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Elevated D-dimer after infusion of alemtuzumab in patients with MS
Key clinical point: Alemtuzumab infusion in patients with multiple sclerosis (MS) is associated with the elevation of D-dimer level and the prolongation of prothrombin time (PT).
Major finding: Alemtuzumab infusion resulted in a significant elevation in D-dimer levels within the patient group (before vs after infusion, P = .00001) and also compared with control individuals (P = .00001). PT was also prolonged in patients receiving alemtuzumab post-infusion compared with the pre-infusion values (P = .00001).
Study details: In this study, coagulation parameters were analyzed in 13 patients with MS treated with alemtuzumab and 13 control individuals.
Disclosures: The study was supported by the MH CZ-DRO, Motol University Hospital, Prague, Czech Republic. Jana Libertinova, Eva Meluzinova, Eva Nema, Petra Rockova, Martin Elisak, Marko Petrzalka, and Hana Mojzisova reported receiving compensation for travel and/or speaker honoraria and consultant fees from multiple pharmaceutical companies. The remaining authors declared no conflict of interest.
Citation: Libertinova J et al. Mult Scler. 2020 Feb 20. doi: 10.1177/1352458520904277.
Key clinical point: Alemtuzumab infusion in patients with multiple sclerosis (MS) is associated with the elevation of D-dimer level and the prolongation of prothrombin time (PT).
Major finding: Alemtuzumab infusion resulted in a significant elevation in D-dimer levels within the patient group (before vs after infusion, P = .00001) and also compared with control individuals (P = .00001). PT was also prolonged in patients receiving alemtuzumab post-infusion compared with the pre-infusion values (P = .00001).
Study details: In this study, coagulation parameters were analyzed in 13 patients with MS treated with alemtuzumab and 13 control individuals.
Disclosures: The study was supported by the MH CZ-DRO, Motol University Hospital, Prague, Czech Republic. Jana Libertinova, Eva Meluzinova, Eva Nema, Petra Rockova, Martin Elisak, Marko Petrzalka, and Hana Mojzisova reported receiving compensation for travel and/or speaker honoraria and consultant fees from multiple pharmaceutical companies. The remaining authors declared no conflict of interest.
Citation: Libertinova J et al. Mult Scler. 2020 Feb 20. doi: 10.1177/1352458520904277.
Key clinical point: Alemtuzumab infusion in patients with multiple sclerosis (MS) is associated with the elevation of D-dimer level and the prolongation of prothrombin time (PT).
Major finding: Alemtuzumab infusion resulted in a significant elevation in D-dimer levels within the patient group (before vs after infusion, P = .00001) and also compared with control individuals (P = .00001). PT was also prolonged in patients receiving alemtuzumab post-infusion compared with the pre-infusion values (P = .00001).
Study details: In this study, coagulation parameters were analyzed in 13 patients with MS treated with alemtuzumab and 13 control individuals.
Disclosures: The study was supported by the MH CZ-DRO, Motol University Hospital, Prague, Czech Republic. Jana Libertinova, Eva Meluzinova, Eva Nema, Petra Rockova, Martin Elisak, Marko Petrzalka, and Hana Mojzisova reported receiving compensation for travel and/or speaker honoraria and consultant fees from multiple pharmaceutical companies. The remaining authors declared no conflict of interest.
Citation: Libertinova J et al. Mult Scler. 2020 Feb 20. doi: 10.1177/1352458520904277.
Sexual dysfunction is highly prevalent in women with MS
Key clinical point: Sexual dysfunction is highly prevalent in women with multiple sclerosis (MS), and it significantly affects their quality of life.
Major finding: The overall prevalence of sexual dysfunction in women with MS was 70.3%. Sexual dysfunction in women with MS had a significant correlation with age (P = .004), duration of marriage, (P = .004), fatigue (P less than or equal to .001), Expanded Disability Status Scale (P = .004), and the combined physical and mental health aspects of quality of life (P less than .05).
Study details: The data come from a cross-sectional study that was conducted in Iran, which included 300 married women with MS aged 22-50 years.
Disclosures: The study was funded by the Isfahan University of Medical Sciences, Isfahan, Iran. The authors declared no conflict of interest.
Citation: Nazari F et al. BMC Urol. 2020 Feb 21. doi: 10.1186/s12894-020-0581-2.
Key clinical point: Sexual dysfunction is highly prevalent in women with multiple sclerosis (MS), and it significantly affects their quality of life.
Major finding: The overall prevalence of sexual dysfunction in women with MS was 70.3%. Sexual dysfunction in women with MS had a significant correlation with age (P = .004), duration of marriage, (P = .004), fatigue (P less than or equal to .001), Expanded Disability Status Scale (P = .004), and the combined physical and mental health aspects of quality of life (P less than .05).
Study details: The data come from a cross-sectional study that was conducted in Iran, which included 300 married women with MS aged 22-50 years.
Disclosures: The study was funded by the Isfahan University of Medical Sciences, Isfahan, Iran. The authors declared no conflict of interest.
Citation: Nazari F et al. BMC Urol. 2020 Feb 21. doi: 10.1186/s12894-020-0581-2.
Key clinical point: Sexual dysfunction is highly prevalent in women with multiple sclerosis (MS), and it significantly affects their quality of life.
Major finding: The overall prevalence of sexual dysfunction in women with MS was 70.3%. Sexual dysfunction in women with MS had a significant correlation with age (P = .004), duration of marriage, (P = .004), fatigue (P less than or equal to .001), Expanded Disability Status Scale (P = .004), and the combined physical and mental health aspects of quality of life (P less than .05).
Study details: The data come from a cross-sectional study that was conducted in Iran, which included 300 married women with MS aged 22-50 years.
