Multiple Sclerosis

A shift in managing symptoms for patients with relapsing-remitting multiple sclerosis (RRMS) may be in order as new research questions the efficacy of three commonly used drugs for MS-related fatigue. Results of a study from Johns Hopkins University show that amantadine, modafinil, and methylphenidate were not superior to placebo. As Dr Mark Freedman reports in this ReCAP, the study suggests that clinicians consider focusing more on patient sleep quality rather than tiredness in their evaluation of fatigue.

This study was presented during the 8th Joint Meeting of ACTRIMS-ECTRIMS, this year branded MSVirtual2020. Dr Freedman, a recognized neurologist from the University of Ottawa, shares key highlights from the online conference.

He explains the significance of new evidence that points to the potential for a selective retinoid X receptor agonist to promote remyelination in relapsing disease. He also discusses a study by researchers at the University of Melbourne that looked at data from the largest cohort of MS patients with COVID-19 and drew troubling conclusions.

Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; Director, Multiple Sclerosis Research Unit, The Ottawa Hospital – General Campus, Ottawa, Ontario, Canada.

Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships: Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson & Johnson); Alexion; Atara Biotherapeutics; BayerHealthcare; BiogenIdec; Celgene; Clene Nanomedicine; GRI Bio; Hoffman La-Roche; Magenta Therapeutics; Merck Serono; MedDay; Novartis; Sanofi-Genzyme; Teva Canada Innovation. Serve(d) as a member of a speakers bureau for: Sanofi-Genzyme; EMD Serono. Received honoraria or consultation fees for: Actelion (Janssen/Johnson & Johnson); Alexion; BiogenIdec; Celgene (BMS); EMD Inc; Sanofi-Genzyme; Hoffman La-Roche; Merck Serono; Novartis; Teva Canada Innovation­. Received research or educational grants from: Sanofi-Genzyme Canada; Hoffman-La Roche; EMD Inc.

A shift in managing symptoms for patients with relapsing-remitting multiple sclerosis (RRMS) may be in order as new research questions the efficacy of three commonly used drugs for MS-related fatigue. Results of a study from Johns Hopkins University show that amantadine, modafinil, and methylphenidate were not superior to placebo. As Dr Mark Freedman reports in this ReCAP, the study suggests that clinicians consider focusing more on patient sleep quality rather than tiredness in their evaluation of fatigue.

This study was presented during the 8th Joint Meeting of ACTRIMS-ECTRIMS, this year branded MSVirtual2020. Dr Freedman, a recognized neurologist from the University of Ottawa, shares key highlights from the online conference.

He explains the significance of new evidence that points to the potential for a selective retinoid X receptor agonist to promote remyelination in relapsing disease. He also discusses a study by researchers at the University of Melbourne that looked at data from the largest cohort of MS patients with COVID-19 and drew troubling conclusions.

Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; Director, Multiple Sclerosis Research Unit, The Ottawa Hospital – General Campus, Ottawa, Ontario, Canada.

Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships: Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson & Johnson); Alexion; Atara Biotherapeutics; BayerHealthcare; BiogenIdec; Celgene; Clene Nanomedicine; GRI Bio; Hoffman La-Roche; Magenta Therapeutics; Merck Serono; MedDay; Novartis; Sanofi-Genzyme; Teva Canada Innovation. Serve(d) as a member of a speakers bureau for: Sanofi-Genzyme; EMD Serono. Received honoraria or consultation fees for: Actelion (Janssen/Johnson & Johnson); Alexion; BiogenIdec; Celgene (BMS); EMD Inc; Sanofi-Genzyme; Hoffman La-Roche; Merck Serono; Novartis; Teva Canada Innovation­. Received research or educational grants from: Sanofi-Genzyme Canada; Hoffman-La Roche; EMD Inc.

A shift in managing symptoms for patients with relapsing-remitting multiple sclerosis (RRMS) may be in order as new research questions the efficacy of three commonly used drugs for MS-related fatigue. Results of a study from Johns Hopkins University show that amantadine, modafinil, and methylphenidate were not superior to placebo. As Dr Mark Freedman reports in this ReCAP, the study suggests that clinicians consider focusing more on patient sleep quality rather than tiredness in their evaluation of fatigue.

This study was presented during the 8th Joint Meeting of ACTRIMS-ECTRIMS, this year branded MSVirtual2020. Dr Freedman, a recognized neurologist from the University of Ottawa, shares key highlights from the online conference.

He explains the significance of new evidence that points to the potential for a selective retinoid X receptor agonist to promote remyelination in relapsing disease. He also discusses a study by researchers at the University of Melbourne that looked at data from the largest cohort of MS patients with COVID-19 and drew troubling conclusions.

Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; Director, Multiple Sclerosis Research Unit, The Ottawa Hospital – General Campus, Ottawa, Ontario, Canada.

Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships: Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson & Johnson); Alexion; Atara Biotherapeutics; BayerHealthcare; BiogenIdec; Celgene; Clene Nanomedicine; GRI Bio; Hoffman La-Roche; Magenta Therapeutics; Merck Serono; MedDay; Novartis; Sanofi-Genzyme; Teva Canada Innovation. Serve(d) as a member of a speakers bureau for: Sanofi-Genzyme; EMD Serono. Received honoraria or consultation fees for: Actelion (Janssen/Johnson & Johnson); Alexion; BiogenIdec; Celgene (BMS); EMD Inc; Sanofi-Genzyme; Hoffman La-Roche; Merck Serono; Novartis; Teva Canada Innovation­. Received research or educational grants from: Sanofi-Genzyme Canada; Hoffman-La Roche; EMD Inc.

In relapsing-remitting multiple sclerosis (RRMS), MRI has provided a key indication of disease presence and activity. With the availability of serum neurofilament (sNfL) assays, disease activity can be correlated with sNfL levels.

Dr Tobias Derfuss, from University Hospital Basel in Basel, Switzerland, discusses emerging research reported at the ACTRIMS/ECTRIMS 2020 Virtual Meeting, focusing on the use of sNfL as a biomarker for monitoring treatment response and disease activity in RRMS.

Dr Derfuss highlights one study in which longitudinal observations showed that high levels of sNfL at baseline are associated with a high risk for gadolinium-enhancing lesions; the study authors suggest that quarterly monitoring may be adequate for surveillance of subclinical disease.

In another study, higher sNfL levels at baseline were linked to a higher risk for T2 lesions and a more pronounced brain atrophy rate, but disability progression was not correlated to baseline sNfL levels.

Finally, Dr Derfuss reports on a real-world, large cohort study supporting the value of sNfL to capture and predict disability progression independent of relapses.

Tobias J. Derfuss, MD, Professor, Head of Outpatient Clinic, Department of Neurology, University Hospital Board, Basel, Switzerland

Tobias J. Derfuss, MD, has disclosed the following relevant financial relationships:­ Received financial compensation for his activities in advisory boards, steering committees, data safety monitoring boards, and consultation for: Novartis; Merck; Biogen; Celgene; Actelion; Mitsubishi Pharma; MedDay; Roche; Sanofi Genzyme. Received research grant from: Novartis; Biogen; Roche; Swiss National Science Foundation; European Union; Swiss MS Society. Spouse is an employee of and holds stock options in: Novartis

In relapsing-remitting multiple sclerosis (RRMS), MRI has provided a key indication of disease presence and activity. With the availability of serum neurofilament (sNfL) assays, disease activity can be correlated with sNfL levels.

Dr Tobias Derfuss, from University Hospital Basel in Basel, Switzerland, discusses emerging research reported at the ACTRIMS/ECTRIMS 2020 Virtual Meeting, focusing on the use of sNfL as a biomarker for monitoring treatment response and disease activity in RRMS.

Dr Derfuss highlights one study in which longitudinal observations showed that high levels of sNfL at baseline are associated with a high risk for gadolinium-enhancing lesions; the study authors suggest that quarterly monitoring may be adequate for surveillance of subclinical disease.

In another study, higher sNfL levels at baseline were linked to a higher risk for T2 lesions and a more pronounced brain atrophy rate, but disability progression was not correlated to baseline sNfL levels.

