What’s New in MS Research – May 2024

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

The astounding breadth of research being conducting into the causes, manifestations, and management of multiple sclerosis (MS) was on full display when thousands of physicians, nurses, laboratory scientists, and others gathered in Denver in April for the annual meeting of the American Academy of Neurology (AAN).

The study summaries included in this edition of “What’s New in MS Research” provide a sense of the wide-ranging topics discussed at the annual meeting. We open with intriguing news about indications that anti-diabetic medications in high demand today for their weight-loss effects may also have a role to play in the management of MS.

There also are positive findings on an approved disease-modifying therapy (DMT) and pregnancy, as well as positive findings on an experimental DMT being evaluated for potential use in MS. Other items look at MS and risk for postpartum depression; the impact of discontinuing DMTs; the incidence of cannabis use disorder in people with MS; key differences in late-onset MS relative to adult-onset MS; and more.

For individuals with MS and their family members, the value of these annual meetings and the research presented cannot be overstated. MSAA is pleased to be able to report a sampling of these important meeting highlights to the MS community and we hope that you find these reports to be both informative and encouraging.

Can popular weight-loss drugs reduce MS activity as well as pounds?

Several anti-diabetes agents that drive weight loss may also have a role to play in preventing or managing multiple sclerosis (MS), researchers say. 1

The researchers raised that possibility after examining 19 years of data from a Food and Drug Administration (FDA) database. Their analysis showed an inverse association between MS and the use of metformin, semaglutide (marketed as Ozempic®, Rybelsus®, and Wegovy®), dulaglutide (Trulicity®), and empaglifozin (Jardiance®).

The term “inverse association” means that a greater quantity or rate of one value (in this case, use of the medications mentioned above), is associated with less of something else (in this case, MS activity). It is important to note, however, that the term “association” means only that a pattern has been observed; it does not mean that a cause-and-effect relationship has been established.

No such association was found when the researchers studied other drugs that also are used for weight loss but that do not help control diabetes. These latter agents include phentermine, bupropion, topiramate, and zonisamide.

In discussing the rationale for their research, the investigators noted, “Several studies have demonstrated that early childhood and adolescent obesity are risk factors for MS susceptibility. Obesity is thought to share inflammatory components with MS.”

This inflammation occurs through the overproduction of a certain type of pro-inflammatory cytokine (in this case, an adipokine called “leptin”) and the reduction of a certain type of anti-inflammatory cytokine (in this case, an adipokine called “adiponectin”). Cytokines are small proteins that send signals to help regulate the immune system.

The investigators continue on to explain that while the FDA’s Adverse Event Reporting System contains information that can help identify drug side effects, the system also can be utilized to search for clues that medications approved for one purpose may also be effective in treating other conditions.

The study, while ingenious in its design and encouraging in its findings, remains hypothesis-generating, meaning that it has identified a possibility that now must be evaluated in clinical trials. However, if such studies show a role for these anti-diabetic agents in controlling MS or perhaps even reducing the risk of its development, this research could serve as the foundation for an entirely new approach to managing multiple sclerosis.

More weighty matters: Impact of BMI on B cells counts with Kesimpta®

Americans are contending with an obesity crisis, and people with MS certainly aren’t exempt. Beyond evidence indicating that obesity is a risk factor for developing multiple sclerosis and is associated with worse MS outcomes, clinicians also need to consider whether carrying excess pounds diminishes the efficacy of standard doses of disease-modifying therapies (DMTs).

Researchers examined this question in an analysis of data from the Phase III ASCLEPIOS I and II trials, which evaluated the B-cell depleting therapy Kesimpta® (ofatumumab) relative to Aubagio® (teriflunomide).2 The investigators categorized patients into groups based on body mass index (BMI) and then looked for any significant differences in efficacy measures from one group to another.

The analysis included study subjects who were randomized to receive 20 mg of Kesimpta administered by subcutaneous injection every four weeks (following an initial “loading” dose of three injections given in the first three weeks followed by one week off) and those randomized to take 14 mg of Aubagio orally once daily. The study assessed change in counts of B cells – immune-system cells that have been implicated in the MS disease process – as well as annualized relapse rate (ARR), time to 3 and 6-month confirmed disability worsening (3/6mCDW), the number of gadolinium-enhancing (Gd+) T1 lesions, and annualized rate of new/enlarging T2 lesions (neT2).

The researchers reported that across all BMI categories, patients receiving Kesimpta saw their median B cell counts fall by Week 2 and remain at or near zero cells per microliter for up to 96 weeks. By contrast, they reported, median B cell counts for people receiving Aubagio ranged between 115 to 190 cells per microliter throughout the observation period. Reductions in ARR, 3m/6mCDW, Gd+ T1, and neT2 lesions also favored Kesimpta versus Aubagio across BMI categories, they said.