Disclosures: The study was funded by the Isfahan University of Medical Sciences, Isfahan, Iran. The authors declared no conflict of interest.
Citation: Nazari F et al. BMC Urol. 2020 Feb 21. doi: 10.1186/s12894-020-0581-2.
Teriflunomide increases the likelihood of achieving NEDA in relapsing-remitting MS
WEST PALM BEACH, FLA. – , according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Teriflunomide reduces the risks of relapse, relapse resulting in hospital admission, and relapse resulting in prolonged hospitalization, compared with placebo.
Teriflunomide modulates the immune system and is an approved treatment for relapsing-remitting MS and clinically isolated syndrome. The phase 3 TEMSO study provided evidence that established the treatment’s safety and efficacy. In that study, significantly more patients who received a 14-mg dose of teriflunomide achieved NEDA, compared with patients who received placebo. Researchers generally weight all components of NEDA (i.e., confirmed disability worsening [CDW], relapse, and unique active MRI lesions) equally, but this approach could limit the interpretation of how each endpoint contributes to the effectiveness of a disease-modifying therapy.
A new analysis of TEMSO data
Keith R. Edwards, MD, director of the MS Center of Northeastern New York in Latham and colleagues conducted a win ratio matched-pairs analysis of TEMSO data to evaluate the efficacy of teriflunomide in enabling patients to achieve NEDA. In this analysis, the components of NEDA were assessed in order of priority, rather than as factors of equal weight.
In TEMSO, patients with relapsing-remitting MS received placebo or 14 mg of teriflunomide for 108 weeks. Dr. Edwards and colleagues matched active and control patients according to baseline characteristics. They compared the occurrence of disease activity events between the members of each pair. If a patient receiving teriflunomide had an event later than a control did, or did not have the event at all, teriflunomide was considered to “win.” If neither patient in a pair had a given event, the researchers omitted the pair from their analysis. Dr. Edwards and colleagues counted wins and summarized them as ratios. They conducted a second win ratio analysis of all relapses and relapses resulting in deaths, life-threatening events, prolonged hospitalizations, and hospital admissions.
NEDA components were ranked and assessed in the following order of decreasing priority: CDW, relapse, unique active MRI lesions. In a sensitivity analysis, the investigators ranked and assessed these components in the reverse order.
Sensitivity analysis supported primary analysis
Dr. Edwards and colleagues included 363 participants who received placebo and 358 who received teriflunomide in their analysis. Baseline characteristics did not differ significantly between the two groups. The population’s mean age was approximately 38 years, and about 73% of participants were female. The population’s mean baseline Expanded Disability Status Scale score was 2.7. Overall, about 72% of participants completed the study.
The researchers created 321 risk-matched pairs of participants. The win ratio analysis indicated that patients who received teriflunomide were significantly more likely to achieve NEDA, compared with controls (win ratio, 1.33). When the investigators analyzed the data by prioritizing the NEDA components in the reverse order, they found similar results (win ratio, 1.41).
When Dr. Edwards and colleagues analyzed relapse severity, they found that no relapses resulting in death or life-threatening events occurred in the active or control groups. Compared with placebo, teriflunomide significantly reduced the risk of relapse, relapses resulting in hospital admissions, and relapses resulting in prolonged hospitalizations (win ratio, 1.37).
The TEMSO study was funded by Sanofi. Dr. Edwards received grant or research support from Biogen, Genentech, Genzyme, and Novartis. Several authors received funding from Sanofi.
SOURCE: Edwards KR et al. ACTRIMS 2020, Abstract P036.
WEST PALM BEACH, FLA. – , according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Teriflunomide reduces the risks of relapse, relapse resulting in hospital admission, and relapse resulting in prolonged hospitalization, compared with placebo.
Teriflunomide modulates the immune system and is an approved treatment for relapsing-remitting MS and clinically isolated syndrome. The phase 3 TEMSO study provided evidence that established the treatment’s safety and efficacy. In that study, significantly more patients who received a 14-mg dose of teriflunomide achieved NEDA, compared with patients who received placebo. Researchers generally weight all components of NEDA (i.e., confirmed disability worsening [CDW], relapse, and unique active MRI lesions) equally, but this approach could limit the interpretation of how each endpoint contributes to the effectiveness of a disease-modifying therapy.
A new analysis of TEMSO data
Keith R. Edwards, MD, director of the MS Center of Northeastern New York in Latham and colleagues conducted a win ratio matched-pairs analysis of TEMSO data to evaluate the efficacy of teriflunomide in enabling patients to achieve NEDA. In this analysis, the components of NEDA were assessed in order of priority, rather than as factors of equal weight.
In TEMSO, patients with relapsing-remitting MS received placebo or 14 mg of teriflunomide for 108 weeks. Dr. Edwards and colleagues matched active and control patients according to baseline characteristics. They compared the occurrence of disease activity events between the members of each pair. If a patient receiving teriflunomide had an event later than a control did, or did not have the event at all, teriflunomide was considered to “win.” If neither patient in a pair had a given event, the researchers omitted the pair from their analysis. Dr. Edwards and colleagues counted wins and summarized them as ratios. They conducted a second win ratio analysis of all relapses and relapses resulting in deaths, life-threatening events, prolonged hospitalizations, and hospital admissions.
NEDA components were ranked and assessed in the following order of decreasing priority: CDW, relapse, unique active MRI lesions. In a sensitivity analysis, the investigators ranked and assessed these components in the reverse order.
