalation or lateral change at 9 months increased with an increasing number of new T2 lesions. About 27% of patients with one new lesion switched therapy, compared with 43.5% of those with more than three new lesions.
Dr. Canissario had no disclosures. Coauthors disclosed research support from and consulting for pharmaceutical companies. MS PATHS is funded by Biogen.
SOURCE: Canissario R et al. ACTRIMS Forum 2020. Abstract P112.
WEST PALM BEACH, FLA. – About a third of patients with multiple sclerosis (MS) switch to a more potent disease-modifying therapy (DMT) within 1 year of disease activity being detected on MRI, according to a study of prescribing practices. The number of T2 lesions on MRI may be associated with the likelihood of switching DMTs, said Ryan Canissario, MD, a neurology resident at University of Rochester (New York) Medical Center, and colleagues.
The researchers had hypothesized that “the majority of patients would undergo a change in DMT in response to MRI activity,” they said. Delays in follow-up or therapy start times may partly explain the relatively low rates of switching during the first few months. “We speculate that other reasons ... include clinician or patient risk tolerance, patient age, prior longstanding stability on existing therapy, recent therapy change prior to MRI, or high baseline DMT potency,” the researchers said. Future studies will try to clarify the findings and assess outcomes related to prescribing practices.
Preventing new lesions on MRI is a primary treatment target in MS. “Following this principle, change in [DMT] should be considered in the setting of MRI evidence of disease activity,” but prescribing practices have not been well characterized, Dr. Canissario and colleagues said.
To identify and characterize patients who underwent a DMT change after the detection of brain MRI disease activity, Dr. Canissario and colleagues analyzed data from more than 1,300 patients in MS PATHS (MS Partners Advancing Technology and Health Solutions), a research network of 10 health care institutions. The investigators presented their results at ACTRIMS Forum 2020, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
By consensus, the investigators classified DMTs as low potency (for example, interferons, immunoglobulin G, glatiramer acetate, and teriflunomide), medium potency (azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, methotrexate, and mycophenolate mofetil), or high potency (alemtuzumab, cyclophosphamide, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and rituximab).
The researchers reviewed available imaging data from Apr. 2015 to Aug. 2019 to identify patients with new T2 or gadolinium-enhancing lesions. They determined whether these patients had an escalation in DMT potency or a lateral switch at 3, 6, 9, and 12 months after a radiologist reviewed the MRI.
The number of patients with MRI evidence of disease activity and complete DMT data ranged from 1,364 at 3 months to 952 at 12 months. The proportion of patients who had an escalation in therapy was 17.4% at 3 months, 25.5% at 6 months, 30.4% at 9 months, and 34.3% at 12 months. The proportion with a lateral change was 2% at 3 months, 3.4% at 6 months, 4.3% at 9 months, and 6% at 12 months.
The percentage of patients with DMT escalation or lateral change at 9 months increased with an increasing number of new T2 lesions. About 27% of patients with one new lesion switched therapy, compared with 43.5% of those with more than three new lesions.
Dr. Canissario had no disclosures. Coauthors disclosed research support from and consulting for pharmaceutical companies. MS PATHS is funded by Biogen.
SOURCE: Canissario R et al. ACTRIMS Forum 2020. Abstract P112.
WEST PALM BEACH, FLA. – About a third of patients with multiple sclerosis (MS) switch to a more potent disease-modifying therapy (DMT) within 1 year of disease activity being detected on MRI, according to a study of prescribing practices. The number of T2 lesions on MRI may be associated with the likelihood of switching DMTs, said Ryan Canissario, MD, a neurology resident at University of Rochester (New York) Medical Center, and colleagues.
The researchers had hypothesized that “the majority of patients would undergo a change in DMT in response to MRI activity,” they said. Delays in follow-up or therapy start times may partly explain the relatively low rates of switching during the first few months. “We speculate that other reasons ... include clinician or patient risk tolerance, patient age, prior longstanding stability on existing therapy, recent therapy change prior to MRI, or high baseline DMT potency,” the researchers said. Future studies will try to clarify the findings and assess outcomes related to prescribing practices.
Preventing new lesions on MRI is a primary treatment target in MS. “Following this principle, change in [DMT] should be considered in the setting of MRI evidence of disease activity,” but prescribing practices have not been well characterized, Dr. Canissario and colleagues said.
To identify and characterize patients who underwent a DMT change after the detection of brain MRI disease activity, Dr. Canissario and colleagues analyzed data from more than 1,300 patients in MS PATHS (MS Partners Advancing Technology and Health Solutions), a research network of 10 health care institutions. The investigators presented their results at ACTRIMS Forum 2020, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
By consensus, the investigators classified DMTs as low potency (for example, interferons, immunoglobulin G, glatiramer acetate, and teriflunomide), medium potency (azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, methotrexate, and mycophenolate mofetil), or high potency (alemtuzumab, cyclophosphamide, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and rituximab).
