What’s New in MS Research – November 2020

Latest News, What's New in MS Research November 23, 2020

Reviewed by MSAA Chief Medical Officer Barry A. Hendin, MD

Introduction

While we all know “MS” stands for “multiple sclerosis,” with so much exciting research reported in this edition of “What’s New in MS Research,” we can almost imagine that “MS” could also refer to the quest for “multiple solutions” in MS. Although a great deal of the research looks to further understand the biology, easing the symptoms, and slowing or stopping the physical damage of MS, the studies and other information presented here are very encouraging – and they are only a small sample of the vast array of research under way around the world.

Most of the clinical trials and other studies featured in this issue of “What’s New in MS Research” are drawn from virtual presentations given at the September 2020 joint meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

That meeting, held virtually this year due to the COVID-19 pandemic, was a forum for laboratory scientists and clinical investigators to share their findings from literally thousands of research efforts. As reflected in the reports that follow, those inquiries touch upon everything from enhancing the diagnosis of MS and better understanding its course, to evaluating the effectiveness and safety of approved disease-modifying therapies, investigational agents, and other types of interventions.

Studies with Approved Disease-Modifying Therapies

Impact of Vumerity on brain-volume change: Encouraging interim findings

People with relapsing MS who took the oral disease-modifying therapy Vumerity^® (diroximel fumarate) for up to two years had changes (reductions) in brain volume that approach those seen in people who do not have MS.

That’s the encouraging finding from interim results of a study examining the long-term impact of the medication, which the FDA approved in October 2019.¹ The study, EVOLVE-MS-1, is an ongoing, open-label Phase 3 investigation. Analysis of data on 365 patients who had taken Vumerity for a median of 96 weeks showed that their average percent of brain volume change (PBVC) was -0.36 from baseline to Week 48 and -0.35 from Week 48 to Week 96. Meanwhile, the estimated proportion of patients who were free of confirmed disability progression was 94.3% at Week 48 and 90.7% at Week 96. The proportions of patients with no evidence of disease activity at Week 48 and Week 96 were 44.7% and 25.2%, respectively.

The study’s authors noted, “Interim findings from the ongoing EVOLVE-MS-1 study demonstrate that yearly PBVC in [Vumerity]-treated patients approached the rate observed in healthy adults.”

Newly approved DMT shows efficacy in newly diagnosed, treatment-naïve patients

In August, Kesimpta^® (ofatumumab) became the first self-administered targeted B-cell therapy approved by the FDA to treat relapsing forms of MS. A recent analysis of data from the Phase III ASCLEPIOS I/II trials that led to that approval provide insights into the efficacy and risk profile of the anti-CD20 monoclonal antibody in newly diagnosed patients who had not received any prior disease-modifying therapy (DMT) for their MS.² The analysis involved 615 patients with a median age of 36 years who typically had been diagnosed within a year of starting either Kesimpta, or the comparison agent Aubagio^® (teriflunomide), in the Phase III trials.

Compared to Aubagio, the study found that Kesimpta reduced the annual relapse rate (ARR) by 50.3%. It also reduced six-month confirmed disability worsening by 46%, and the number of new or enlarging T2 lesions seen on magnetic resonance imaging (MRI) in a year by 82.0%.

The study’s authors noted that these findings in newly diagnosed patients who had not received prior DMTs were consistent with results for the overall study population.

Assessing the long-term impact of Mayzent in secondary-progressive MS

Mayzent ^® (siponimod) is an oral DMT approved by the FDA in March 2019 as a treatment for both relapsing and active secondary-progressive MS (aSPMS). In the EXPAND trial that led to its approval, the medication reduced worsening of both clinical disability and cognition at the six-month mark in people with aSPMS. New data show that those benefits may continue for up to five years.³

An analysis assessed long-term outcomes in 582 people with aSPMS, comparing those who had received Mayzent throughout the EXPAND trial and its open-label extension (Continuous Group), with those who had been on placebo during the main trial and then switched to Mayzent during the extension (Switch Group).

Median time to confirmed disability progression over any six-month period was 48 months for the Switch Group, but was not reached for the Continuous Group. Similarly, the risk of confirmed cognitive worsening over any six-month period was reduced by 33% in the Continuous Group vs. the Switch Group, a statistically significant difference. The annual relapse rate (ARR) was also significantly reduced in the Continuous Group relative to the Switch Group.