Sensitivity analysis supported primary analysis
Dr. Edwards and colleagues included 363 participants who received placebo and 358 who received teriflunomide in their analysis. Baseline characteristics did not differ significantly between the two groups. The population’s mean age was approximately 38 years, and about 73% of participants were female. The population’s mean baseline Expanded Disability Status Scale score was 2.7. Overall, about 72% of participants completed the study.
The researchers created 321 risk-matched pairs of participants. The win ratio analysis indicated that patients who received teriflunomide were significantly more likely to achieve NEDA, compared with controls (win ratio, 1.33). When the investigators analyzed the data by prioritizing the NEDA components in the reverse order, they found similar results (win ratio, 1.41).
When Dr. Edwards and colleagues analyzed relapse severity, they found that no relapses resulting in death or life-threatening events occurred in the active or control groups. Compared with placebo, teriflunomide significantly reduced the risk of relapse, relapses resulting in hospital admissions, and relapses resulting in prolonged hospitalizations (win ratio, 1.37).
The TEMSO study was funded by Sanofi. Dr. Edwards received grant or research support from Biogen, Genentech, Genzyme, and Novartis. Several authors received funding from Sanofi.
SOURCE: Edwards KR et al. ACTRIMS 2020, Abstract P036.
WEST PALM BEACH, FLA. – , according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Teriflunomide reduces the risks of relapse, relapse resulting in hospital admission, and relapse resulting in prolonged hospitalization, compared with placebo.
Teriflunomide modulates the immune system and is an approved treatment for relapsing-remitting MS and clinically isolated syndrome. The phase 3 TEMSO study provided evidence that established the treatment’s safety and efficacy. In that study, significantly more patients who received a 14-mg dose of teriflunomide achieved NEDA, compared with patients who received placebo. Researchers generally weight all components of NEDA (i.e., confirmed disability worsening [CDW], relapse, and unique active MRI lesions) equally, but this approach could limit the interpretation of how each endpoint contributes to the effectiveness of a disease-modifying therapy.
A new analysis of TEMSO data
Keith R. Edwards, MD, director of the MS Center of Northeastern New York in Latham and colleagues conducted a win ratio matched-pairs analysis of TEMSO data to evaluate the efficacy of teriflunomide in enabling patients to achieve NEDA. In this analysis, the components of NEDA were assessed in order of priority, rather than as factors of equal weight.
In TEMSO, patients with relapsing-remitting MS received placebo or 14 mg of teriflunomide for 108 weeks. Dr. Edwards and colleagues matched active and control patients according to baseline characteristics. They compared the occurrence of disease activity events between the members of each pair. If a patient receiving teriflunomide had an event later than a control did, or did not have the event at all, teriflunomide was considered to “win.” If neither patient in a pair had a given event, the researchers omitted the pair from their analysis. Dr. Edwards and colleagues counted wins and summarized them as ratios. They conducted a second win ratio analysis of all relapses and relapses resulting in deaths, life-threatening events, prolonged hospitalizations, and hospital admissions.
NEDA components were ranked and assessed in the following order of decreasing priority: CDW, relapse, unique active MRI lesions. In a sensitivity analysis, the investigators ranked and assessed these components in the reverse order.
Sensitivity analysis supported primary analysis
Dr. Edwards and colleagues included 363 participants who received placebo and 358 who received teriflunomide in their analysis. Baseline characteristics did not differ significantly between the two groups. The population’s mean age was approximately 38 years, and about 73% of participants were female. The population’s mean baseline Expanded Disability Status Scale score was 2.7. Overall, about 72% of participants completed the study.
The researchers created 321 risk-matched pairs of participants. The win ratio analysis indicated that patients who received teriflunomide were significantly more likely to achieve NEDA, compared with controls (win ratio, 1.33). When the investigators analyzed the data by prioritizing the NEDA components in the reverse order, they found similar results (win ratio, 1.41).
When Dr. Edwards and colleagues analyzed relapse severity, they found that no relapses resulting in death or life-threatening events occurred in the active or control groups. Compared with placebo, teriflunomide significantly reduced the risk of relapse, relapses resulting in hospital admissions, and relapses resulting in prolonged hospitalizations (win ratio, 1.37).
The TEMSO study was funded by Sanofi. Dr. Edwards received grant or research support from Biogen, Genentech, Genzyme, and Novartis. Several authors received funding from Sanofi.
SOURCE: Edwards KR et al. ACTRIMS 2020, Abstract P036.
REPORTING FROM ACTRIMS Forum 2020
Manual dexterity may decline more rapidly in pediatric-onset MS
WEST PALM BEACH, FLA. – (AOMS), according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
When MS onset occurs before the patient is age 18 years, the patient is considered to have POMS. Compared with AOMS, POMS is less prevalent and has distinct features. To determine whether changes in physical performance differ between POMS and AOMS, Sarah M. Planchon, PhD, a project scientist at the Mellen Center for MS at the Cleveland Clinic, and colleagues analyzed data cut 9 from the MS PATHS (MS Partners Advancing Technology and Health Solutions) initiative. As part of this initiative, which is sponsored by Biogen, investigators collect MS performance measures longitudinally at each patient visit. Among these measures are the manual dexterity test (MDT), an iPad version of the Nine-Hole Peg Test, and the walking speed test (WST), which is the iPad version of the Timed 25-Foot Walk.
Dr. Planchon and colleagues matched each patient with POMS to five patients with AOMS according to disease duration. They calculated descriptive statistics for the sample and performed Tukey’s honestly significant difference test to compare patient groups on several categorical variables.