The researchers reviewed available imaging data from Apr. 2015 to Aug. 2019 to identify patients with new T2 or gadolinium-enhancing lesions. They determined whether these patients had an escalation in DMT potency or a lateral switch at 3, 6, 9, and 12 months after a radiologist reviewed the MRI.
The number of patients with MRI evidence of disease activity and complete DMT data ranged from 1,364 at 3 months to 952 at 12 months. The proportion of patients who had an escalation in therapy was 17.4% at 3 months, 25.5% at 6 months, 30.4% at 9 months, and 34.3% at 12 months. The proportion with a lateral change was 2% at 3 months, 3.4% at 6 months, 4.3% at 9 months, and 6% at 12 months.
The percentage of patients with DMT escalation or lateral change at 9 months increased with an increasing number of new T2 lesions. About 27% of patients with one new lesion switched therapy, compared with 43.5% of those with more than three new lesions.
Dr. Canissario had no disclosures. Coauthors disclosed research support from and consulting for pharmaceutical companies. MS PATHS is funded by Biogen.
SOURCE: Canissario R et al. ACTRIMS Forum 2020. Abstract P112.
REPORTING FROM ACTRIMS FORUM 2020
Incidence of cardiovascular events is doubled in patients with MS
WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.
Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.
The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.
A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.
Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.
The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.
The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.
The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).
“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).
The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.
The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.
SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.
WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.
Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.
The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.
A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.
Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.
The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.
The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.
The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).
“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).
The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.
The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.
SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.
WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.
Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.
The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.
A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.
Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.
The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.
The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.
The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).
“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).
The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.
The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.
SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.
REPORTING FROM ACTRIMS FORUM 2020
Functional connectivity model identifies MS impairment
WEST PALM BEACH, FLA. – A machine learning model that combines data on the brain’s functional connectivity with clinical information such as age, sex and disease duration shows the potential to provide an accurate assessment of clinical impairment in patients with multiple sclerosis (MS).
“This is the first study to show that dynamic functional connectivity is useful to identify the impairment level in MS, and can be used for personalized treatment by clinicians,” first author Ceren Tozlu, PhD, of Weill Cornell Medicine, New York, said in an interview.
“We found out that structural connectivity is the most important feature that distinguishes MS patients from healthy controls, while dynamic functional connectivity was more discriminative compared to the static functional connectivity in MS patient classification regarding their impairment level.”
The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Statistical assessment of the clinical impairment of MS using MRI is hindered by a relatively weak correlation between the impairment and disease burden, such as lesion load.
However, the brain’s functional connectivity network, which is indicative of the disruption of the transmission of signals of gray matter regions, could provide a deeper understanding of connectome-level mechanisms that underlie variability in MS-related impairments, Dr. Tozlu and colleagues say.
With no previous study pulling together multimodal imaging data including static and dynamic functional connectivity to classify MS patients with a clinically significant impairment versus non–clinically significant impairment, Dr. Tozlu and the team sought to build a machine-learning–based model to do so.
For the study, they enrolled 79 patients with MS, including 42 with Expanded Disability Status scores of 2 or higher, representing clinically significant impairment at baseline.
The patients, who had a mean age of 45 years, were 66% female and had a mean disease duration of 12.48 years. The ensemble model that was used incorporated functional connectivity and a clinical dataset of age, sex, and disease duration. Functional connectivity was measured by evaluating blood oxygen level dependent (BOLD) signal activity between 86 FreeSurfer-based gray matter regions.
“Functional connectivity is a statistical correlation (Pearson’s correlation coefficient) between two time series of BOLD signals measured on two distinct region of interest of the brain during MRI scan,” Dr. Tozlu explained. “In our study, BOLD time series were measured using resting-state functional MRI technique that last 7 minutes.”
The ensemble model was able to classify low-adapting MS patients with an area under ROC curve (AUC) of 0.638 and a balanced accuracy of 0.659. The model performed well in accurately classifying the MS patients with clinically significant impairment with a sensitivity of 0.719.
“The models in which we applied functional and structural connectivity showed a high performance in classifying MS patients regarding their impairment level,” Dr. Tozlu said.
She noted that “these models may be extended to predict change in impairment level in a longitudinal study, for instance, identifying MS patients who may have a clinically significant impairment.”
In further evaluating which particular functional connections were most related to MS disease activity, Dr. Tozlu and colleagues found the most discriminative areas were between the right superior parietal and right inferior temporal, between right lateral occipital and left pericalcarine, and between right pericalcarine and right side of frontal pole.
If further validated, the approach could have important, broader clinical implications, Dr. Tozlu said.
“If the validation of these models on a larger dataset is successful, this model may be used to decide for personalized treatment,” Dr. Tozlu added. “The model could offer guidance in providing more powerful treatment for MS patients who may have a clinically significant impairment and less powerful treatment for MS patients who may not have a clinically significant impairment in order to avoid the side effects of treatments.
“Therefore, we believe that dynamics in functional connectivity should be taken into account in the next studies in MS.”