The study’s authors concluded, “Long-term data analyses in the Continuous versus Switch groups showed that siponimod treatment effects on disability, cognitive processing speed, and relapse outcomes in patients with active SPMS are sustained for up to 5 years, and highlight the value of early treatment initiation.”

References
¹ Arnold D, et al. Effects of diroximel fumarate on brain volume change and disability progression in adults with relapsing-remitting multiple sclerosis from EVOLVE-MS-1. ECTRIMS 2020 [P0205].

² Gartner J, et al. Benefit-risk of ofatumumab in treatment-naïve early relapsing multiple sclerosis patients. ECTRIMS 2020 [P0192].

³ Giovannoni G, et al. Sustained reduction of disability and cognitive decline with long-term siponimod treatment in patients with active SPMS: EXPAND data up to 5 years. ECTRIMS 2020 [P0238].

Experimental Disease-Modifying Therapies

Evaluating the impact of ponesimod on brain volume and other measures

Ponesimod is an oral medication in late stages of investigation for treatment of relapsing forms of MS. It belongs to a class of medications called sphingosine-1-phosphate receptor 1 modulators. The class also includes FDA-approved disease-modifying therapies (DMTs) such as Gilenya^® (fingolimod) and Mayzent^® (siponimod). The Phase III OPTIMUM study evaluated the efficacy and safety of ponesimod relative to the approved DMT Aubagio^® (teriflunomide) over two years of treatment. The study included 985 patients. ⁴

Analysis of magnetic resonance imaging (MRI) findings and other data from the trial showed that patients in the ponesimod group had less change in brain volume than those taking Aubagio and fewer new or enlarging T2 lesions seen on MRI per year. Further, at week 108 of treatment, 28.2% of patients receiving ponesimod had no evidence of disease activity as assessed by three measures (NEDA-3), compared to 18.3% of people taking Aubagio.

Evobrutinib shows two-year reduction in relapse rate

Evobrutinib is an investigational medication that belongs to a class of medications known as Bruton’s tyrosine kinase inhibitors, or BTKIs. Its developers note that it has a dual mode of action, targeting B cells and myeloid cells, both of which play a role in autoimmune diseases such as multiple sclerosis (MS). In a recent Phase II trial involving people with relapsing MS, evobrutinib significantly reduced T1 gadolinium-enhancing lesions on MRI compared to placebo at Week 24, and showed continued efficacy through Week 48.⁵

Patients who participated in that trial were eligible to join an open-label extension study that tracked clinical relapse rates and other measures. The extension included both people who had received various doses of evobrutinib in the Phase II trial and those who had received placebo. All participants in the extension study received evobrutinib.

Among 148 patients who completed 108 weeks of treatment, those who had been on the highest dose of evobrutinib in the main trial had an annualized relapse rate of 0.12, which was roughly one-third that of the 0.31 rate for patients who received placebo in the main trial before switching to evobrutinib in the open-label period. Similarly, the estimated time to relapse in the higher-dose evobrutinib patients was almost three times longer than that of patients who started on placebo.

Development of opicinumab discontinued

For all of the remarkable progress that has been made in expanding treatment options for MS, there also are periodic reminders that drug development is a difficult and complex process that offers no guarantees of success.

One such reminder came a few weeks ago, when Biogen noted in its third-quarter report that it will discontinue development of its investigational agent opicinumab.⁶ The medication, which is also known as anti-LINGO-1 and BIIB033, is an antibody that was thought to promote repair of the myelin sheath that protects nerves. Damage to that sheath is the hallmark of MS.

The agent has been studied in a number of Phase II studies, including RENEW, SYNERGY, and the AFFINITY trial, which was scheduled to run until 2022. Unfortunately, the latter trial did not meet primary or secondary endpoints, so development of opicinumab was discontinued.

References

⁴ Kappos L, et al. Effect of oral ponesimod on clinical disease activity and MRI-based outcomes in patients with relapsing multiple sclerosis: Phase 3 OPTIMUM study. ECTRIMS 2020 [P0071].

⁵ Montalban X, et al. Clinical relapse rates in relapsing MS patients treated with the BTK inhibitor evobrutinib: results of an open-label extension to a Phase II study. ECTRIMS 2020 [P0197].

⁶ Biogen. Third Quarter 2020: Financial Results and Business Update. October 21, 2020. Available at https://investors.biogen.com/static-files/7d40149f-af6a-4bcb-8bd0-97b18ff2d9fd.