Finally, Dr Derfuss reports on a real-world, large cohort study supporting the value of sNfL to capture and predict disability progression independent of relapses.

Tobias J. Derfuss, MD, Professor, Head of Outpatient Clinic, Department of Neurology, University Hospital Board, Basel, Switzerland

Tobias J. Derfuss, MD, has disclosed the following relevant financial relationships:­ Received financial compensation for his activities in advisory boards, steering committees, data safety monitoring boards, and consultation for: Novartis; Merck; Biogen; Celgene; Actelion; Mitsubishi Pharma; MedDay; Roche; Sanofi Genzyme. Received research grant from: Novartis; Biogen; Roche; Swiss National Science Foundation; European Union; Swiss MS Society. Spouse is an employee of and holds stock options in: Novartis

In relapsing-remitting multiple sclerosis (RRMS), MRI has provided a key indication of disease presence and activity. With the availability of serum neurofilament (sNfL) assays, disease activity can be correlated with sNfL levels.

Dr Tobias Derfuss, from University Hospital Basel in Basel, Switzerland, discusses emerging research reported at the ACTRIMS/ECTRIMS 2020 Virtual Meeting, focusing on the use of sNfL as a biomarker for monitoring treatment response and disease activity in RRMS.

Dr Derfuss highlights one study in which longitudinal observations showed that high levels of sNfL at baseline are associated with a high risk for gadolinium-enhancing lesions; the study authors suggest that quarterly monitoring may be adequate for surveillance of subclinical disease.

In another study, higher sNfL levels at baseline were linked to a higher risk for T2 lesions and a more pronounced brain atrophy rate, but disability progression was not correlated to baseline sNfL levels.

Finally, Dr Derfuss reports on a real-world, large cohort study supporting the value of sNfL to capture and predict disability progression independent of relapses.

Tobias J. Derfuss, MD, Professor, Head of Outpatient Clinic, Department of Neurology, University Hospital Board, Basel, Switzerland

Tobias J. Derfuss, MD, has disclosed the following relevant financial relationships:­ Received financial compensation for his activities in advisory boards, steering committees, data safety monitoring boards, and consultation for: Novartis; Merck; Biogen; Celgene; Actelion; Mitsubishi Pharma; MedDay; Roche; Sanofi Genzyme. Received research grant from: Novartis; Biogen; Roche; Swiss National Science Foundation; European Union; Swiss MS Society. Spouse is an employee of and holds stock options in: Novartis

Key clinical point: Increased high-density lipoprotein cholesterol (HDL-C) is associated with decreased gray matter and cortical atrophy in patients with multiple sclerosis (MS) after adjusting for baseline serum neurofilaments (sNfL).

Major finding: Gray matter volume and cortical volume had significant associations with percent change in HDL-C (P = .0024 and P less than .001, respectively) after adjusting for sNfL as a predictor.

Study details: This prospective longitudinal study assessed patients with relapsing-remitting MS (n = 75) and progressive multiple sclerosis (n = 37) over a 5-year follow-up period.

Disclosures: The study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health. B Weinstock-Guttman, J Kuhle, R Zivadinov and M Ramanathan reported ties with multiple pharmaceutical companies. The remaining authors declared no conflicts of interest.

Citation: McComb M et al. Mult Scler Relat Disord. 2020 Jul 11. doi: 10.1016/j.msard.2020.102389.

Key clinical point: Increased high-density lipoprotein cholesterol (HDL-C) is associated with decreased gray matter and cortical atrophy in patients with multiple sclerosis (MS) after adjusting for baseline serum neurofilaments (sNfL).

Major finding: Gray matter volume and cortical volume had significant associations with percent change in HDL-C (P = .0024 and P less than .001, respectively) after adjusting for sNfL as a predictor.

Study details: This prospective longitudinal study assessed patients with relapsing-remitting MS (n = 75) and progressive multiple sclerosis (n = 37) over a 5-year follow-up period.

Disclosures: The study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health. B Weinstock-Guttman, J Kuhle, R Zivadinov and M Ramanathan reported ties with multiple pharmaceutical companies. The remaining authors declared no conflicts of interest.

Citation: McComb M et al. Mult Scler Relat Disord. 2020 Jul 11. doi: 10.1016/j.msard.2020.102389.

Key clinical point: Increased high-density lipoprotein cholesterol (HDL-C) is associated with decreased gray matter and cortical atrophy in patients with multiple sclerosis (MS) after adjusting for baseline serum neurofilaments (sNfL).

Major finding: Gray matter volume and cortical volume had significant associations with percent change in HDL-C (P = .0024 and P less than .001, respectively) after adjusting for sNfL as a predictor.

Study details: This prospective longitudinal study assessed patients with relapsing-remitting MS (n = 75) and progressive multiple sclerosis (n = 37) over a 5-year follow-up period.

Disclosures: The study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health. B Weinstock-Guttman, J Kuhle, R Zivadinov and M Ramanathan reported ties with multiple pharmaceutical companies. The remaining authors declared no conflicts of interest.

Citation: McComb M et al. Mult Scler Relat Disord. 2020 Jul 11. doi: 10.1016/j.msard.2020.102389.

Key clinical point: Early and continuous ocrelizumab treatment can provide sustained benefit on clinical and magnetic resonance imaging measures for disease progression in patients with relapsing multiple sclerosis (MS).

Major finding: At 5 years, the cumulative proportion of patients with 24-week confirmed disability progression was lower among those who continued ocrelizumab vs those who switched from interferon (IFN) β-1a to ocrelizumab (16.1% vs 21.3%; P = .014). Similarly, brain atrophy was significantly lower among those who continued ocrelizumab than in those who switched to ocrelizumab (P less than .01).

Study details: The OPERA open label extension study evaluated long-term efficacy and safety (5 years follow-up) of ocrelizumab (600 mg) in adults with relapsing MS. Patients previously assigned to INF β-1a  (n = 829) and ocrelizumab (n = 827) entered the open-label extension phase in this study, of which 623 switched to ocrelizumab and 702 continued ocrelizumab, respectively

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland. The lead author reporting receiving travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations. Some of his coinvestigators reported owning stock in, being an employee of, receiving support from, and/or serving on scientific advisory board for F. Hoffmann-La Roche Ltd.

Citation: Hauser SL et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000010376.

Key clinical point: Early and continuous ocrelizumab treatment can provide sustained benefit on clinical and magnetic resonance imaging measures for disease progression in patients with relapsing multiple sclerosis (MS).

Major finding: At 5 years, the cumulative proportion of patients with 24-week confirmed disability progression was lower among those who continued ocrelizumab vs those who switched from interferon (IFN) β-1a to ocrelizumab (16.1% vs 21.3%; P = .014). Similarly, brain atrophy was significantly lower among those who continued ocrelizumab than in those who switched to ocrelizumab (P less than .01).

Study details: The OPERA open label extension study evaluated long-term efficacy and safety (5 years follow-up) of ocrelizumab (600 mg) in adults with relapsing MS. Patients previously assigned to INF β-1a  (n = 829) and ocrelizumab (n = 827) entered the open-label extension phase in this study, of which 623 switched to ocrelizumab and 702 continued ocrelizumab, respectively

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland. The lead author reporting receiving travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations. Some of his coinvestigators reported owning stock in, being an employee of, receiving support from, and/or serving on scientific advisory board for F. Hoffmann-La Roche Ltd.

Citation: Hauser SL et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000010376.

Key clinical point: Early and continuous ocrelizumab treatment can provide sustained benefit on clinical and magnetic resonance imaging measures for disease progression in patients with relapsing multiple sclerosis (MS).

Major finding: At 5 years, the cumulative proportion of patients with 24-week confirmed disability progression was lower among those who continued ocrelizumab vs those who switched from interferon (IFN) β-1a to ocrelizumab (16.1% vs 21.3%; P = .014). Similarly, brain atrophy was significantly lower among those who continued ocrelizumab than in those who switched to ocrelizumab (P less than .01).