In commenting on the research, Eric Klawiter, MD, associate professor of neurology, Harvard Medical School and associate neurologist at Massachusetts General Hospital, both in Boston, said the findings offer valuable insights in the use of machine learning and MS imaging.
“This research shows very nicely the power of machine learning and connectivity techniques to differentiate MS phenotypes based on disability level,” he said in an interview.
“The future direction of this work is to develop predictive markers for disability progression and this would have significant impact in how we evaluate newly diagnosed patients and counsel their treatment decisions.”
Dr. Tozlu and Dr. Klawiter had no disclosures to report.
SOURCE: Tozlu C et al. ACTRIMS Forum 2020. Abstract P025.
WEST PALM BEACH, FLA. – A machine learning model that combines data on the brain’s functional connectivity with clinical information such as age, sex and disease duration shows the potential to provide an accurate assessment of clinical impairment in patients with multiple sclerosis (MS).
“This is the first study to show that dynamic functional connectivity is useful to identify the impairment level in MS, and can be used for personalized treatment by clinicians,” first author Ceren Tozlu, PhD, of Weill Cornell Medicine, New York, said in an interview.
“We found out that structural connectivity is the most important feature that distinguishes MS patients from healthy controls, while dynamic functional connectivity was more discriminative compared to the static functional connectivity in MS patient classification regarding their impairment level.”
The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Statistical assessment of the clinical impairment of MS using MRI is hindered by a relatively weak correlation between the impairment and disease burden, such as lesion load.
However, the brain’s functional connectivity network, which is indicative of the disruption of the transmission of signals of gray matter regions, could provide a deeper understanding of connectome-level mechanisms that underlie variability in MS-related impairments, Dr. Tozlu and colleagues say.
With no previous study pulling together multimodal imaging data including static and dynamic functional connectivity to classify MS patients with a clinically significant impairment versus non–clinically significant impairment, Dr. Tozlu and the team sought to build a machine-learning–based model to do so.
For the study, they enrolled 79 patients with MS, including 42 with Expanded Disability Status scores of 2 or higher, representing clinically significant impairment at baseline.
The patients, who had a mean age of 45 years, were 66% female and had a mean disease duration of 12.48 years. The ensemble model that was used incorporated functional connectivity and a clinical dataset of age, sex, and disease duration. Functional connectivity was measured by evaluating blood oxygen level dependent (BOLD) signal activity between 86 FreeSurfer-based gray matter regions.
“Functional connectivity is a statistical correlation (Pearson’s correlation coefficient) between two time series of BOLD signals measured on two distinct region of interest of the brain during MRI scan,” Dr. Tozlu explained. “In our study, BOLD time series were measured using resting-state functional MRI technique that last 7 minutes.”
The ensemble model was able to classify low-adapting MS patients with an area under ROC curve (AUC) of 0.638 and a balanced accuracy of 0.659. The model performed well in accurately classifying the MS patients with clinically significant impairment with a sensitivity of 0.719.
“The models in which we applied functional and structural connectivity showed a high performance in classifying MS patients regarding their impairment level,” Dr. Tozlu said.
She noted that “these models may be extended to predict change in impairment level in a longitudinal study, for instance, identifying MS patients who may have a clinically significant impairment.”
In further evaluating which particular functional connections were most related to MS disease activity, Dr. Tozlu and colleagues found the most discriminative areas were between the right superior parietal and right inferior temporal, between right lateral occipital and left pericalcarine, and between right pericalcarine and right side of frontal pole.
If further validated, the approach could have important, broader clinical implications, Dr. Tozlu said.
“If the validation of these models on a larger dataset is successful, this model may be used to decide for personalized treatment,” Dr. Tozlu added. “The model could offer guidance in providing more powerful treatment for MS patients who may have a clinically significant impairment and less powerful treatment for MS patients who may not have a clinically significant impairment in order to avoid the side effects of treatments.
“Therefore, we believe that dynamics in functional connectivity should be taken into account in the next studies in MS.”
In commenting on the research, Eric Klawiter, MD, associate professor of neurology, Harvard Medical School and associate neurologist at Massachusetts General Hospital, both in Boston, said the findings offer valuable insights in the use of machine learning and MS imaging.
“This research shows very nicely the power of machine learning and connectivity techniques to differentiate MS phenotypes based on disability level,” he said in an interview.
“The future direction of this work is to develop predictive markers for disability progression and this would have significant impact in how we evaluate newly diagnosed patients and counsel their treatment decisions.”
Dr. Tozlu and Dr. Klawiter had no disclosures to report.
SOURCE: Tozlu C et al. ACTRIMS Forum 2020. Abstract P025.
WEST PALM BEACH, FLA. – A machine learning model that combines data on the brain’s functional connectivity with clinical information such as age, sex and disease duration shows the potential to provide an accurate assessment of clinical impairment in patients with multiple sclerosis (MS).
“This is the first study to show that dynamic functional connectivity is useful to identify the impairment level in MS, and can be used for personalized treatment by clinicians,” first author Ceren Tozlu, PhD, of Weill Cornell Medicine, New York, said in an interview.