MS Diagnosis, Course, and Impact

sNfL: An emerging biomarker continues to make its mark on MS diagnosis and prognosis

Further support for the role of serum neurofilament light chain (sNfL) in diagnosing MS and predicting its course emerged from several studies presented at the September 2020 joint virtual meeting of ACTRIMS and ECTRIMS. Two of those studies are summarized below.

Neurofilament light, or NfL, is a protein found in axons, the component of neurons that facilitates transmission of electrical impulses. When neurons are damaged, as occurs in MS and other diseases, the protein is released, eventually reaching the blood, or serum. Researchers seeking biomarkers that can help correctly identify MS and provide clues to its future course have focused in recent years on the sNfL chain, with generally encouraging results.

In a multi-center, prospective study, investigators looked for an association between sNfL levels and the diagnosis of MS, MRI parameters, and treatment decisions.⁷ The study, which involved 814 patients, found that:

Patients with clinically isolated syndrome (CIS) had lower sNfL levels than those with MS, a finding that may help clinicians distinguish between the two conditions.
sNfL levels correlated with the number of clinical relapses a person experienced and the number of gadolinium-enhancing lesions seen on MRI.
Patients who received disease-modifying therapies (DMTs) in the first two years after diagnosis had higher baseline sNfL levels than patients who did not receive a DMT, suggesting that they may have presented with more pronounced symptoms. Further, sNfL levels measured over four years reflected treatment decisions, supporting the idea that those levels are a marker of disease status.
The study’s authors concluded that evaluating sNfL levels may both enhance diagnosis and help guide decisions about initial treatment.

A second study found that sNfL levels obtained in the early stages of MS can predict how patients are likely to fare as much as 15 years later.⁸ Drawing on long-term data from the BENEFIT study examining use of interferon beta-1b in people with MS, researchers found that patients with baseline sNfL values above the 90th percentile were almost 2.5 times more likely than people with lower sNfL concentrations to have an Expanded Disability Status Scale (EDSS) score of 4 or greater 15 years later. An EDSS score of 4 indicates that although fully ambulatory and self-sufficient, an individual is experiencing significant disability.

One less headache for people with MS who also suffer from migraines

It could be intuitive to think – or at least to worry – that a history of migraines would not bode well for the course of MS, but researchers have found that this isn’t necessarily the case.⁹

Those investigators analyzed data on 2,017 people with MS, including 336 people who had reported experiencing migraines. The people who reported migraines tended to be younger than the other patients, and were more likely to also have a history of anxiety, depression, and obstructive sleep apnea. However, they were less likely than the other study subjects to have severe disability (5.4% of those with migraine vs. 12.0% of those without, a statistically significant difference), and did not show differences in walking speed, manual dexterity, cognitive processing speed, relapse rates, or rate of new brain-lesion development.

While the investigators cautioned that the evidence gathered to date on migraine and MS is conflicting, and that further studies are needed, their findings nonetheless offer reassurance to people who may have feared that migraine headaches would somehow contribute to or be associated with a more-difficult MS course.

Different types of MS impact quality of life similarly

Depression, pain, and walking difficulty are the symptoms that have the greatest impact on quality of life for people with MS, regardless of which form of the condition they have. This is the main finding to emerge from a study examining how 13 different MS symptoms affected health-related quality of life (HRQoL) in 1,985 people with MS.¹⁰

Although the study subjects were stratified by MS phenotype, such as relapsing-remitting MS, secondary-progressive MS, and primary-progressive MS, the investigators found that depression, pain, and problems with walking were the main contributors to a reduced quality of life across and among the different subgroups. “Reducing these symptoms may have the largest impact on improving HRQoL in all MS phenotypes of people with MS,” they said.

References
⁷ Bittner S, et al. Serum neurofilament predicts clinical progression and increases diagnostic accuracy in patients with early multiple sclerosis. ECTRIMS 2020 [P0263].

⁸ Kuhle J, et al. Prediction of 15-year MS outcomes in BENEFIT trial patients using serum neurofilament light chain concentrations. ECTRIMS 2020 [P0132].

⁹ Damian A, et al. A history of migraine headache may not be associated with worse disability or worse neurologic function. ECTRIMS 2020 [P0423].