Study details: The OPERA open label extension study evaluated long-term efficacy and safety (5 years follow-up) of ocrelizumab (600 mg) in adults with relapsing MS. Patients previously assigned to INF β-1a  (n = 829) and ocrelizumab (n = 827) entered the open-label extension phase in this study, of which 623 switched to ocrelizumab and 702 continued ocrelizumab, respectively

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland. The lead author reporting receiving travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations. Some of his coinvestigators reported owning stock in, being an employee of, receiving support from, and/or serving on scientific advisory board for F. Hoffmann-La Roche Ltd.

Citation: Hauser SL et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000010376.

Key clinical point: Real-world data demonstrates effectiveness of rituximab in reducing disease activity and maintaining long-term treatment in patients with multiple sclerosis (MS).

Major finding: The odds for experiencing a clinical relapse, contrast-enhancing lesions (CEL), and/or new T2 lesions were greater with fingolimod  (adjusted odds ratio [aOR], 3.17; P less than .001)  and dimethyl fumarate (aOR, 2.68; P less than .001) compared with rituximab. Similarly, natalizimab vs rituximab showed higher odds for disease activity (aOR, 1.36; P = 0.216). The odds for discontinuation were higher for fingolimod (aOR, 2.02; P = .005) and dimethyl fumarate (aOR, 3.27; P less than .001) compared with rituximab.

Study details: A retrospective real-world study included MS patients who were initiated on rituximab (n = 182), natalizumab (n = 451), fingolimod (n = 271) or dimethyl fumarate (n = 342) and followed for 2 years.

Disclosures: This study received no funding. KV Nair, JR Corboy, T Vollmer and E Alvarez reported relationships with multiple pharmaceutical companies.

Citation: Vollmer BL et al. Ann Clin Transl Neurol. 2020 Aug 6. doi: 10.1002/acn3.51111.

Key clinical point: Real-world data demonstrates effectiveness of rituximab in reducing disease activity and maintaining long-term treatment in patients with multiple sclerosis (MS).

Major finding: The odds for experiencing a clinical relapse, contrast-enhancing lesions (CEL), and/or new T2 lesions were greater with fingolimod  (adjusted odds ratio [aOR], 3.17; P less than .001)  and dimethyl fumarate (aOR, 2.68; P less than .001) compared with rituximab. Similarly, natalizimab vs rituximab showed higher odds for disease activity (aOR, 1.36; P = 0.216). The odds for discontinuation were higher for fingolimod (aOR, 2.02; P = .005) and dimethyl fumarate (aOR, 3.27; P less than .001) compared with rituximab.

Study details: A retrospective real-world study included MS patients who were initiated on rituximab (n = 182), natalizumab (n = 451), fingolimod (n = 271) or dimethyl fumarate (n = 342) and followed for 2 years.

Disclosures: This study received no funding. KV Nair, JR Corboy, T Vollmer and E Alvarez reported relationships with multiple pharmaceutical companies.

Citation: Vollmer BL et al. Ann Clin Transl Neurol. 2020 Aug 6. doi: 10.1002/acn3.51111.

Key clinical point: Real-world data demonstrates effectiveness of rituximab in reducing disease activity and maintaining long-term treatment in patients with multiple sclerosis (MS).

Major finding: The odds for experiencing a clinical relapse, contrast-enhancing lesions (CEL), and/or new T2 lesions were greater with fingolimod  (adjusted odds ratio [aOR], 3.17; P less than .001)  and dimethyl fumarate (aOR, 2.68; P less than .001) compared with rituximab. Similarly, natalizimab vs rituximab showed higher odds for disease activity (aOR, 1.36; P = 0.216). The odds for discontinuation were higher for fingolimod (aOR, 2.02; P = .005) and dimethyl fumarate (aOR, 3.27; P less than .001) compared with rituximab.

Study details: A retrospective real-world study included MS patients who were initiated on rituximab (n = 182), natalizumab (n = 451), fingolimod (n = 271) or dimethyl fumarate (n = 342) and followed for 2 years.

Disclosures: This study received no funding. KV Nair, JR Corboy, T Vollmer and E Alvarez reported relationships with multiple pharmaceutical companies.

Citation: Vollmer BL et al. Ann Clin Transl Neurol. 2020 Aug 6. doi: 10.1002/acn3.51111.

Key clinical point: Elevated blood lipid parameters in patients with multiple sclerosis (MS) may harm cognitive functions.

Major finding: A negative correlation was observed between cholesterol and general cognitive functioning score after rehabilitation and the Expanded Disability Status Scale scores (Cronbach alpha, 0.60 and 0.65, respectively). Triglyceride scores also has a negative correlation with working memory scores before and after rehabilitation (Cronbach alpha, 0.36 and 0.40, respectively). Furthermore, body mass index scores had a negative correlation with the visuospatial ability (Cronbach alpha, 0.59)

Study details: The study included 90 inpatients with relapsing remitting, primary and secondary progressive MS who underwent intense neurorehabilitation training.

Disclosures: The study received no funding. The authors reported no conflicts of interest.

Citation: Andaloro A et al. Int J Neurosci. 2020 Aug 7. doi: 10.1080/00207454.2020.1807980.

Key clinical point: Elevated blood lipid parameters in patients with multiple sclerosis (MS) may harm cognitive functions.

Major finding: A negative correlation was observed between cholesterol and general cognitive functioning score after rehabilitation and the Expanded Disability Status Scale scores (Cronbach alpha, 0.60 and 0.65, respectively). Triglyceride scores also has a negative correlation with working memory scores before and after rehabilitation (Cronbach alpha, 0.36 and 0.40, respectively). Furthermore, body mass index scores had a negative correlation with the visuospatial ability (Cronbach alpha, 0.59)

Study details: The study included 90 inpatients with relapsing remitting, primary and secondary progressive MS who underwent intense neurorehabilitation training.

Disclosures: The study received no funding. The authors reported no conflicts of interest.

Citation: Andaloro A et al. Int J Neurosci. 2020 Aug 7. doi: 10.1080/00207454.2020.1807980.

Key clinical point: Elevated blood lipid parameters in patients with multiple sclerosis (MS) may harm cognitive functions.

Major finding: A negative correlation was observed between cholesterol and general cognitive functioning score after rehabilitation and the Expanded Disability Status Scale scores (Cronbach alpha, 0.60 and 0.65, respectively). Triglyceride scores also has a negative correlation with working memory scores before and after rehabilitation (Cronbach alpha, 0.36 and 0.40, respectively). Furthermore, body mass index scores had a negative correlation with the visuospatial ability (Cronbach alpha, 0.59)

Study details: The study included 90 inpatients with relapsing remitting, primary and secondary progressive MS who underwent intense neurorehabilitation training.

Disclosures: The study received no funding. The authors reported no conflicts of interest.

Citation: Andaloro A et al. Int J Neurosci. 2020 Aug 7. doi: 10.1080/00207454.2020.1807980.

In patients with pediatric-onset multiple sclerosis (MS), increased abundance of Blautia stercoris and its variants in the gut is associated with an increased risk of relapse. No broad differences in gut bacterial composition, however, are associated with risk of relapse, according to the investigators. The findings were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.

Previous research has found an association between Blautia stercoris and disease activity in other immune-mediated diseases such as systemic lupus. Although the current study is the largest in patients with MS that includes data about the microbiome and relapses, its findings require replication, said Mary Horton, a doctoral candidate in epidemiology at the University of California, Berkeley.

Gut microbes digest food, produce vitamins (for example, B12 and K), create a barrier against pathogens, and regulate the immune system, among other tasks. Most current knowledge about the gut microbiome in MS comes from studies of patients with adult-onset MS. In 2016, Tremlett et al. found an increase in Desulfovibrionaceae and a decrease in Lachnospiraceae and Ruminococcaceae in patients with pediatric-onset MS. They also found that a decrease in Fusobacteria was associated with risk of relapse in this population.
 

Advanced analytical methods

Using a larger sample size and newer analytical methods than in the study by Tremlett and colleagues, Ms. Horton’s group sought to determine whether features of the gut microbiome are associated with relapse. From 2014 to 2018, the investigators recruited 53 patients with pediatric-onset MS from the University of California, San Francisco, and six centers in the U.S. Network of Pediatric MS Centers. At baseline, they collected stool samples, blood samples, information about past relapses, medication records, demographics, and environmental factors. At each relapse, the investigators collected information about the patient’s current and past medication use and about relapses that the patient had had since the previous visit.