“We found out that structural connectivity is the most important feature that distinguishes MS patients from healthy controls, while dynamic functional connectivity was more discriminative compared to the static functional connectivity in MS patient classification regarding their impairment level.”
The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Statistical assessment of the clinical impairment of MS using MRI is hindered by a relatively weak correlation between the impairment and disease burden, such as lesion load.
However, the brain’s functional connectivity network, which is indicative of the disruption of the transmission of signals of gray matter regions, could provide a deeper understanding of connectome-level mechanisms that underlie variability in MS-related impairments, Dr. Tozlu and colleagues say.
With no previous study pulling together multimodal imaging data including static and dynamic functional connectivity to classify MS patients with a clinically significant impairment versus non–clinically significant impairment, Dr. Tozlu and the team sought to build a machine-learning–based model to do so.
For the study, they enrolled 79 patients with MS, including 42 with Expanded Disability Status scores of 2 or higher, representing clinically significant impairment at baseline.
The patients, who had a mean age of 45 years, were 66% female and had a mean disease duration of 12.48 years. The ensemble model that was used incorporated functional connectivity and a clinical dataset of age, sex, and disease duration. Functional connectivity was measured by evaluating blood oxygen level dependent (BOLD) signal activity between 86 FreeSurfer-based gray matter regions.
“Functional connectivity is a statistical correlation (Pearson’s correlation coefficient) between two time series of BOLD signals measured on two distinct region of interest of the brain during MRI scan,” Dr. Tozlu explained. “In our study, BOLD time series were measured using resting-state functional MRI technique that last 7 minutes.”
The ensemble model was able to classify low-adapting MS patients with an area under ROC curve (AUC) of 0.638 and a balanced accuracy of 0.659. The model performed well in accurately classifying the MS patients with clinically significant impairment with a sensitivity of 0.719.
“The models in which we applied functional and structural connectivity showed a high performance in classifying MS patients regarding their impairment level,” Dr. Tozlu said.
She noted that “these models may be extended to predict change in impairment level in a longitudinal study, for instance, identifying MS patients who may have a clinically significant impairment.”
In further evaluating which particular functional connections were most related to MS disease activity, Dr. Tozlu and colleagues found the most discriminative areas were between the right superior parietal and right inferior temporal, between right lateral occipital and left pericalcarine, and between right pericalcarine and right side of frontal pole.
If further validated, the approach could have important, broader clinical implications, Dr. Tozlu said.
“If the validation of these models on a larger dataset is successful, this model may be used to decide for personalized treatment,” Dr. Tozlu added. “The model could offer guidance in providing more powerful treatment for MS patients who may have a clinically significant impairment and less powerful treatment for MS patients who may not have a clinically significant impairment in order to avoid the side effects of treatments.
“Therefore, we believe that dynamics in functional connectivity should be taken into account in the next studies in MS.”
In commenting on the research, Eric Klawiter, MD, associate professor of neurology, Harvard Medical School and associate neurologist at Massachusetts General Hospital, both in Boston, said the findings offer valuable insights in the use of machine learning and MS imaging.
“This research shows very nicely the power of machine learning and connectivity techniques to differentiate MS phenotypes based on disability level,” he said in an interview.
“The future direction of this work is to develop predictive markers for disability progression and this would have significant impact in how we evaluate newly diagnosed patients and counsel their treatment decisions.”
Dr. Tozlu and Dr. Klawiter had no disclosures to report.
SOURCE: Tozlu C et al. ACTRIMS Forum 2020. Abstract P025.
REPORTING FROM ACTRIMS FORUM 2020
Key clinical point:
Major finding: The model classified low-adapting MS patients with an ROC curve (AUC) of 0.638 and a balanced accuracy of 0.659.
Study details: Modeling study based on 79 patients with MS, including low adapters.
Disclosures: Dr. Tozlu and Dr. Klawiter had no disclosures to report.
Source: Tozlu C et al. ACTRIMS Forum 2020. Abstract P025.
Inebilizumab benefits patients with NMOSD
WEST PALM BEACH, FLA. – Compared with placebo, inebilizumab reduces the risk of attacks, the risk of disability worsening, the number of hospitalizations, and the number of new MRI lesions in patients with neuromyelitis optica spectrum disorder (NMOSD), according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The drug’s efficacy was sustained for one year in the study, and the treatment had an acceptable safety profile.
“Multiple lines of evidence suggest that NMO is predominantly a B-cell–mediated disorder,” said Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences. Inebilizumab depletes B cells and reduces inflammatory disease activity in NMO potentially by altering immune networks that are dependent on B cells for cytokine production or antigen presentation.” Inebilizumab is an anti-CD19 monoclonal antibody.