¹⁰ Zhang Y, et al. Feelings of depression, pain and walking difficulties have the largest impact on the quality of life of people with MS, irrespective of MS phenotype. ECTRIMS 2020 [P1032].

Specific Patient Populations

An MS trial focused exclusively on minority patients

In keeping with efforts to address long-standing inequities in society as a whole and within the healthcare system, a new trial will evaluate the efficacy and safety of the disease-modifying therapy Ocrevus^® (ocrelizumab) in people with relapsing forms of MS who are of African ancestry or Hispanic and Latino ethnicity.

In previewing the trial, researchers noted that minority patients with MS tend to have greater disease severity and faster progression than Caucasians, but are significantly under-represented in clinical trials, “owing to poor access and cultural, economic and other participation barriers.” They added that while large-scale clinical trials of Ocrevus showed that the B cell-targeting anti-CD20 therapy reduced rates of disease activity and progression in both relapsing MS and primary-progressive MS, minority participation in those studies was less than 10%.¹¹

By contrast, the researchers said, the single-arm Phase IV study, called CHIMES, is an industry-sponsored collaborative approach designed to meet the needs of patients of African or Hispanic ancestry.

The study’s primary endpoint will be disease activity, defined by the proportion of patients free of protocol-defined events such as relapses, at one year. Study subjects will be eligible to participate in a second-year extension that will assess disease progression and biomarker endpoints. One-third of the patients will take part in a sub-study evaluating cerebrospinal fluid biomarkers.

The researchers noted, “Findings from CHIMES are expected to improve current understanding of MS disease biology, treatment response and clinical trial participation among [African ancestry and Hispanic ancestry] patients with MS, with the ultimate goals of increasing high-quality standard of care to traditionally underserved populations and enhancing equality through clinical research.”

Examining MS relapse rates during – and after – pregnancy

A new study has bolstered prior findings that MS relapses tend to decrease during pregnancy and then increase again in the early postpartum period.¹²

The analysis assessed information on 119 women who became pregnant while they were patients at the University of California San Francisco Multiple Sclerosis Center during the period 2005 to 2018. For the 146 live-birth pregnancies that the study subjects had, the pre-pregnancy annual relapse rate (ARR) was 0.33. That rate decreased during pregnancy to 0.10 but then increased to 0.61 by three months after delivery. (Both changes were statistically significant.)

Another key finding: Women who exclusively breastfed their babies for at least three months after delivery had a significantly reduced likelihood of having a relapse.

Identifying indicators of long-term disability in children with MS

Children and adolescents who have optic nerve, brainstem, or spinal cord lesions when they are diagnosed with MS are at greater risk for long-term disability than other pediatric MS patients. That was one of the major findings to emerge from a study of 123 young people followed for an average of nine years after diagnosis.¹³

Researchers found that optic nerve involvement at baseline predicted a shorter time to first relapse and 10-year disability worsening. Brainstem lesions at baseline also were predictive of 10-year disability worsening, as well as of a higher 10-year Expanded Disability Status Scale (EDSS) score. The number of cervical spinal cord lesions at diagnosis also helped identify patients likely to have higher EDSS scores 10 years after diagnosis. Several other clinical and imaging features seen in the first three years after diagnosis, including number of relapses in the first year and detection of at least two lesions seen on MRI within two years, also provided reliable information on long-term disease course.

The study’s investigators noted, “Accurate clinical and MRI monitoring during the first two years of disease has proven to represent a powerful tool for counseling [pediatric] patients about long-term prognosis and personalizing treatment strategies.”

References
¹¹ Williams M, et al. Treating minority patients with multiple sclerosis: development of the CHIMES trial. ECTRIMS 2020 [P0242].

¹² Anderson A, et al. Clinical and radiologic disease activity in pregnancy and postpartum in multiple sclerosis. ECTRIMS 2020 [P1117].

¹³ De Meo E, et al. Early clinical and MRI predictors of long-term disability in pediatric multiple sclerosis patients. ECTRIMS 2020 [P1075].

Other Interventions

Comparing stem cell transplantation with disease-modifying therapies

Encouraging results from small- and medium-sized studies have generated considerable interest in treating multiple sclerosis with stem cell therapy, but important questions remain about the long-term outcomes of the treatment strategy, as well as about how it compares with current disease-modifying therapies (DMTs).