Ms. Horton and colleagues analyzed the stool samples using 16S rRNA sequencing of the V4 region. They identified amplicon sequence variants (ASVs), which are used to define species of bacteria, with the Divisive Amplicon Denoising Algorithm-2 (DADA2). Taxonomies were assigned using the naive Bayesian classifier method, and the read count was normalized using multiple rarefaction.

The investigators identified ASV clusters using weighted genetic correlation network analysis (WGCNA). To evaluate whether individual ASVs were associated with relapse, they used a Prentice, Williams, and Peterson (PWP) recurrent event model, an extension of the Cox proportional hazards model.
 

The role of methanogenesis

Ms. Horton and colleagues included 53 patients (72% girls) in their study. The population’s mean age was 14.3 years at disease onset and 15.5 years at stool sample collection. About 70% of patients were White, and about 36% were Hispanic. Mean disease duration was 1.3 years, and median Expanded Disability Status Scale score was 1.0.

Approximately 45% of participants had one relapse, and 30% had more than one relapse during the subsequent mean follow-up of 2.5 years. About 91% of patients used a disease-modifying therapy during follow-up.

Gut bacterial abundance was broadly similar between patients who relapsed during the study period and those who did not. Of 270 ASVs included in the analyses, 20 were nominally associated with risk of relapse. Blautia stercoris had the most significant association with relapse risk (hazard ratio, 2.50). Blautia massiliensis also was among the 20 ASVs associated with risk of relapse.

WGCNA identified six ASV clusters. Higher values of one cluster’s eigengene were significantly associated with higher relapse risk (HR, 1.23). The following four ASVs nominally associated with higher relapse risk were in this cluster: Blautia massiliensis, Dorea longicatena, Coprococcus comes, and an unknown species in genus Subdoligranulum.

When Ms. Horton and colleagues examined the pathways from these bacterial species, they found 10 that were significantly associated with the risk of relapse. Four of these 10 pathways are involved in methane production, which suggests the involvement of methanogenesis pathways in relapse.

Although the investigators used advanced techniques for genetic and statistical analysis, the study’s sample size is small, Ms. Horton acknowledged. In addition, the conclusions that can be drawn from observational data are limited.

These suggest several avenues for future research. “There is a big question about how the different treatments that people are on when they are experiencing relapses might impact the microbiome,” said Ms. Horton. “Is the microbiome impacting your treatment response, or is it the reverse?” Investigators also could examine why the methane production pathway is overrepresented among people with MS who have relapses. “Which specific archaea might be leading to that increase in methane is a ripe future study question. Just what that means for health is really unknown.”

The National MS Society and the National Institute of Neurological Disorders and Stroke provided funding for the study. Ms. Horton had no disclosures.

[email protected]

SOURCE: Horton M et al. MSVirtual2020, Abstract LB01.05.

In patients with pediatric-onset multiple sclerosis (MS), increased abundance of Blautia stercoris and its variants in the gut is associated with an increased risk of relapse. No broad differences in gut bacterial composition, however, are associated with risk of relapse, according to the investigators. The findings were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.

Previous research has found an association between Blautia stercoris and disease activity in other immune-mediated diseases such as systemic lupus. Although the current study is the largest in patients with MS that includes data about the microbiome and relapses, its findings require replication, said Mary Horton, a doctoral candidate in epidemiology at the University of California, Berkeley.

Gut microbes digest food, produce vitamins (for example, B12 and K), create a barrier against pathogens, and regulate the immune system, among other tasks. Most current knowledge about the gut microbiome in MS comes from studies of patients with adult-onset MS. In 2016, Tremlett et al. found an increase in Desulfovibrionaceae and a decrease in Lachnospiraceae and Ruminococcaceae in patients with pediatric-onset MS. They also found that a decrease in Fusobacteria was associated with risk of relapse in this population.
 

Advanced analytical methods

Using a larger sample size and newer analytical methods than in the study by Tremlett and colleagues, Ms. Horton’s group sought to determine whether features of the gut microbiome are associated with relapse. From 2014 to 2018, the investigators recruited 53 patients with pediatric-onset MS from the University of California, San Francisco, and six centers in the U.S. Network of Pediatric MS Centers. At baseline, they collected stool samples, blood samples, information about past relapses, medication records, demographics, and environmental factors. At each relapse, the investigators collected information about the patient’s current and past medication use and about relapses that the patient had had since the previous visit.

Ms. Horton and colleagues analyzed the stool samples using 16S rRNA sequencing of the V4 region. They identified amplicon sequence variants (ASVs), which are used to define species of bacteria, with the Divisive Amplicon Denoising Algorithm-2 (DADA2). Taxonomies were assigned using the naive Bayesian classifier method, and the read count was normalized using multiple rarefaction.

The investigators identified ASV clusters using weighted genetic correlation network analysis (WGCNA). To evaluate whether individual ASVs were associated with relapse, they used a Prentice, Williams, and Peterson (PWP) recurrent event model, an extension of the Cox proportional hazards model.
 

The role of methanogenesis

Ms. Horton and colleagues included 53 patients (72% girls) in their study. The population’s mean age was 14.3 years at disease onset and 15.5 years at stool sample collection. About 70% of patients were White, and about 36% were Hispanic. Mean disease duration was 1.3 years, and median Expanded Disability Status Scale score was 1.0.

Approximately 45% of participants had one relapse, and 30% had more than one relapse during the subsequent mean follow-up of 2.5 years. About 91% of patients used a disease-modifying therapy during follow-up.

Gut bacterial abundance was broadly similar between patients who relapsed during the study period and those who did not. Of 270 ASVs included in the analyses, 20 were nominally associated with risk of relapse. Blautia stercoris had the most significant association with relapse risk (hazard ratio, 2.50). Blautia massiliensis also was among the 20 ASVs associated with risk of relapse.

WGCNA identified six ASV clusters. Higher values of one cluster’s eigengene were significantly associated with higher relapse risk (HR, 1.23). The following four ASVs nominally associated with higher relapse risk were in this cluster: Blautia massiliensis, Dorea longicatena, Coprococcus comes, and an unknown species in genus Subdoligranulum.

When Ms. Horton and colleagues examined the pathways from these bacterial species, they found 10 that were significantly associated with the risk of relapse. Four of these 10 pathways are involved in methane production, which suggests the involvement of methanogenesis pathways in relapse.

Although the investigators used advanced techniques for genetic and statistical analysis, the study’s sample size is small, Ms. Horton acknowledged. In addition, the conclusions that can be drawn from observational data are limited.

These suggest several avenues for future research. “There is a big question about how the different treatments that people are on when they are experiencing relapses might impact the microbiome,” said Ms. Horton. “Is the microbiome impacting your treatment response, or is it the reverse?” Investigators also could examine why the methane production pathway is overrepresented among people with MS who have relapses. “Which specific archaea might be leading to that increase in methane is a ripe future study question. Just what that means for health is really unknown.”

The National MS Society and the National Institute of Neurological Disorders and Stroke provided funding for the study. Ms. Horton had no disclosures.

[email protected]

SOURCE: Horton M et al. MSVirtual2020, Abstract LB01.05.

In patients with pediatric-onset multiple sclerosis (MS), increased abundance of Blautia stercoris and its variants in the gut is associated with an increased risk of relapse. No broad differences in gut bacterial composition, however, are associated with risk of relapse, according to the investigators. The findings were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.

Previous research has found an association between Blautia stercoris and disease activity in other immune-mediated diseases such as systemic lupus. Although the current study is the largest in patients with MS that includes data about the microbiome and relapses, its findings require replication, said Mary Horton, a doctoral candidate in epidemiology at the University of California, Berkeley.