Dr. Cree and colleagues conducted a randomized, controlled trial called N-MOmentum to characterize the long-term efficacy and safety of inebilizumab in patients with NMOSD. The investigators randomized patients with NMOSD to inebilizumab or placebo monotherapy in a 3:1 ratio for 6.5 months. The study’s primary outcome was the time to the first adjudicated attack. Patients who had an adjudicated attack or completed the trial could receive inebilizumab in an ongoing open-label extension.
The study was conducted at 99 sites in 25 countries. In all, 230 patients were randomized and dosed (174 received inebilizumab, and 56 received placebo). About 91% of the population was aquaporin-4-IgG–positive (AQP4-IgG+), and 91% was female. The population’s mean age at baseline was 43 years. The population’s median baseline Expanded Disability Status Scale score was approximately 3.5, and the range was from 0 to 8.0. Approximately 50% of participants were white, 20% were Asian, and 9% were of African descent. “The demographic profile is similar to that of many published studies,” said Dr. Cree.
Because of clear evidence of efficacy, the independent data monitoring committee recommended that the study be stopped early. In the randomized, controlled trial, inebilizumab reduced the risk of attack by 77.3% among AQP4-IgG+ patients and by 72.8% in the total population. The number needed to treat for 6.5 months to prevent one attack was 3.2 for the AQP4-IgG+ group and 3.7 for the total population.
Furthermore, inebilizumab significantly reduced the risk of worsening disability, the number of new MRI lesions, and NMOSD-related hospitalizations. After 1 year on inebilizumab, 85% of patients were free of an NMOSD attack. In safety analyses that combined data from the randomized, controlled trial and interim data from the open-label extension, the mean duration of inebilizumab treatment was 1.5 years.
“The rapid effect of inebilizumab on attack prevention is not mediated by decreasing AQP4-IgG, although it is possible that long-term inebilizumab treatment might eventually reduce AQP4-IgG production,” said Dr. Cree.
The most common adverse events (AEs) were urinary tract infection (UTI, 19.6%), nasopharyngitis (12.9%), and infusion-related reactions (IRRs, 11.6%). IRRs were most common with the first infusion. The proportion of inebilizumab-treated patients with IgG levels below the lower limit of normal was 7.5% at 1 year and 13.4% at 2 years. Serious AEs occurred in 12% of patients, and UTI was the most common (2.2%). Two patients died in the open-label extension; one death resulted from NMOSD, and one from new presumed inflammatory brain lesions of undetermined etiology.
“The open-label results show a striking durability of treatment effect,” said Dr. Cree. “Most of the attacks that occurred during the open-label extension occurred early on, suggesting that the risk of attack decreases with duration of B-cell depletion. The open-label study also is important for assessing the longer-term AE profile of inebilizumab treatment. One potentially important observation from the open-label extension is that the extent of B-cell depletion correlates with reduced attack risk. Approximately 95% of participants with deep B-cell depletion were free of attacks. Participants who either incompletely depleted B cells or who began to reconstitute B cells more rapidly were at increased risk of attack. Therefore, by monitoring B-cell counts in inebilizumab-treated patients, it may be possible to further reduce the risk of attack in patients who partially deplete, or replete B cells early, with an extra inebilizumab treatment.”
Viela Bio, which is developing inebilizumab, and MedImmune sponsored the study. Dr. Cree has received compensation for consulting services that he provided to Alexion, Atara, Biogen, EMD Serono, Novartis, and TG Therapeutics.
SOURCE: Cree BA et al. ACTRIMS 2020. Abstract P207.
WEST PALM BEACH, FLA. – Compared with placebo, inebilizumab reduces the risk of attacks, the risk of disability worsening, the number of hospitalizations, and the number of new MRI lesions in patients with neuromyelitis optica spectrum disorder (NMOSD), according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The drug’s efficacy was sustained for one year in the study, and the treatment had an acceptable safety profile.
“Multiple lines of evidence suggest that NMO is predominantly a B-cell–mediated disorder,” said Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences. Inebilizumab depletes B cells and reduces inflammatory disease activity in NMO potentially by altering immune networks that are dependent on B cells for cytokine production or antigen presentation.” Inebilizumab is an anti-CD19 monoclonal antibody.
Dr. Cree and colleagues conducted a randomized, controlled trial called N-MOmentum to characterize the long-term efficacy and safety of inebilizumab in patients with NMOSD. The investigators randomized patients with NMOSD to inebilizumab or placebo monotherapy in a 3:1 ratio for 6.5 months. The study’s primary outcome was the time to the first adjudicated attack. Patients who had an adjudicated attack or completed the trial could receive inebilizumab in an ongoing open-label extension.
The study was conducted at 99 sites in 25 countries. In all, 230 patients were randomized and dosed (174 received inebilizumab, and 56 received placebo). About 91% of the population was aquaporin-4-IgG–positive (AQP4-IgG+), and 91% was female. The population’s mean age at baseline was 43 years. The population’s median baseline Expanded Disability Status Scale score was approximately 3.5, and the range was from 0 to 8.0. Approximately 50% of participants were white, 20% were Asian, and 9% were of African descent. “The demographic profile is similar to that of many published studies,” said Dr. Cree.