The StarMS study will examine that last issue: the safety and efficacy of stem cell transplantation relative to DMTs.¹⁴ Funded by the British government, the study will involve 198 people with relapsing-remitting MS. One half of the study participants will receive stem cells that have been taken from their body, treated, and then re-infused after the patient undergoes immunosuppression. This approach is designed to “reboot” the immune system. The other half of the participants will receive one of two DMTs, Ocrevus^® (ocrelizumab) or Lemtrada^® (alemtuzumab).

The primary endpoint of the study will be the rate of patients achieving no evidence of disease activity (NEDA), based on clinical and imaging assessments, over a two-year follow-up period. Allowing time for full patient enrollment, results are expected in about four years.

Study investigators note, “The StarMS trial has the potential to provide definitive data on the comparative efficacy of aHSCT [autologous hematopoietic stem cell transplantation] versus highly efficacious DMTs, help improve patient outcomes, and impact national and international guidelines.”

Targeting brain metabolism with gold nanocrystals

Might administering microscopic crystals to people with MS prove to be the gold standard – literally – for repairing the nerve-sheath damage that drives MS?

Clene Nanomedicine, a biopharmaceutical company based in Salt Lake City, Utah, is pursuing the answer to that question as it develops CNM-Au8, a concentrated, aqueous suspension of clean-surfaced faceted gold nanocrystals that act catalytically to support intracellular biological reactions. The agent is being investigated as a potential treatment not only for MS, but also for Parkinson’s disease (PD) and potentially other neurological conditions.

Studies in animals indicate that CNM-Au8 has both remyelination and neuroprotective effects, the Company notes. Clene Nanotechnologies adds that Phase I studies in healthy human volunteers have demonstrated the safety of CNM-Au8.¹⁵

As a next step in the research process, the Company organized the REPAIR-MS and REPAIR-PD studies. The Phase II, single-center, open-label, imaging studies are examining the brain metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who have been diagnosed with MS in the past 15 years (REPAIR-MS) or who have been diagnosed with PD in the past three years (REPAIR-PD). Study participants take either a 15 or 30 mg orally delivered dose of the nanocrystal suspension each morning.

Study participants undergo sophisticated brain imaging scanning to assess key bioenergetic brain metabolites at baseline, prior to administration of CNM-Au8, and at the end of the study. The objective is to show that CNM-Au8 engages with targeted central nervous system biomarkers related to bioenergetics and neuronal metabolism in people with MS and PD. The study is taking place at University of Texas Southwestern Medical Center.

Survey finds that one in five people with MS are using cannabis for symptom relief

Roughly one-third of people with MS have looked to cannabis at least once for relief of spasticity or pain, or to help with sleep, and 20% currently are taking cannabis to ease MS symptoms.¹⁶ Those were the main findings of a recent online survey conducted by the North American Research Committee on Multiple Sclerosis, or NARCOMS, a voluntary self-report registry for people with MS.

NARCOMS researchers invited 6,934 registry participants to complete the survey. Forty-seven percent – or 3,249 people – responded. The participants had an average age of 61.2 years and a mean age at MS symptom onset of 31.2 years. Current users were more likely than past users to be male, and also were likely to be somewhat younger. More than 60% of the respondents reported moderate to severe spasticity, pain, and sleep problems.

Phase III study examines cannabinoid agent for MS spasticity

Americans who look to cannabis-based agents for relief of MS symptoms may have a new treatment option – one already offered in more than two dozen other countries – available to them in the years just ahead.

GW Pharmaceuticals and its United States subsidiary, Greenwich Biosciences, on November 3, 2019 announced the initiation of the first United States Phase III clinical trial studying nabiximols for MS-associated spasticity.¹⁷

Nabiximols, which are known as Sativex^® outside of the United States, are approved for treatment of MS spasticity in more than 25 countries. GW Pharmaceuticals, which focuses on the development and commercialization of cannabinoid prescription medicines, said that nabiximols is a complex botanical medicine formulated from extracts of the cannabis plant. It is administered as an oral spray.

The company noted that three European Phase III clinical studies showed that nabiximols was well-tolerated and provided continued reductions in patient-reported spasticity in people with MS. The new Phase III trial is one of five pivotal studies planned for nabiximols in MS spasticity, with the remaining studies on track to begin later this year or in 2021. The company said that it expects that a positive result in any one of the five studies will enable submission of an application for Food and Drug Administration (FDA) approval of the agent, potentially as early as mid-2021.