Overall, function was better in POMS than in AOMS
The investigators included 3 years’ worth of data from 6,457 patients in their analysis. The average age was approximately 50 years for patients with AOMS and 31 years for patients with POMS. The time elapsed since diagnosis was approximately 14 years in the AOMS group and 17 years in the POMS group. The proportion of female patients was about 74% in the AOMS group and 73% in the POMS group. Compared with the AOMS group, the POMS group had higher proportions of patients who were Asian (0.5% vs 2.6%), black (9.3% vs 11.5%), and other race (2.8% vs 9.3%).
Overall, patients with POMS performed better than patients with AOMS by 1.39 seconds on the MDT and by 0.79 seconds on the WST. Regression analyses indicated that with increasing age, patients with AOMS declined more quickly on the MDT and the WST than patients with POMS did. When the investigators stratified the results by disease duration, however, patients with POMS declined more rapidly on the MDT than did patients with AOMS. There was no significant difference between groups in WST in this analysis. When Dr. Planchon and colleagues performed linear regression and adjusted for variables such as age, sex, race, education, insurance, employment, MS phenotype, disease duration, number of relapses, and Patient-Determined Disease Steps (PDDS), the MS onset type did not significantly affect outcomes. Age, sex, PDDS, and MS type were significant covariates for both tests.
The role of occupational and physical therapy
“POMS patients tend to have a greater dysfunction of the cerebellar and brainstem regions of the brain, both of which may impact motor skills to a greater degree than other regions of the brain,” said Dr. Planchon. The increased rate of manual impairment in POMS, compared with AOMS, does not necessarily indicate more severe disease, she added. Getting a true picture of disease severity would require consideration of factors such as ambulation, cognitive functioning, vision, fatigue, and depression.
“We would recommend introducing POMS patients to occupational and physical therapy early in their disease course, before significant deficits accrue,” said Dr. Planchon. “Early familiarity with rehabilitation services should help the patient and family optimize what exercises are being done to improve and maintain function.”
The optimal pharmacologic treatment for POMS is unknown. One therapy (i.e., fingolimod) has Food and Drug Administration approval, and clinical trials of other treatments are ongoing. Some MS treatments not indicated for a pediatric population are used off label in children.
“We plan to delve deeper into the data set, including using regression modeling to try to better define differences between individuals with POMS and AOMS that may lead to the functional outcome changes we have already observed,” said Dr. Planchon. “We also plan to investigate further the impact of POMS on cognition and quality of life measures and to better understand disease-modifying therapy prescribing patterns and benefits in individuals with POMS. We will look for associations in the MRI imaging findings and various biomarkers to help us understand the disease process in this special population of MS.”
Dr. Planchon has received research support from the Guthy-Jackson Charitable Foundation. Her coinvestigators received funding from Biogen, Genentech, Genzyme, MedImmune, Novartis, Serono, and Teva.
SOURCE: Planchon SM et al. ACTRIMS 2020. Abstract P043.
WEST PALM BEACH, FLA. – (AOMS), according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
When MS onset occurs before the patient is age 18 years, the patient is considered to have POMS. Compared with AOMS, POMS is less prevalent and has distinct features. To determine whether changes in physical performance differ between POMS and AOMS, Sarah M. Planchon, PhD, a project scientist at the Mellen Center for MS at the Cleveland Clinic, and colleagues analyzed data cut 9 from the MS PATHS (MS Partners Advancing Technology and Health Solutions) initiative. As part of this initiative, which is sponsored by Biogen, investigators collect MS performance measures longitudinally at each patient visit. Among these measures are the manual dexterity test (MDT), an iPad version of the Nine-Hole Peg Test, and the walking speed test (WST), which is the iPad version of the Timed 25-Foot Walk.
Dr. Planchon and colleagues matched each patient with POMS to five patients with AOMS according to disease duration. They calculated descriptive statistics for the sample and performed Tukey’s honestly significant difference test to compare patient groups on several categorical variables.
Overall, function was better in POMS than in AOMS
The investigators included 3 years’ worth of data from 6,457 patients in their analysis. The average age was approximately 50 years for patients with AOMS and 31 years for patients with POMS. The time elapsed since diagnosis was approximately 14 years in the AOMS group and 17 years in the POMS group. The proportion of female patients was about 74% in the AOMS group and 73% in the POMS group. Compared with the AOMS group, the POMS group had higher proportions of patients who were Asian (0.5% vs 2.6%), black (9.3% vs 11.5%), and other race (2.8% vs 9.3%).
Overall, patients with POMS performed better than patients with AOMS by 1.39 seconds on the MDT and by 0.79 seconds on the WST. Regression analyses indicated that with increasing age, patients with AOMS declined more quickly on the MDT and the WST than patients with POMS did. When the investigators stratified the results by disease duration, however, patients with POMS declined more rapidly on the MDT than did patients with AOMS. There was no significant difference between groups in WST in this analysis. When Dr. Planchon and colleagues performed linear regression and adjusted for variables such as age, sex, race, education, insurance, employment, MS phenotype, disease duration, number of relapses, and Patient-Determined Disease Steps (PDDS), the MS onset type did not significantly affect outcomes. Age, sex, PDDS, and MS type were significant covariates for both tests.
The role of occupational and physical therapy
“POMS patients tend to have a greater dysfunction of the cerebellar and brainstem regions of the brain, both of which may impact motor skills to a greater degree than other regions of the brain,” said Dr. Planchon. The increased rate of manual impairment in POMS, compared with AOMS, does not necessarily indicate more severe disease, she added. Getting a true picture of disease severity would require consideration of factors such as ambulation, cognitive functioning, vision, fatigue, and depression.
“We would recommend introducing POMS patients to occupational and physical therapy early in their disease course, before significant deficits accrue,” said Dr. Planchon. “Early familiarity with rehabilitation services should help the patient and family optimize what exercises are being done to improve and maintain function.”