Because of clear evidence of efficacy, the independent data monitoring committee recommended that the study be stopped early. In the randomized, controlled trial, inebilizumab reduced the risk of attack by 77.3% among AQP4-IgG+ patients and by 72.8% in the total population. The number needed to treat for 6.5 months to prevent one attack was 3.2 for the AQP4-IgG+ group and 3.7 for the total population.
Furthermore, inebilizumab significantly reduced the risk of worsening disability, the number of new MRI lesions, and NMOSD-related hospitalizations. After 1 year on inebilizumab, 85% of patients were free of an NMOSD attack. In safety analyses that combined data from the randomized, controlled trial and interim data from the open-label extension, the mean duration of inebilizumab treatment was 1.5 years.
“The rapid effect of inebilizumab on attack prevention is not mediated by decreasing AQP4-IgG, although it is possible that long-term inebilizumab treatment might eventually reduce AQP4-IgG production,” said Dr. Cree.
The most common adverse events (AEs) were urinary tract infection (UTI, 19.6%), nasopharyngitis (12.9%), and infusion-related reactions (IRRs, 11.6%). IRRs were most common with the first infusion. The proportion of inebilizumab-treated patients with IgG levels below the lower limit of normal was 7.5% at 1 year and 13.4% at 2 years. Serious AEs occurred in 12% of patients, and UTI was the most common (2.2%). Two patients died in the open-label extension; one death resulted from NMOSD, and one from new presumed inflammatory brain lesions of undetermined etiology.
“The open-label results show a striking durability of treatment effect,” said Dr. Cree. “Most of the attacks that occurred during the open-label extension occurred early on, suggesting that the risk of attack decreases with duration of B-cell depletion. The open-label study also is important for assessing the longer-term AE profile of inebilizumab treatment. One potentially important observation from the open-label extension is that the extent of B-cell depletion correlates with reduced attack risk. Approximately 95% of participants with deep B-cell depletion were free of attacks. Participants who either incompletely depleted B cells or who began to reconstitute B cells more rapidly were at increased risk of attack. Therefore, by monitoring B-cell counts in inebilizumab-treated patients, it may be possible to further reduce the risk of attack in patients who partially deplete, or replete B cells early, with an extra inebilizumab treatment.”
Viela Bio, which is developing inebilizumab, and MedImmune sponsored the study. Dr. Cree has received compensation for consulting services that he provided to Alexion, Atara, Biogen, EMD Serono, Novartis, and TG Therapeutics.
SOURCE: Cree BA et al. ACTRIMS 2020. Abstract P207.
WEST PALM BEACH, FLA. – Compared with placebo, inebilizumab reduces the risk of attacks, the risk of disability worsening, the number of hospitalizations, and the number of new MRI lesions in patients with neuromyelitis optica spectrum disorder (NMOSD), according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The drug’s efficacy was sustained for one year in the study, and the treatment had an acceptable safety profile.
“Multiple lines of evidence suggest that NMO is predominantly a B-cell–mediated disorder,” said Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences. Inebilizumab depletes B cells and reduces inflammatory disease activity in NMO potentially by altering immune networks that are dependent on B cells for cytokine production or antigen presentation.” Inebilizumab is an anti-CD19 monoclonal antibody.
Dr. Cree and colleagues conducted a randomized, controlled trial called N-MOmentum to characterize the long-term efficacy and safety of inebilizumab in patients with NMOSD. The investigators randomized patients with NMOSD to inebilizumab or placebo monotherapy in a 3:1 ratio for 6.5 months. The study’s primary outcome was the time to the first adjudicated attack. Patients who had an adjudicated attack or completed the trial could receive inebilizumab in an ongoing open-label extension.
The study was conducted at 99 sites in 25 countries. In all, 230 patients were randomized and dosed (174 received inebilizumab, and 56 received placebo). About 91% of the population was aquaporin-4-IgG–positive (AQP4-IgG+), and 91% was female. The population’s mean age at baseline was 43 years. The population’s median baseline Expanded Disability Status Scale score was approximately 3.5, and the range was from 0 to 8.0. Approximately 50% of participants were white, 20% were Asian, and 9% were of African descent. “The demographic profile is similar to that of many published studies,” said Dr. Cree.
Because of clear evidence of efficacy, the independent data monitoring committee recommended that the study be stopped early. In the randomized, controlled trial, inebilizumab reduced the risk of attack by 77.3% among AQP4-IgG+ patients and by 72.8% in the total population. The number needed to treat for 6.5 months to prevent one attack was 3.2 for the AQP4-IgG+ group and 3.7 for the total population.
Furthermore, inebilizumab significantly reduced the risk of worsening disability, the number of new MRI lesions, and NMOSD-related hospitalizations. After 1 year on inebilizumab, 85% of patients were free of an NMOSD attack. In safety analyses that combined data from the randomized, controlled trial and interim data from the open-label extension, the mean duration of inebilizumab treatment was 1.5 years.