Gut microbes digest food, produce vitamins (for example, B12 and K), create a barrier against pathogens, and regulate the immune system, among other tasks. Most current knowledge about the gut microbiome in MS comes from studies of patients with adult-onset MS. In 2016, Tremlett et al. found an increase in Desulfovibrionaceae and a decrease in Lachnospiraceae and Ruminococcaceae in patients with pediatric-onset MS. They also found that a decrease in Fusobacteria was associated with risk of relapse in this population.
 

Advanced analytical methods

Using a larger sample size and newer analytical methods than in the study by Tremlett and colleagues, Ms. Horton’s group sought to determine whether features of the gut microbiome are associated with relapse. From 2014 to 2018, the investigators recruited 53 patients with pediatric-onset MS from the University of California, San Francisco, and six centers in the U.S. Network of Pediatric MS Centers. At baseline, they collected stool samples, blood samples, information about past relapses, medication records, demographics, and environmental factors. At each relapse, the investigators collected information about the patient’s current and past medication use and about relapses that the patient had had since the previous visit.

Ms. Horton and colleagues analyzed the stool samples using 16S rRNA sequencing of the V4 region. They identified amplicon sequence variants (ASVs), which are used to define species of bacteria, with the Divisive Amplicon Denoising Algorithm-2 (DADA2). Taxonomies were assigned using the naive Bayesian classifier method, and the read count was normalized using multiple rarefaction.

The investigators identified ASV clusters using weighted genetic correlation network analysis (WGCNA). To evaluate whether individual ASVs were associated with relapse, they used a Prentice, Williams, and Peterson (PWP) recurrent event model, an extension of the Cox proportional hazards model.
 

The role of methanogenesis

Ms. Horton and colleagues included 53 patients (72% girls) in their study. The population’s mean age was 14.3 years at disease onset and 15.5 years at stool sample collection. About 70% of patients were White, and about 36% were Hispanic. Mean disease duration was 1.3 years, and median Expanded Disability Status Scale score was 1.0.

Approximately 45% of participants had one relapse, and 30% had more than one relapse during the subsequent mean follow-up of 2.5 years. About 91% of patients used a disease-modifying therapy during follow-up.

Gut bacterial abundance was broadly similar between patients who relapsed during the study period and those who did not. Of 270 ASVs included in the analyses, 20 were nominally associated with risk of relapse. Blautia stercoris had the most significant association with relapse risk (hazard ratio, 2.50). Blautia massiliensis also was among the 20 ASVs associated with risk of relapse.

WGCNA identified six ASV clusters. Higher values of one cluster’s eigengene were significantly associated with higher relapse risk (HR, 1.23). The following four ASVs nominally associated with higher relapse risk were in this cluster: Blautia massiliensis, Dorea longicatena, Coprococcus comes, and an unknown species in genus Subdoligranulum.

When Ms. Horton and colleagues examined the pathways from these bacterial species, they found 10 that were significantly associated with the risk of relapse. Four of these 10 pathways are involved in methane production, which suggests the involvement of methanogenesis pathways in relapse.

Although the investigators used advanced techniques for genetic and statistical analysis, the study’s sample size is small, Ms. Horton acknowledged. In addition, the conclusions that can be drawn from observational data are limited.

These suggest several avenues for future research. “There is a big question about how the different treatments that people are on when they are experiencing relapses might impact the microbiome,” said Ms. Horton. “Is the microbiome impacting your treatment response, or is it the reverse?” Investigators also could examine why the methane production pathway is overrepresented among people with MS who have relapses. “Which specific archaea might be leading to that increase in methane is a ripe future study question. Just what that means for health is really unknown.”

The National MS Society and the National Institute of Neurological Disorders and Stroke provided funding for the study. Ms. Horton had no disclosures.

[email protected]

SOURCE: Horton M et al. MSVirtual2020, Abstract LB01.05.

The risk of severe outcomes from COVID-19 infection in patients with multiple sclerosis (MS) seems to align with that seen in the general population, new U.S. data suggest. A separate study from the United Kingdom also found similar trends of rates of COVID-19 infection in patients with MS and the general population.

Both studies were presented Sept. 26 at a special session on multiple sclerosis and COVID-19 at a final “Encore” event as part of the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The U.S. data appear consistent with studies from several other countries, in that worse COVID-19 outcomes increase with age and higher disability levels, both of which would be expected from findings in the general population.

The U.S. data also show a clear effect of race in MS, with higher rates of adverse COVID-19 outcomes in Black patients, again in line with what is seen in the general population.

“I would say the results from our study and in general do not suggest that MS itself is associated with higher risks of severe COVID-19 outcomes, compared with the general population,” said Amber Salter, PhD.

Dr. Salter, who is assistant professor of biostatistics at Washington University, St. Louis, presented data from the COViMS North American registry, set up for health care providers to report persons with MS who are infected with COVID-19.

The COViMS registry so far has information on 858 patients with MS who have COVID-19 (80% verified by a positive test), as reported from 150 different health care providers in the United States and Canada. The average age was 48 years, with average disease duration of 13.6 years. MS clinical course was reported as relapsing remitting in 78%, secondary progressive in 15%, and primary progressive in 5%. Most patients (72%) were fully ambulatory, 16% could walk with assistance, and 12% were nonambulatory.

Severe COVID-19 outcomes were classified as mortality (which occurred in 5.7% of the cohort), mortality/ICU admission (13.6%) and mortality/ICU admission/hospitalization (30.2%).

Results were adjusted for many different covariates, including sex, age, smoking, MS clinical course (relapsing, progressive), disease duration, ambulation, individual comorbidities (cardiovascular disease, cerebrovascular disease, chronic kidney disease, chronic lung disease, diabetes, hypertension, morbid obesity), and disease-modifying therapy use.

In multivariable logistic regression analyses, older age, having chronic renal disease, and being nonambulatory were consistently associated with increased odds of poorer outcomes. Chronic kidney disease had the strongest association with mortality (odds ratio, 28.6; P < .001). Other factors associated with mortality included cardiovascular disease (OR, 4.35; P = .009); age (OR per 10 years, 1.91; P = .012), and male sex (OR, 2.60; P = .041).

Patients who were nonambulatory had a higher risk of mortality/ICU admission/hospitalization (OR, 3.32; P = .003). This endpoint was also increased in patients on anti-CD20 drugs, compared with other disease-modifying treatment (OR, 2.31; P = .002), consistent with results from at least two other studies.

Disease-modifying therapy in general was not associated with an increased risk of worse outcomes. “There was some concern at the outset about the effect of disease-modifying therapies on COVID-19 outcomes, but most studies have not found an increased risk of worse outcomes in patients on such drug treatments, with the possible exception of anti-CD20 drugs,” Dr. Salter said.

“Some disease-modifying therapies may actually be protective (particularly interferon) and studies are investigating whether they may have a role in the treatment of COVID-19,” she added.

“The factors in MS patients that we and others have found to be associated with worse COVID-19 outcomes may not be specific to MS. Older age is known to be a primary risk factor for worse COVID-19 outcomes in the general population, and increasing disability presumably tracks with worse general heath,” Dr. Salter commented.

“I would say the overall data are fairly reassuring for MS patents,” she concluded.
 

Black patients have higher risk

One worrying finding in the North American data, however, was the effect of race. “We found an independent effect of race for worse COVID-19 outcomes in MS patients,” Dr. Slater said.

Of the 858 patients in the COViMS registry, 65.7% were White and 26.1% were Black. Black individuals were more likely to be younger, never smokers, have shorter MS duration, a relapsing MS course, and have comorbidities, compared with White patients. A higher proportion of Black patients had hypertension (40.2% vs 19.5%) and morbid obesity (17% vs. 9.5%).

Results showed that mortality rates were not statistically different between White and Black patients, but Black race was associated with increased risk of mortality and/or ICU admission, compared with White patients (16.9% vs. 12.8%), and multivariate logistic regression analysis showed Black race was independently associated with mortality/ICU admission after adjustments for covariates (OR, 3.7; P = .002).

Black race was also associated with increased risk of mortality/ICU admission/hospital admission (35.8% vs. 30.2%), and after adjustment for covariates this was found to be an independent predictor (OR, 1.7; P = .04).