The optimal pharmacologic treatment for POMS is unknown. One therapy (i.e., fingolimod) has Food and Drug Administration approval, and clinical trials of other treatments are ongoing. Some MS treatments not indicated for a pediatric population are used off label in children.
“We plan to delve deeper into the data set, including using regression modeling to try to better define differences between individuals with POMS and AOMS that may lead to the functional outcome changes we have already observed,” said Dr. Planchon. “We also plan to investigate further the impact of POMS on cognition and quality of life measures and to better understand disease-modifying therapy prescribing patterns and benefits in individuals with POMS. We will look for associations in the MRI imaging findings and various biomarkers to help us understand the disease process in this special population of MS.”
Dr. Planchon has received research support from the Guthy-Jackson Charitable Foundation. Her coinvestigators received funding from Biogen, Genentech, Genzyme, MedImmune, Novartis, Serono, and Teva.
SOURCE: Planchon SM et al. ACTRIMS 2020. Abstract P043.
WEST PALM BEACH, FLA. – (AOMS), according to an analysis presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
When MS onset occurs before the patient is age 18 years, the patient is considered to have POMS. Compared with AOMS, POMS is less prevalent and has distinct features. To determine whether changes in physical performance differ between POMS and AOMS, Sarah M. Planchon, PhD, a project scientist at the Mellen Center for MS at the Cleveland Clinic, and colleagues analyzed data cut 9 from the MS PATHS (MS Partners Advancing Technology and Health Solutions) initiative. As part of this initiative, which is sponsored by Biogen, investigators collect MS performance measures longitudinally at each patient visit. Among these measures are the manual dexterity test (MDT), an iPad version of the Nine-Hole Peg Test, and the walking speed test (WST), which is the iPad version of the Timed 25-Foot Walk.
Dr. Planchon and colleagues matched each patient with POMS to five patients with AOMS according to disease duration. They calculated descriptive statistics for the sample and performed Tukey’s honestly significant difference test to compare patient groups on several categorical variables.
Overall, function was better in POMS than in AOMS
The investigators included 3 years’ worth of data from 6,457 patients in their analysis. The average age was approximately 50 years for patients with AOMS and 31 years for patients with POMS. The time elapsed since diagnosis was approximately 14 years in the AOMS group and 17 years in the POMS group. The proportion of female patients was about 74% in the AOMS group and 73% in the POMS group. Compared with the AOMS group, the POMS group had higher proportions of patients who were Asian (0.5% vs 2.6%), black (9.3% vs 11.5%), and other race (2.8% vs 9.3%).
Overall, patients with POMS performed better than patients with AOMS by 1.39 seconds on the MDT and by 0.79 seconds on the WST. Regression analyses indicated that with increasing age, patients with AOMS declined more quickly on the MDT and the WST than patients with POMS did. When the investigators stratified the results by disease duration, however, patients with POMS declined more rapidly on the MDT than did patients with AOMS. There was no significant difference between groups in WST in this analysis. When Dr. Planchon and colleagues performed linear regression and adjusted for variables such as age, sex, race, education, insurance, employment, MS phenotype, disease duration, number of relapses, and Patient-Determined Disease Steps (PDDS), the MS onset type did not significantly affect outcomes. Age, sex, PDDS, and MS type were significant covariates for both tests.
The role of occupational and physical therapy
“POMS patients tend to have a greater dysfunction of the cerebellar and brainstem regions of the brain, both of which may impact motor skills to a greater degree than other regions of the brain,” said Dr. Planchon. The increased rate of manual impairment in POMS, compared with AOMS, does not necessarily indicate more severe disease, she added. Getting a true picture of disease severity would require consideration of factors such as ambulation, cognitive functioning, vision, fatigue, and depression.
“We would recommend introducing POMS patients to occupational and physical therapy early in their disease course, before significant deficits accrue,” said Dr. Planchon. “Early familiarity with rehabilitation services should help the patient and family optimize what exercises are being done to improve and maintain function.”
The optimal pharmacologic treatment for POMS is unknown. One therapy (i.e., fingolimod) has Food and Drug Administration approval, and clinical trials of other treatments are ongoing. Some MS treatments not indicated for a pediatric population are used off label in children.
“We plan to delve deeper into the data set, including using regression modeling to try to better define differences between individuals with POMS and AOMS that may lead to the functional outcome changes we have already observed,” said Dr. Planchon. “We also plan to investigate further the impact of POMS on cognition and quality of life measures and to better understand disease-modifying therapy prescribing patterns and benefits in individuals with POMS. We will look for associations in the MRI imaging findings and various biomarkers to help us understand the disease process in this special population of MS.”
Dr. Planchon has received research support from the Guthy-Jackson Charitable Foundation. Her coinvestigators received funding from Biogen, Genentech, Genzyme, MedImmune, Novartis, Serono, and Teva.
SOURCE: Planchon SM et al. ACTRIMS 2020. Abstract P043.
REPORTING FROM ACTRIMS FORUM 2020
DMT use is common in older patients with MS
WEST PALM BEACH, FLA. –
MS disease activity typically declines with age. At the same time, evidence to support the efficacy of MS drugs in older patients is limited, said Yinan Zhang, MD, a researcher at Icahn School of Medicine at Mount Sinai, New York. Clinical trials have tended to enroll younger patients and to include only patients with active disease, which is not representative of most older patients in the real world, Dr. Zhang said.