“The rapid effect of inebilizumab on attack prevention is not mediated by decreasing AQP4-IgG, although it is possible that long-term inebilizumab treatment might eventually reduce AQP4-IgG production,” said Dr. Cree.
The most common adverse events (AEs) were urinary tract infection (UTI, 19.6%), nasopharyngitis (12.9%), and infusion-related reactions (IRRs, 11.6%). IRRs were most common with the first infusion. The proportion of inebilizumab-treated patients with IgG levels below the lower limit of normal was 7.5% at 1 year and 13.4% at 2 years. Serious AEs occurred in 12% of patients, and UTI was the most common (2.2%). Two patients died in the open-label extension; one death resulted from NMOSD, and one from new presumed inflammatory brain lesions of undetermined etiology.
“The open-label results show a striking durability of treatment effect,” said Dr. Cree. “Most of the attacks that occurred during the open-label extension occurred early on, suggesting that the risk of attack decreases with duration of B-cell depletion. The open-label study also is important for assessing the longer-term AE profile of inebilizumab treatment. One potentially important observation from the open-label extension is that the extent of B-cell depletion correlates with reduced attack risk. Approximately 95% of participants with deep B-cell depletion were free of attacks. Participants who either incompletely depleted B cells or who began to reconstitute B cells more rapidly were at increased risk of attack. Therefore, by monitoring B-cell counts in inebilizumab-treated patients, it may be possible to further reduce the risk of attack in patients who partially deplete, or replete B cells early, with an extra inebilizumab treatment.”
Viela Bio, which is developing inebilizumab, and MedImmune sponsored the study. Dr. Cree has received compensation for consulting services that he provided to Alexion, Atara, Biogen, EMD Serono, Novartis, and TG Therapeutics.
SOURCE: Cree BA et al. ACTRIMS 2020. Abstract P207.
REPORTING FROM ACTRIMS FORUM 2020
Eculizumab reduces relapse-related hospitalizations in patients with NMOSD
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that eculizumab may have a favorable effect on health-resource utilization.
Many patients with NMOSD, a rare autoimmune inflammatory disease, have relapses that result in hospitalization. Eculizumab (Soliris)is a humanized monoclonal antibody that inhibits the terminal complement protein C5. In the randomized, double-blind, placebo-controlled PREVENT study, Dean M. Wingerchuk, MD, chair of neurology at Mayo Clinic in Phoenix, , and colleagues found that eculizumab was associated with a 94% reduction in the risk of relapse, compared with placebo, in AQP4-IgG-positive patients with NMOSD.
In a new analysis of the PREVENT data, the investigators sought to evaluate rates of relapse-related hospitalization and associated treatment among study participants. The researchers chose time to first adjudicated relapse as their primary endpoint.
In the PREVENT study, Dr. Wingerchuk and colleagues randomized patients with AQP4-IgG-positive NMOSD to eculizumab (1,200 mg/2 weeks) or placebo. The annualized relapse-related hospitalization and treatment rates were calculated as the number of relapses requiring hospitalization or treatment divided by the total number of patient-years during the study.
Approximately 91% of participants were female. Mean age at initial clinical presentation was about 37 years. Participants’ median Expanded Disability Status Scale score at baseline was 4, and their mean annualized relapse rate in the 24 months before screening was 2. In all, 96 patients received eculizumab, and 47 received placebo. The median length of exposure to treatment was 89.4 weeks in the eculizumab group and 41.3 weeks among controls.
The rate of adverse events requiring hospitalization was 29% in the eculizumab group and 53% in the placebo group. The most common events requiring hospitalization were physician-determined relapses. Infections were the next most common events requiring hospitalization.
The overall annualized hospitalization rate was 0.26 in the eculizumab group and 0.78 in the placebo group. The difference between groups was statistically significant. In addition, the annualized relapse-related hospitalization rate was lower in the eculizumab group than in the placebo group (0.04 vs. 0.31, respectively).
The annualized relapse-related use of intravenous methylprednisolone for the eculizumab and placebo groups were 0.07 and 0.42, respectively; for use of plasma exchange, 0.02 and 0.19; and for use of high-dose oral corticosteroids, 0.04 and 0.11. The differences between groups in use of intravenous methylprednisolone and plasma exchange were statistically significant.
Alexion Pharmaceuticals, which markets eculizumab, sponsored the study. Dr. Wingerchuk received grants from Alexion during the study. He also received personal fees from Biogen, BrainStorm Therapeutics, Celgene, MedImmune, Novartis, and ONO Pharmaceutical.
SOURCE: Kim H et al. ACTRIMS 2020. Abstract P197.
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that eculizumab may have a favorable effect on health-resource utilization.
Many patients with NMOSD, a rare autoimmune inflammatory disease, have relapses that result in hospitalization. Eculizumab (Soliris)is a humanized monoclonal antibody that inhibits the terminal complement protein C5. In the randomized, double-blind, placebo-controlled PREVENT study, Dean M. Wingerchuk, MD, chair of neurology at Mayo Clinic in Phoenix, , and colleagues found that eculizumab was associated with a 94% reduction in the risk of relapse, compared with placebo, in AQP4-IgG-positive patients with NMOSD.