“This higher COVID-19 risk in Black individuals is also seen in the general population, so these results are not that surprising and it doesn’t appear to be an effect specific to MS patients,” Dr. Salter commented.
 

U.K. data on risk of contracting COVID-19 

A U.K. study also suggested race to be an independent predictor in the risk of contracting COVID-19 in patients with MS.

The study of more than 5,000 patients with MS showed that those from a Black, Asian, and Minority Ethnic group were twice as likely to report having COVID-19 than those who were White.

The study, which was conducted during the U.K. lockdown, also found that the trend of COVID-19 infection in patients with MS is comparable with that of the U.K. general population.

Presenting the data, Afagh Garjani, MD, concluded: “During a period with strict physical distancing measures, patients with MS are not at an increased risk of contracting COVID-19.”

Dr. Garjani, a neurology clinical research fellow at the University of Nottingham, (England), explained that the COVID-19 pandemic has introduced uncertainties into the MS community, and the focus so far has been the severity of infection among people with MS who have COVID-19.

“This approach has left questions about the risk of contracting disease in people with MS unanswered, which has implications as society gradually returns to normal,” she said.

Dr. Garjani presented data from the United Kingdom MS Register (UKMSR), which has been collecting demographic and MS-related data since 2011 from patients with MS throughout the United Kingdom.

On March 17 – just before the lockdown in United Kingdom – existing participants of the UKMSR were asked to join the COVID-19 study. The study was also advertised through social media. In this ongoing study, people with MS answered a COVID-19–related survey at participation and a different follow-up survey every 2 weeks depending on whether they contracted COVID-19.

The COVID-19 study included 5,309 patients with MS. The mean age of the study population was 52.4 years, 76.1% were female, and 95.7% were White. Of the 5,309 patients, 535 (10%) reported a self-diagnosis of COVID-19. Because of limited availability of tests in the United Kingdom at the time, only 75 patents had a positive polymerase chain reaction result.

“To our knowledge, this is the largest community-based study of COVID-19 in patients with MS worldwide,” Dr. Garjani said. She presented results from the period March 23 to June 24, when the United Kingdom was in a period of lockdown with vulnerable groups encouraged to self-isolate completely.

In this MS cohort, 47% reported self-isolating at some point. Those at older age and higher Expanded Disability Status Scale (EDSS) score were more likely to have self-isolated.

The researchers did not find that patients with progressive MS or those on disease-modifying therapies in general isolated more, but patients on monoclonal antibody drugs and fingolimod were more likely to self-isolate versus those on other therapies. “This may be because there are concerns about infection with these drugs and patients on these therapies may be more concerned about contracting COVID-19,” Dr. Garjani suggested.

In terms of contracting COVID, the researchers found a reduced risk of COVID-19 (self-diagnosed) in patients with older age and higher EDSS. “This is not really surprising that these patients were more likely to self-isolate,” Dr. Garjani commented.

No association was seen between type of MS, disease duration, disease-modifying therapy in general, and risk of COVID-19. No individual drug treatment increased risk versus no therapy or versus self-injectables. But there was an increased risk of contracting the virus in patients whose race was Black, Asian, or Minority Ethnic (OR, 2.2), which is in line with findings from the general population.

“This study is unique – the denominator is all people with MS. We are looking primarily at the risk of contracting COVID-19. Other studies are focusing more on people with MS who have COVID and assessing risk of a severe COVID outcome. Our results are not contradicting the findings from those studies,” Dr. Garjani said.

The results were similar only when patients with a confirmed COVID-19 test were considered.

In terms of outcomes in those who reported COVID-19 infection, preliminary results have not shown any MS factors – such as EDSS, age, type of MS, drug therapy in general – to be associated with outcome.

“Since the COVID-19 outbreak started there has been concern among MS patients, especially among those on disease-modifying therapies, about whether they are at increased risk of infection and severe disease,” Dr. Garjani said.

“We found similar trends of rates of infection in MS patients and the general population, and no signal of increased risks in those with higher EDSS or progressive MS. The caveat is that this study was conducted in a period of lockdown, but we adjusted for self-isolating behavior in the multivariable regression analysis,” she noted.

Dr. Salter is a statistical editor for the American Heart Association journal Circulation: Cardiovascular Imaging. Dr. Garjani has disclosed no relevant financial relationships.

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

The risk of severe outcomes from COVID-19 infection in patients with multiple sclerosis (MS) seems to align with that seen in the general population, new U.S. data suggest. A separate study from the United Kingdom also found similar trends of rates of COVID-19 infection in patients with MS and the general population.

Both studies were presented Sept. 26 at a special session on multiple sclerosis and COVID-19 at a final “Encore” event as part of the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The U.S. data appear consistent with studies from several other countries, in that worse COVID-19 outcomes increase with age and higher disability levels, both of which would be expected from findings in the general population.

The U.S. data also show a clear effect of race in MS, with higher rates of adverse COVID-19 outcomes in Black patients, again in line with what is seen in the general population.

“I would say the results from our study and in general do not suggest that MS itself is associated with higher risks of severe COVID-19 outcomes, compared with the general population,” said Amber Salter, PhD.

Dr. Salter, who is assistant professor of biostatistics at Washington University, St. Louis, presented data from the COViMS North American registry, set up for health care providers to report persons with MS who are infected with COVID-19.

The COViMS registry so far has information on 858 patients with MS who have COVID-19 (80% verified by a positive test), as reported from 150 different health care providers in the United States and Canada. The average age was 48 years, with average disease duration of 13.6 years. MS clinical course was reported as relapsing remitting in 78%, secondary progressive in 15%, and primary progressive in 5%. Most patients (72%) were fully ambulatory, 16% could walk with assistance, and 12% were nonambulatory.

Severe COVID-19 outcomes were classified as mortality (which occurred in 5.7% of the cohort), mortality/ICU admission (13.6%) and mortality/ICU admission/hospitalization (30.2%).

Results were adjusted for many different covariates, including sex, age, smoking, MS clinical course (relapsing, progressive), disease duration, ambulation, individual comorbidities (cardiovascular disease, cerebrovascular disease, chronic kidney disease, chronic lung disease, diabetes, hypertension, morbid obesity), and disease-modifying therapy use.

In multivariable logistic regression analyses, older age, having chronic renal disease, and being nonambulatory were consistently associated with increased odds of poorer outcomes. Chronic kidney disease had the strongest association with mortality (odds ratio, 28.6; P < .001). Other factors associated with mortality included cardiovascular disease (OR, 4.35; P = .009); age (OR per 10 years, 1.91; P = .012), and male sex (OR, 2.60; P = .041).

Patients who were nonambulatory had a higher risk of mortality/ICU admission/hospitalization (OR, 3.32; P = .003). This endpoint was also increased in patients on anti-CD20 drugs, compared with other disease-modifying treatment (OR, 2.31; P = .002), consistent with results from at least two other studies.

Disease-modifying therapy in general was not associated with an increased risk of worse outcomes. “There was some concern at the outset about the effect of disease-modifying therapies on COVID-19 outcomes, but most studies have not found an increased risk of worse outcomes in patients on such drug treatments, with the possible exception of anti-CD20 drugs,” Dr. Salter said.

“Some disease-modifying therapies may actually be protective (particularly interferon) and studies are investigating whether they may have a role in the treatment of COVID-19,” she added.

“The factors in MS patients that we and others have found to be associated with worse COVID-19 outcomes may not be specific to MS. Older age is known to be a primary risk factor for worse COVID-19 outcomes in the general population, and increasing disability presumably tracks with worse general heath,” Dr. Salter commented.

“I would say the overall data are fairly reassuring for MS patents,” she concluded.
 

Black patients have higher risk

One worrying finding in the North American data, however, was the effect of race. “We found an independent effect of race for worse COVID-19 outcomes in MS patients,” Dr. Slater said.

Of the 858 patients in the COViMS registry, 65.7% were White and 26.1% were Black. Black individuals were more likely to be younger, never smokers, have shorter MS duration, a relapsing MS course, and have comorbidities, compared with White patients. A higher proportion of Black patients had hypertension (40.2% vs 19.5%) and morbid obesity (17% vs. 9.5%).