“DMTs for MS may be less efficacious in the elderly, especially in the absence of active disease, yet real-world prescribing patterns still show widespread use of DMTs in older patients,” Dr. Zhang and colleagues said. Physicians may be able to use the presence of disease activity to identify older patients who should receive therapy. “Continuing DMTs in elderly patients who have no evidence of disease activity should be questioned rather than accepted,” they said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To investigate whether age affects the efficacy of DMTs in patients with relapsing-remitting MS and how often DMTs are used in different age groups, Dr. Zhang and coinvestigators conducted a meta-analysis of group-level data from clinical trial, analyzed individual-level data from one of the trials, and reviewed survey data from two registries.
The meta-analysis included 26 clinical trials of 13 DMTs with more than 12,400 patients. Participants had an average age of about 37 years. “An age-dependent relationship of DMTs on relapse rate in RRMS [relapsing-remitting MS] cannot be established with currently published aggregate summary data,” the researchers said. “The meta-analysis was limited by the use of group-level data resulting in a narrow range of mean age.”
In an effort to overcome the limitations of group-level data, they analyzed individual-level data from approximately 1,000 patients in the CombiRx trial, which compared interferon beta-1a plus glatiramer acetate versus the agents alone. Thirty-seven of the patients were aged 55 years or older. The results suggest that each “1-year increase in baseline age was associated with a 3.2% reduction in the odds of having a relapse” during the trial, the investigators said. Change in annualized relapse rate was not significantly associated with age group, which may have resulted from “enrollment criteria selecting for patients with active disease, where DMTs are expected to show the greatest efficacy,” the researchers said.
Finally, Dr. Zhang and colleagues reviewed data on DMT use by age group from the North American Research Committee on Multiple Sclerosis (NARCOMS) and the Multiple Sclerosis Surveillance Registry (MSSR) from Veterans Affairs. In a 2018 survey of nearly 7,000 patients in the NARCOMS registry, 39.2% of patients older than 60 years were taking a DMT, including 44.5% of patients aged 61-70, 28.6% of patients aged 71-80, and 11% of patients aged 81 years and older. In comparison, about 62% of patients aged 41-50 years were taking DMT.
A 2019 survey of about 1,700 veterans in the MSSR found that 36.3% of patients older than 60 years were taking a DMT, including 41.1% of patients aged 61-70, 27.2% of patients aged 71-80, and 7.1% of patients aged 81 years and older. Among patients aged 41-50 years, more than 72% were taking a DMT. “The continued use of DMTs in the elderly may be the result of the perceived notion that disease inactivity is due to the effect of DMTs rather than the natural disease course with aging,” they said.
Dr. Zhang had no relevant disclosures. Coauthors disclosed consulting for and grant support from various pharmaceutical companies.
SOURCE: Zhang Y et al. ACTRIMS Forum 2020. Abstract P263.
WEST PALM BEACH, FLA. –
MS disease activity typically declines with age. At the same time, evidence to support the efficacy of MS drugs in older patients is limited, said Yinan Zhang, MD, a researcher at Icahn School of Medicine at Mount Sinai, New York. Clinical trials have tended to enroll younger patients and to include only patients with active disease, which is not representative of most older patients in the real world, Dr. Zhang said.
“DMTs for MS may be less efficacious in the elderly, especially in the absence of active disease, yet real-world prescribing patterns still show widespread use of DMTs in older patients,” Dr. Zhang and colleagues said. Physicians may be able to use the presence of disease activity to identify older patients who should receive therapy. “Continuing DMTs in elderly patients who have no evidence of disease activity should be questioned rather than accepted,” they said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To investigate whether age affects the efficacy of DMTs in patients with relapsing-remitting MS and how often DMTs are used in different age groups, Dr. Zhang and coinvestigators conducted a meta-analysis of group-level data from clinical trial, analyzed individual-level data from one of the trials, and reviewed survey data from two registries.
The meta-analysis included 26 clinical trials of 13 DMTs with more than 12,400 patients. Participants had an average age of about 37 years. “An age-dependent relationship of DMTs on relapse rate in RRMS [relapsing-remitting MS] cannot be established with currently published aggregate summary data,” the researchers said. “The meta-analysis was limited by the use of group-level data resulting in a narrow range of mean age.”
In an effort to overcome the limitations of group-level data, they analyzed individual-level data from approximately 1,000 patients in the CombiRx trial, which compared interferon beta-1a plus glatiramer acetate versus the agents alone. Thirty-seven of the patients were aged 55 years or older. The results suggest that each “1-year increase in baseline age was associated with a 3.2% reduction in the odds of having a relapse” during the trial, the investigators said. Change in annualized relapse rate was not significantly associated with age group, which may have resulted from “enrollment criteria selecting for patients with active disease, where DMTs are expected to show the greatest efficacy,” the researchers said.
Finally, Dr. Zhang and colleagues reviewed data on DMT use by age group from the North American Research Committee on Multiple Sclerosis (NARCOMS) and the Multiple Sclerosis Surveillance Registry (MSSR) from Veterans Affairs. In a 2018 survey of nearly 7,000 patients in the NARCOMS registry, 39.2% of patients older than 60 years were taking a DMT, including 44.5% of patients aged 61-70, 28.6% of patients aged 71-80, and 11% of patients aged 81 years and older. In comparison, about 62% of patients aged 41-50 years were taking DMT.
A 2019 survey of about 1,700 veterans in the MSSR found that 36.3% of patients older than 60 years were taking a DMT, including 41.1% of patients aged 61-70, 27.2% of patients aged 71-80, and 7.1% of patients aged 81 years and older. Among patients aged 41-50 years, more than 72% were taking a DMT. “The continued use of DMTs in the elderly may be the result of the perceived notion that disease inactivity is due to the effect of DMTs rather than the natural disease course with aging,” they said.
Dr. Zhang had no relevant disclosures. Coauthors disclosed consulting for and grant support from various pharmaceutical companies.