The Phase III, double-blind, parallel, placebo-controlled study will evaluate the safety and efficacy of nabiximols for spasm frequency over a 12-week period. It is expected to enroll 446 participants.

Evaluating the long-term impact of therapeutic plasma exchange

Therapeutic plasma exchange – the removal and replacement of the plasma component of a person’s blood through the use of a special machine – is an option sometimes employed when high-dose steroid therapy isn’t effective in treating an MS relapse.

A recent study examined the impact of the treatment strategy over 12, 18, and 24 months, and sought to identify whether certain patient characteristics or disease features were associated with a better response to therapeutic plasma exchange (TPE).¹⁸

Researchers analyzed data on 24 people with relapsing-remitting MS who received steroids followed by TPE and 43 patients who received steroids only. Patients in the two groups were matched for age, sex, disease duration, and disability level at the time of the relapse. Good response to treatment was defined as a reduction of at least 50% in one’s Expanded Disability Status Scale (EDSS) score. Initial EDSS scores in the two groups were similar.

While two-thirds of the people receiving TPE initially had a good response to the treatment, the researchers found no significant differences between their EDSS scores and those of the steroid-only patients at 12, 18, or 24 months of follow-up. Further, preliminary analysis did not identify any patient characteristics or disease features associated with a favorable response to TPE.

Although the study did not identify an added long-term benefit from following high-dose steroids with TPE, the fact that most TPE recipients had a good initial response to the therapy is encouraging news, especially considering that up to one-quarter of people experiencing a relapse do not obtain sufficient improvement from steroids alone.

Can taking aspirin as a warm-up help avoid overheating during exercise?

In addition to the time pressures and other deterrents to regular exercise that all people face, many people with MS also have to cope with the exertion-induced overheating that is a frequent feature of multiple sclerosis.

A new study is examining whether taking aspirin before working out can help remove that MS-specific obstacle to maintaining an exercise routine. ASPIRE is a large-scale, double-blind randomized controlled trial that will compare the effects of aspirin with those of acetaminophen (generic version of the brand name Tylenol^®) and placebo in 60 people with MS.¹⁹

Each study participant will engage in three maximal exercise tests, with the evaluations scheduled at one-week intervals. A study subject will take 650 mg of aspirin before one test, a standard dose of acetaminophen before another session, and placebo prior to the third session. The study’s two main endpoints are time to exhaustion and change in body temperature from the pre-exercise period to the immediate post-exercise period. Study organizers note that a pilot trial showed that aspirin pre-treatment increased exercise time and reduced the post-exercise increase in body temperature by 56% in people with MS who experience overheating on exertion.

References
¹⁴ Sharrack B, et al. Autologous stem cell transplantation versus alemtuzumab or ocrelizumab in relapsing remitting multiple sclerosis (StarMS). ECTRIMS 2020 [P0191].

¹⁵ Clene Nanomedicine. September 11, 2020. Clene Nanomedicine Presents Interim Results from REPAIR-MS and REPAIR-PD Phase 2 Studies. Available at https://clene.com/wp-content/uploads/2020/09/Clene-Nanomedicine-REPAIR-MS-MSVirtual-Data-Release-Final-20200910.pdf.

¹⁶ Salter A, et al. Cannabis use among people with MS: A 2020 NARCOMS survey. ECTRIMS 2020 [P00439].

¹⁷ GW Pharmaceuticals. GW Pharmaceuticals initiates pivotal Phase 3 study of nabiximols for multiple sclerosis-associated spasticity. November 3, 2020. Available at: https://www.globenewswire.com/news-release/2020/11/03/2119212/0/en/GW-Pharmaceuticals-Initiates-Pivotal-Phase-3-Study-of-Nabiximols-for-Multiple-Sclerosis-Associated-Spasticity.html.

¹⁸ Marrodan, M, et al. Therapeutic plasma exchange in MS relapses: long term outcome. ECTRIMS 2020 [P0408].

¹⁹ Leavitt V, et al. ASPIRE Study: Protocol for a double-blind RCT of aspirin for overheating during exercise in MS. ECTRIMS 2020 [P0190].

For More Information

For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org.

Written by Tom Garry, Medical Writer

Reviewed by Dr. Barry Hendin, MSAA Chief Medical Officer

Edited by Susan Wells Courtney, MSAA Senior Writer