Results showed that mortality rates were not statistically different between White and Black patients, but Black race was associated with increased risk of mortality and/or ICU admission, compared with White patients (16.9% vs. 12.8%), and multivariate logistic regression analysis showed Black race was independently associated with mortality/ICU admission after adjustments for covariates (OR, 3.7; P = .002).

Black race was also associated with increased risk of mortality/ICU admission/hospital admission (35.8% vs. 30.2%), and after adjustment for covariates this was found to be an independent predictor (OR, 1.7; P = .04).

“This higher COVID-19 risk in Black individuals is also seen in the general population, so these results are not that surprising and it doesn’t appear to be an effect specific to MS patients,” Dr. Salter commented.
 

U.K. data on risk of contracting COVID-19 

A U.K. study also suggested race to be an independent predictor in the risk of contracting COVID-19 in patients with MS.

The study of more than 5,000 patients with MS showed that those from a Black, Asian, and Minority Ethnic group were twice as likely to report having COVID-19 than those who were White.

The study, which was conducted during the U.K. lockdown, also found that the trend of COVID-19 infection in patients with MS is comparable with that of the U.K. general population.

Presenting the data, Afagh Garjani, MD, concluded: “During a period with strict physical distancing measures, patients with MS are not at an increased risk of contracting COVID-19.”

Dr. Garjani, a neurology clinical research fellow at the University of Nottingham, (England), explained that the COVID-19 pandemic has introduced uncertainties into the MS community, and the focus so far has been the severity of infection among people with MS who have COVID-19.

“This approach has left questions about the risk of contracting disease in people with MS unanswered, which has implications as society gradually returns to normal,” she said.

Dr. Garjani presented data from the United Kingdom MS Register (UKMSR), which has been collecting demographic and MS-related data since 2011 from patients with MS throughout the United Kingdom.

On March 17 – just before the lockdown in United Kingdom – existing participants of the UKMSR were asked to join the COVID-19 study. The study was also advertised through social media. In this ongoing study, people with MS answered a COVID-19–related survey at participation and a different follow-up survey every 2 weeks depending on whether they contracted COVID-19.

The COVID-19 study included 5,309 patients with MS. The mean age of the study population was 52.4 years, 76.1% were female, and 95.7% were White. Of the 5,309 patients, 535 (10%) reported a self-diagnosis of COVID-19. Because of limited availability of tests in the United Kingdom at the time, only 75 patents had a positive polymerase chain reaction result.

“To our knowledge, this is the largest community-based study of COVID-19 in patients with MS worldwide,” Dr. Garjani said. She presented results from the period March 23 to June 24, when the United Kingdom was in a period of lockdown with vulnerable groups encouraged to self-isolate completely.

In this MS cohort, 47% reported self-isolating at some point. Those at older age and higher Expanded Disability Status Scale (EDSS) score were more likely to have self-isolated.

The researchers did not find that patients with progressive MS or those on disease-modifying therapies in general isolated more, but patients on monoclonal antibody drugs and fingolimod were more likely to self-isolate versus those on other therapies. “This may be because there are concerns about infection with these drugs and patients on these therapies may be more concerned about contracting COVID-19,” Dr. Garjani suggested.

In terms of contracting COVID, the researchers found a reduced risk of COVID-19 (self-diagnosed) in patients with older age and higher EDSS. “This is not really surprising that these patients were more likely to self-isolate,” Dr. Garjani commented.

No association was seen between type of MS, disease duration, disease-modifying therapy in general, and risk of COVID-19. No individual drug treatment increased risk versus no therapy or versus self-injectables. But there was an increased risk of contracting the virus in patients whose race was Black, Asian, or Minority Ethnic (OR, 2.2), which is in line with findings from the general population.

“This study is unique – the denominator is all people with MS. We are looking primarily at the risk of contracting COVID-19. Other studies are focusing more on people with MS who have COVID and assessing risk of a severe COVID outcome. Our results are not contradicting the findings from those studies,” Dr. Garjani said.

The results were similar only when patients with a confirmed COVID-19 test were considered.

In terms of outcomes in those who reported COVID-19 infection, preliminary results have not shown any MS factors – such as EDSS, age, type of MS, drug therapy in general – to be associated with outcome.

“Since the COVID-19 outbreak started there has been concern among MS patients, especially among those on disease-modifying therapies, about whether they are at increased risk of infection and severe disease,” Dr. Garjani said.

“We found similar trends of rates of infection in MS patients and the general population, and no signal of increased risks in those with higher EDSS or progressive MS. The caveat is that this study was conducted in a period of lockdown, but we adjusted for self-isolating behavior in the multivariable regression analysis,” she noted.

Dr. Salter is a statistical editor for the American Heart Association journal Circulation: Cardiovascular Imaging. Dr. Garjani has disclosed no relevant financial relationships.

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

The risk of severe outcomes from COVID-19 infection in patients with multiple sclerosis (MS) seems to align with that seen in the general population, new U.S. data suggest. A separate study from the United Kingdom also found similar trends of rates of COVID-19 infection in patients with MS and the general population.

Both studies were presented Sept. 26 at a special session on multiple sclerosis and COVID-19 at a final “Encore” event as part of the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The U.S. data appear consistent with studies from several other countries, in that worse COVID-19 outcomes increase with age and higher disability levels, both of which would be expected from findings in the general population.

The U.S. data also show a clear effect of race in MS, with higher rates of adverse COVID-19 outcomes in Black patients, again in line with what is seen in the general population.

“I would say the results from our study and in general do not suggest that MS itself is associated with higher risks of severe COVID-19 outcomes, compared with the general population,” said Amber Salter, PhD.

Dr. Salter, who is assistant professor of biostatistics at Washington University, St. Louis, presented data from the COViMS North American registry, set up for health care providers to report persons with MS who are infected with COVID-19.

The COViMS registry so far has information on 858 patients with MS who have COVID-19 (80% verified by a positive test), as reported from 150 different health care providers in the United States and Canada. The average age was 48 years, with average disease duration of 13.6 years. MS clinical course was reported as relapsing remitting in 78%, secondary progressive in 15%, and primary progressive in 5%. Most patients (72%) were fully ambulatory, 16% could walk with assistance, and 12% were nonambulatory.

Severe COVID-19 outcomes were classified as mortality (which occurred in 5.7% of the cohort), mortality/ICU admission (13.6%) and mortality/ICU admission/hospitalization (30.2%).

Results were adjusted for many different covariates, including sex, age, smoking, MS clinical course (relapsing, progressive), disease duration, ambulation, individual comorbidities (cardiovascular disease, cerebrovascular disease, chronic kidney disease, chronic lung disease, diabetes, hypertension, morbid obesity), and disease-modifying therapy use.

In multivariable logistic regression analyses, older age, having chronic renal disease, and being nonambulatory were consistently associated with increased odds of poorer outcomes. Chronic kidney disease had the strongest association with mortality (odds ratio, 28.6; P < .001). Other factors associated with mortality included cardiovascular disease (OR, 4.35; P = .009); age (OR per 10 years, 1.91; P = .012), and male sex (OR, 2.60; P = .041).

Patients who were nonambulatory had a higher risk of mortality/ICU admission/hospitalization (OR, 3.32; P = .003). This endpoint was also increased in patients on anti-CD20 drugs, compared with other disease-modifying treatment (OR, 2.31; P = .002), consistent with results from at least two other studies.

Disease-modifying therapy in general was not associated with an increased risk of worse outcomes. “There was some concern at the outset about the effect of disease-modifying therapies on COVID-19 outcomes, but most studies have not found an increased risk of worse outcomes in patients on such drug treatments, with the possible exception of anti-CD20 drugs,” Dr. Salter said.

“Some disease-modifying therapies may actually be protective (particularly interferon) and studies are investigating whether they may have a role in the treatment of COVID-19,” she added.

“The factors in MS patients that we and others have found to be associated with worse COVID-19 outcomes may not be specific to MS. Older age is known to be a primary risk factor for worse COVID-19 outcomes in the general population, and increasing disability presumably tracks with worse general heath,” Dr. Salter commented.