SOURCE: Zhang Y et al. ACTRIMS Forum 2020. Abstract P263.
WEST PALM BEACH, FLA. –
MS disease activity typically declines with age. At the same time, evidence to support the efficacy of MS drugs in older patients is limited, said Yinan Zhang, MD, a researcher at Icahn School of Medicine at Mount Sinai, New York. Clinical trials have tended to enroll younger patients and to include only patients with active disease, which is not representative of most older patients in the real world, Dr. Zhang said.
“DMTs for MS may be less efficacious in the elderly, especially in the absence of active disease, yet real-world prescribing patterns still show widespread use of DMTs in older patients,” Dr. Zhang and colleagues said. Physicians may be able to use the presence of disease activity to identify older patients who should receive therapy. “Continuing DMTs in elderly patients who have no evidence of disease activity should be questioned rather than accepted,” they said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
To investigate whether age affects the efficacy of DMTs in patients with relapsing-remitting MS and how often DMTs are used in different age groups, Dr. Zhang and coinvestigators conducted a meta-analysis of group-level data from clinical trial, analyzed individual-level data from one of the trials, and reviewed survey data from two registries.
The meta-analysis included 26 clinical trials of 13 DMTs with more than 12,400 patients. Participants had an average age of about 37 years. “An age-dependent relationship of DMTs on relapse rate in RRMS [relapsing-remitting MS] cannot be established with currently published aggregate summary data,” the researchers said. “The meta-analysis was limited by the use of group-level data resulting in a narrow range of mean age.”
In an effort to overcome the limitations of group-level data, they analyzed individual-level data from approximately 1,000 patients in the CombiRx trial, which compared interferon beta-1a plus glatiramer acetate versus the agents alone. Thirty-seven of the patients were aged 55 years or older. The results suggest that each “1-year increase in baseline age was associated with a 3.2% reduction in the odds of having a relapse” during the trial, the investigators said. Change in annualized relapse rate was not significantly associated with age group, which may have resulted from “enrollment criteria selecting for patients with active disease, where DMTs are expected to show the greatest efficacy,” the researchers said.
Finally, Dr. Zhang and colleagues reviewed data on DMT use by age group from the North American Research Committee on Multiple Sclerosis (NARCOMS) and the Multiple Sclerosis Surveillance Registry (MSSR) from Veterans Affairs. In a 2018 survey of nearly 7,000 patients in the NARCOMS registry, 39.2% of patients older than 60 years were taking a DMT, including 44.5% of patients aged 61-70, 28.6% of patients aged 71-80, and 11% of patients aged 81 years and older. In comparison, about 62% of patients aged 41-50 years were taking DMT.
A 2019 survey of about 1,700 veterans in the MSSR found that 36.3% of patients older than 60 years were taking a DMT, including 41.1% of patients aged 61-70, 27.2% of patients aged 71-80, and 7.1% of patients aged 81 years and older. Among patients aged 41-50 years, more than 72% were taking a DMT. “The continued use of DMTs in the elderly may be the result of the perceived notion that disease inactivity is due to the effect of DMTs rather than the natural disease course with aging,” they said.
Dr. Zhang had no relevant disclosures. Coauthors disclosed consulting for and grant support from various pharmaceutical companies.
SOURCE: Zhang Y et al. ACTRIMS Forum 2020. Abstract P263.
REPORTING FROM ACTRIMS FORUM 2020
Serum GFAP may indicate disease severity in NMOSD
WEST PALM BEACH, FLA. – (NMOSD), according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Treatment with inebilizumab decreases serum GFAP concentrations and reduces the risk of an NMOSD attack, the investigators said.
In NMOSD, autoantibodies often target aquaporin-4, a protein expressed on astrocytes. This immune response destroys astrocytes and increases levels of GFAP in cerebrospinal fluid and serum. In the N-MOmentum trial, inebilizumab reduced the risk of attacks by 73%, compared with placebo, in patients with NMOSD. Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences and colleagues analyzed the data from this trial to examine the relationship between serum GFAP concentrations and disease activity.
In the study, the investigators prospectively collected 1,260 serum samples from 215 participants, 25 healthy donors, and 23 patients with relapsing-remitting multiple sclerosis (MS). Serum GFAP concentration was measured using a single-molecule array assay. The researchers and an independent adjudication committee evaluated attacks during the 28-week randomized controlled study period using predefined criteria.
The median serum GFAP concentration was higher in patients with NMOSD (128.3 pg/mL) than in patients with relapsing-remitting MS (97.5 pg/mL) and healthy controls (73.3 pg/mL). At baseline, 29% of patients with NMOSD and 9% of patients with MS had a serum GFAP concentration that was three or more standard deviations above the mean level in healthy donors.
During the study, patients with a high baseline concentration of serum GFAP were three times more likely to have an adjudicated NMOSD attack than patients with lower serum GFAP concentrations. Concentrations of serum GFAP increased within 1 week of an adjudicated attack during the randomized controlled period. Furthermore, serum GFAP concentration was significantly higher in patients with major adjudicated attacks, compared with those who had minor adjudicated attacks. This finding was true for all organ domains, including for attacks that affected only the optic nerve.
Compared with placebo, inebilizumab reduced the risk of an adjudicated attack by 79% in patients with a normal baseline serum GFAP concentration and by 61% in patients with an elevated baseline serum GFAP concentration. The increase in serum GFAP concentration following an adjudicated attack was significant in patients receiving placebo, but not in patients receiving inebilizumab. Seven samples taken during an adjudicated attack from patients receiving inebilizumab had serum GFAP concentrations within the normal range. One sample taken during an attack from a patient receiving placebo had a serum GFAP concentration within the normal range. In addition, serum GFAP concentrations decreased from baseline among patients receiving inebilizumab who did not have an adjudicated attack.