In a new analysis of the PREVENT data, the investigators sought to evaluate rates of relapse-related hospitalization and associated treatment among study participants. The researchers chose time to first adjudicated relapse as their primary endpoint.
In the PREVENT study, Dr. Wingerchuk and colleagues randomized patients with AQP4-IgG-positive NMOSD to eculizumab (1,200 mg/2 weeks) or placebo. The annualized relapse-related hospitalization and treatment rates were calculated as the number of relapses requiring hospitalization or treatment divided by the total number of patient-years during the study.
Approximately 91% of participants were female. Mean age at initial clinical presentation was about 37 years. Participants’ median Expanded Disability Status Scale score at baseline was 4, and their mean annualized relapse rate in the 24 months before screening was 2. In all, 96 patients received eculizumab, and 47 received placebo. The median length of exposure to treatment was 89.4 weeks in the eculizumab group and 41.3 weeks among controls.
The rate of adverse events requiring hospitalization was 29% in the eculizumab group and 53% in the placebo group. The most common events requiring hospitalization were physician-determined relapses. Infections were the next most common events requiring hospitalization.
The overall annualized hospitalization rate was 0.26 in the eculizumab group and 0.78 in the placebo group. The difference between groups was statistically significant. In addition, the annualized relapse-related hospitalization rate was lower in the eculizumab group than in the placebo group (0.04 vs. 0.31, respectively).
The annualized relapse-related use of intravenous methylprednisolone for the eculizumab and placebo groups were 0.07 and 0.42, respectively; for use of plasma exchange, 0.02 and 0.19; and for use of high-dose oral corticosteroids, 0.04 and 0.11. The differences between groups in use of intravenous methylprednisolone and plasma exchange were statistically significant.
Alexion Pharmaceuticals, which markets eculizumab, sponsored the study. Dr. Wingerchuk received grants from Alexion during the study. He also received personal fees from Biogen, BrainStorm Therapeutics, Celgene, MedImmune, Novartis, and ONO Pharmaceutical.
SOURCE: Kim H et al. ACTRIMS 2020. Abstract P197.
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that eculizumab may have a favorable effect on health-resource utilization.
Many patients with NMOSD, a rare autoimmune inflammatory disease, have relapses that result in hospitalization. Eculizumab (Soliris)is a humanized monoclonal antibody that inhibits the terminal complement protein C5. In the randomized, double-blind, placebo-controlled PREVENT study, Dean M. Wingerchuk, MD, chair of neurology at Mayo Clinic in Phoenix, , and colleagues found that eculizumab was associated with a 94% reduction in the risk of relapse, compared with placebo, in AQP4-IgG-positive patients with NMOSD.
In a new analysis of the PREVENT data, the investigators sought to evaluate rates of relapse-related hospitalization and associated treatment among study participants. The researchers chose time to first adjudicated relapse as their primary endpoint.
In the PREVENT study, Dr. Wingerchuk and colleagues randomized patients with AQP4-IgG-positive NMOSD to eculizumab (1,200 mg/2 weeks) or placebo. The annualized relapse-related hospitalization and treatment rates were calculated as the number of relapses requiring hospitalization or treatment divided by the total number of patient-years during the study.
Approximately 91% of participants were female. Mean age at initial clinical presentation was about 37 years. Participants’ median Expanded Disability Status Scale score at baseline was 4, and their mean annualized relapse rate in the 24 months before screening was 2. In all, 96 patients received eculizumab, and 47 received placebo. The median length of exposure to treatment was 89.4 weeks in the eculizumab group and 41.3 weeks among controls.
The rate of adverse events requiring hospitalization was 29% in the eculizumab group and 53% in the placebo group. The most common events requiring hospitalization were physician-determined relapses. Infections were the next most common events requiring hospitalization.
The overall annualized hospitalization rate was 0.26 in the eculizumab group and 0.78 in the placebo group. The difference between groups was statistically significant. In addition, the annualized relapse-related hospitalization rate was lower in the eculizumab group than in the placebo group (0.04 vs. 0.31, respectively).
The annualized relapse-related use of intravenous methylprednisolone for the eculizumab and placebo groups were 0.07 and 0.42, respectively; for use of plasma exchange, 0.02 and 0.19; and for use of high-dose oral corticosteroids, 0.04 and 0.11. The differences between groups in use of intravenous methylprednisolone and plasma exchange were statistically significant.
Alexion Pharmaceuticals, which markets eculizumab, sponsored the study. Dr. Wingerchuk received grants from Alexion during the study. He also received personal fees from Biogen, BrainStorm Therapeutics, Celgene, MedImmune, Novartis, and ONO Pharmaceutical.
SOURCE: Kim H et al. ACTRIMS 2020. Abstract P197.
REPORTING FROM ACTRIMS FORUM 2020