“I would say the overall data are fairly reassuring for MS patents,” she concluded.
 

Black patients have higher risk

One worrying finding in the North American data, however, was the effect of race. “We found an independent effect of race for worse COVID-19 outcomes in MS patients,” Dr. Slater said.

Of the 858 patients in the COViMS registry, 65.7% were White and 26.1% were Black. Black individuals were more likely to be younger, never smokers, have shorter MS duration, a relapsing MS course, and have comorbidities, compared with White patients. A higher proportion of Black patients had hypertension (40.2% vs 19.5%) and morbid obesity (17% vs. 9.5%).

Results showed that mortality rates were not statistically different between White and Black patients, but Black race was associated with increased risk of mortality and/or ICU admission, compared with White patients (16.9% vs. 12.8%), and multivariate logistic regression analysis showed Black race was independently associated with mortality/ICU admission after adjustments for covariates (OR, 3.7; P = .002).

Black race was also associated with increased risk of mortality/ICU admission/hospital admission (35.8% vs. 30.2%), and after adjustment for covariates this was found to be an independent predictor (OR, 1.7; P = .04).

“This higher COVID-19 risk in Black individuals is also seen in the general population, so these results are not that surprising and it doesn’t appear to be an effect specific to MS patients,” Dr. Salter commented.
 

U.K. data on risk of contracting COVID-19 

A U.K. study also suggested race to be an independent predictor in the risk of contracting COVID-19 in patients with MS.

The study of more than 5,000 patients with MS showed that those from a Black, Asian, and Minority Ethnic group were twice as likely to report having COVID-19 than those who were White.

The study, which was conducted during the U.K. lockdown, also found that the trend of COVID-19 infection in patients with MS is comparable with that of the U.K. general population.

Presenting the data, Afagh Garjani, MD, concluded: “During a period with strict physical distancing measures, patients with MS are not at an increased risk of contracting COVID-19.”

Dr. Garjani, a neurology clinical research fellow at the University of Nottingham, (England), explained that the COVID-19 pandemic has introduced uncertainties into the MS community, and the focus so far has been the severity of infection among people with MS who have COVID-19.

“This approach has left questions about the risk of contracting disease in people with MS unanswered, which has implications as society gradually returns to normal,” she said.

Dr. Garjani presented data from the United Kingdom MS Register (UKMSR), which has been collecting demographic and MS-related data since 2011 from patients with MS throughout the United Kingdom.

On March 17 – just before the lockdown in United Kingdom – existing participants of the UKMSR were asked to join the COVID-19 study. The study was also advertised through social media. In this ongoing study, people with MS answered a COVID-19–related survey at participation and a different follow-up survey every 2 weeks depending on whether they contracted COVID-19.

The COVID-19 study included 5,309 patients with MS. The mean age of the study population was 52.4 years, 76.1% were female, and 95.7% were White. Of the 5,309 patients, 535 (10%) reported a self-diagnosis of COVID-19. Because of limited availability of tests in the United Kingdom at the time, only 75 patents had a positive polymerase chain reaction result.

“To our knowledge, this is the largest community-based study of COVID-19 in patients with MS worldwide,” Dr. Garjani said. She presented results from the period March 23 to June 24, when the United Kingdom was in a period of lockdown with vulnerable groups encouraged to self-isolate completely.

In this MS cohort, 47% reported self-isolating at some point. Those at older age and higher Expanded Disability Status Scale (EDSS) score were more likely to have self-isolated.

The researchers did not find that patients with progressive MS or those on disease-modifying therapies in general isolated more, but patients on monoclonal antibody drugs and fingolimod were more likely to self-isolate versus those on other therapies. “This may be because there are concerns about infection with these drugs and patients on these therapies may be more concerned about contracting COVID-19,” Dr. Garjani suggested.

In terms of contracting COVID, the researchers found a reduced risk of COVID-19 (self-diagnosed) in patients with older age and higher EDSS. “This is not really surprising that these patients were more likely to self-isolate,” Dr. Garjani commented.

No association was seen between type of MS, disease duration, disease-modifying therapy in general, and risk of COVID-19. No individual drug treatment increased risk versus no therapy or versus self-injectables. But there was an increased risk of contracting the virus in patients whose race was Black, Asian, or Minority Ethnic (OR, 2.2), which is in line with findings from the general population.

“This study is unique – the denominator is all people with MS. We are looking primarily at the risk of contracting COVID-19. Other studies are focusing more on people with MS who have COVID and assessing risk of a severe COVID outcome. Our results are not contradicting the findings from those studies,” Dr. Garjani said.

The results were similar only when patients with a confirmed COVID-19 test were considered.

In terms of outcomes in those who reported COVID-19 infection, preliminary results have not shown any MS factors – such as EDSS, age, type of MS, drug therapy in general – to be associated with outcome.

“Since the COVID-19 outbreak started there has been concern among MS patients, especially among those on disease-modifying therapies, about whether they are at increased risk of infection and severe disease,” Dr. Garjani said.

“We found similar trends of rates of infection in MS patients and the general population, and no signal of increased risks in those with higher EDSS or progressive MS. The caveat is that this study was conducted in a period of lockdown, but we adjusted for self-isolating behavior in the multivariable regression analysis,” she noted.

Dr. Salter is a statistical editor for the American Heart Association journal Circulation: Cardiovascular Imaging. Dr. Garjani has disclosed no relevant financial relationships.

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

Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.

Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.

She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.

Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York

Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.

Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.

She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.

Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York

Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.

Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.

She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.

Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York

Promising imaging developments may soon improve clinicians' ability to diagnose and monitor the progression of multiple sclerosis (MS). Dr Patricia Coyle, director of the Multiple Sclerosis Comprehensive Care Center at Stony Brook University Medical Center, reports on findings presented at the 8th Joint ACTRIMS-ECTRIMS Conference, this year known as MSVirtual 2020.

Dr Coyle emphasizes the importance of appropriate diagnosis as well as the need to improve the misdiagnosis rate. Advanced monitoring techniques that can detect MS with more accuracy are key. 

She highlights exciting research in novel MRI markers, including central vein sign and paramagnetic rim sign (PRS). One study shows reliable methods for quantification of PRS, which is especially critical if this prognostic marker is to be adopted for clinical practice. 

Dr Coyle highlights other studies focused on techniques that help monitor the damage from progressing MS, including further analysis of optical coherence tomography. 
 

Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York

Promising imaging developments may soon improve clinicians' ability to diagnose and monitor the progression of multiple sclerosis (MS). Dr Patricia Coyle, director of the Multiple Sclerosis Comprehensive Care Center at Stony Brook University Medical Center, reports on findings presented at the 8th Joint ACTRIMS-ECTRIMS Conference, this year known as MSVirtual 2020.

Dr Coyle emphasizes the importance of appropriate diagnosis as well as the need to improve the misdiagnosis rate. Advanced monitoring techniques that can detect MS with more accuracy are key. 

She highlights exciting research in novel MRI markers, including central vein sign and paramagnetic rim sign (PRS). One study shows reliable methods for quantification of PRS, which is especially critical if this prognostic marker is to be adopted for clinical practice. 

Dr Coyle highlights other studies focused on techniques that help monitor the damage from progressing MS, including further analysis of optical coherence tomography. 
 

Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York

Promising imaging developments may soon improve clinicians' ability to diagnose and monitor the progression of multiple sclerosis (MS). Dr Patricia Coyle, director of the Multiple Sclerosis Comprehensive Care Center at Stony Brook University Medical Center, reports on findings presented at the 8th Joint ACTRIMS-ECTRIMS Conference, this year known as MSVirtual 2020.

Dr Coyle emphasizes the importance of appropriate diagnosis as well as the need to improve the misdiagnosis rate. Advanced monitoring techniques that can detect MS with more accuracy are key. 

She highlights exciting research in novel MRI markers, including central vein sign and paramagnetic rim sign (PRS). One study shows reliable methods for quantification of PRS, which is especially critical if this prognostic marker is to be adopted for clinical practice. 

Dr Coyle highlights other studies focused on techniques that help monitor the damage from progressing MS, including further analysis of optical coherence tomography. 
 

Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York