“These observations suggest that serum GFAP could be a clinically useful biomarker of disease activity and increased attack risk in NMOSD,” said Dr. Cree and colleagues.
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: Hartung H et al. ACTRIMS 2020, Abstract P205.
WEST PALM BEACH, FLA. – (NMOSD), according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Treatment with inebilizumab decreases serum GFAP concentrations and reduces the risk of an NMOSD attack, the investigators said.
In NMOSD, autoantibodies often target aquaporin-4, a protein expressed on astrocytes. This immune response destroys astrocytes and increases levels of GFAP in cerebrospinal fluid and serum. In the N-MOmentum trial, inebilizumab reduced the risk of attacks by 73%, compared with placebo, in patients with NMOSD. Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences and colleagues analyzed the data from this trial to examine the relationship between serum GFAP concentrations and disease activity.
In the study, the investigators prospectively collected 1,260 serum samples from 215 participants, 25 healthy donors, and 23 patients with relapsing-remitting multiple sclerosis (MS). Serum GFAP concentration was measured using a single-molecule array assay. The researchers and an independent adjudication committee evaluated attacks during the 28-week randomized controlled study period using predefined criteria.
The median serum GFAP concentration was higher in patients with NMOSD (128.3 pg/mL) than in patients with relapsing-remitting MS (97.5 pg/mL) and healthy controls (73.3 pg/mL). At baseline, 29% of patients with NMOSD and 9% of patients with MS had a serum GFAP concentration that was three or more standard deviations above the mean level in healthy donors.
During the study, patients with a high baseline concentration of serum GFAP were three times more likely to have an adjudicated NMOSD attack than patients with lower serum GFAP concentrations. Concentrations of serum GFAP increased within 1 week of an adjudicated attack during the randomized controlled period. Furthermore, serum GFAP concentration was significantly higher in patients with major adjudicated attacks, compared with those who had minor adjudicated attacks. This finding was true for all organ domains, including for attacks that affected only the optic nerve.
Compared with placebo, inebilizumab reduced the risk of an adjudicated attack by 79% in patients with a normal baseline serum GFAP concentration and by 61% in patients with an elevated baseline serum GFAP concentration. The increase in serum GFAP concentration following an adjudicated attack was significant in patients receiving placebo, but not in patients receiving inebilizumab. Seven samples taken during an adjudicated attack from patients receiving inebilizumab had serum GFAP concentrations within the normal range. One sample taken during an attack from a patient receiving placebo had a serum GFAP concentration within the normal range. In addition, serum GFAP concentrations decreased from baseline among patients receiving inebilizumab who did not have an adjudicated attack.
“These observations suggest that serum GFAP could be a clinically useful biomarker of disease activity and increased attack risk in NMOSD,” said Dr. Cree and colleagues.
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: Hartung H et al. ACTRIMS 2020, Abstract P205.
WEST PALM BEACH, FLA. – (NMOSD), according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Treatment with inebilizumab decreases serum GFAP concentrations and reduces the risk of an NMOSD attack, the investigators said.
In NMOSD, autoantibodies often target aquaporin-4, a protein expressed on astrocytes. This immune response destroys astrocytes and increases levels of GFAP in cerebrospinal fluid and serum. In the N-MOmentum trial, inebilizumab reduced the risk of attacks by 73%, compared with placebo, in patients with NMOSD. Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences and colleagues analyzed the data from this trial to examine the relationship between serum GFAP concentrations and disease activity.
In the study, the investigators prospectively collected 1,260 serum samples from 215 participants, 25 healthy donors, and 23 patients with relapsing-remitting multiple sclerosis (MS). Serum GFAP concentration was measured using a single-molecule array assay. The researchers and an independent adjudication committee evaluated attacks during the 28-week randomized controlled study period using predefined criteria.
The median serum GFAP concentration was higher in patients with NMOSD (128.3 pg/mL) than in patients with relapsing-remitting MS (97.5 pg/mL) and healthy controls (73.3 pg/mL). At baseline, 29% of patients with NMOSD and 9% of patients with MS had a serum GFAP concentration that was three or more standard deviations above the mean level in healthy donors.
During the study, patients with a high baseline concentration of serum GFAP were three times more likely to have an adjudicated NMOSD attack than patients with lower serum GFAP concentrations. Concentrations of serum GFAP increased within 1 week of an adjudicated attack during the randomized controlled period. Furthermore, serum GFAP concentration was significantly higher in patients with major adjudicated attacks, compared with those who had minor adjudicated attacks. This finding was true for all organ domains, including for attacks that affected only the optic nerve.
Compared with placebo, inebilizumab reduced the risk of an adjudicated attack by 79% in patients with a normal baseline serum GFAP concentration and by 61% in patients with an elevated baseline serum GFAP concentration. The increase in serum GFAP concentration following an adjudicated attack was significant in patients receiving placebo, but not in patients receiving inebilizumab. Seven samples taken during an adjudicated attack from patients receiving inebilizumab had serum GFAP concentrations within the normal range. One sample taken during an attack from a patient receiving placebo had a serum GFAP concentration within the normal range. In addition, serum GFAP concentrations decreased from baseline among patients receiving inebilizumab who did not have an adjudicated attack.
“These observations suggest that serum GFAP could be a clinically useful biomarker of disease activity and increased attack risk in NMOSD,” said Dr. Cree and colleagues.
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: Hartung H et al. ACTRIMS 2020, Abstract P205.
REPORTING FROM ACTRIMS FORUM 2020
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