They concluded, “Monthly 20 mg subcutaneous administration of ofatumumab showed a high degree of efficacy across [people with relapsing forms of multiple sclerosis] independent of BMI, allowing for ease of use with no need of dose-adjustment.”

With recent research showing that 30% or more of people with MS in the United States are obese3, the finding that BMI-based dosage adjustment for one DMT is not needed is welcome news. Understanding the impact, if any, of BMI and weight on other disease-modifying therapies remains an important focus of research efforts.

Study Reports MS therapies are under-utilized, with use varying widely by age

An analysis of insurance claims for tens of thousands of people with MS found that just 57% were receiving a disease-modifying therapy (DMT) in 2021. Further, the proportion of people with MS taking a DMT varied significantly by age, from a high of 64% in people aged 25 to 44 years to 31% among those aged 65 and older.4

In conducting the study, researchers examined information from the MarketScan claims database for the years 2017 through 2021. The database included information on almost 150,000 “person years” of DMT use. As the term suggests, a person year reflects a specific individual’s use of a DMT in a particular year. For example, if the same individual took a DMT in 2018, 2019, and 2020, that would be considered three person years of medication use. The people included in the study had a median age of 51 years, 77% were female, and 72% were commercially insured.

The researchers also found that the use of high-efficacy DMTs increased over the course of the study, so that by 2021, 37% of people aged 18 to 24 years and 7% of people aged 65 years and older were taking a high-efficacy DMT.

The study’s age-related findings may reflect evolving clinical approaches to managing MS. These include a growing interest in exploring whether it is safe to discontinue DMT use as people age, based on the view that the inflammatory component of MS may diminish over the course of many years. Similarly, there is an increasing tendency — supported by several studies – to “start strong” by prescribing high-efficacy DMTs for newly diagnosed people in hopes of quelling inflammation and preventing disease activity that may cause relapses in the short-term and have a negative cumulative effect over time.

While the reasons for age-related differences in DMT use are subject to speculation, the finding that just over half of all people in the study were receiving a disease-modifying therapy would seem to lend itself to a more straightforward conclusion: Given today’s broad array of disease-modifying therapies, far more people with MS could be experiencing the benefits that these DMTs provide.

Understanding the risk of disease activity after discontinuing MS medications

“What are the chances that I’ll have a relapse or see changes on my imaging scans if I stop taking my medication?”

It’s a question that people with multiple sclerosis occasionally ask their clinicians, whether out of a desire for relief from the side effects or costs of therapy or the hope that having gone several years without a relapse means their MS is stable and that it’s safe to discontinue treatment.

Researchers at Brown University and affiliated institutions sought to answer that question by examining the records of 170 people with MS who stopped taking their disease-modifying therapies (DMTs).5 All of the people had visits at the researchers’ center between 2020 to 2023. The average age of the people studied was 60.3 years, and their average Expanded Disability Status Scale (EDSS) score was 3.58, which indicates a moderate degree of disability in one functional area and mild or moderate degrees of disability in other functional areas.

One-third of the people studied stopped their DMT because of side effects and another third stopped at their clinician’s suggestion. Patient preference was the reason cited in 17% of cases, while insurance issues and miscellaneous reasons each accounted for 9% of the treatment discontinuations.

Sixteen percent of the people – or roughly one in six – developed disease activity after stopping their medications. All those patients had magnetic resonance imaging (MRI) findings indicating disease activity, while just under half (13 of 27) had a relapse.

The incidence of disease activity varied by the study participants’ age and by the type of DMT they had been taking. The average age of people experiencing disease activity was 48, while the people with no disease activity had an average age of 60. Meanwhile, the percentage of people with post-discontinuation disease activity varied from 58% of people who stopped Gilenya® (fingolimod) to 13% of those taking B-cell depleting therapies such as Ocrevus® (ocrelizumab).

This research provides intriguing answers to a key question, but its findings must be considered in the light of some caveats and cautions. First, it is a moderately sized study conducted at a single center, which raises the possibility that its results may not be applicable to the overall population of people with MS. Secondly, there is a need to better understand the risk of disease activity at various time points over the long-term, such as within the first year after treatment discontinuation, and after two, three, or more years after stopping therapy.

Most importantly, it should be emphasized that decisions about stopping therapy should be made only in consultation with a clinician and after thoroughly exploring other options. For example, if side effects are driving the desire to stop treatment, a clinician may be able to provide simple approaches for alleviating those issues or to recommend an alternative therapy that will be better tolerated.

Characterizing cannabis use disorder among people with MS

Approximately 20% of people with MS who smoke marijuana or use other cannabis products develop cannabis use disorder (CUD), according to researchers from the NYU Grossman School of Medicine.6

Those researchers recently set out to better understand the characteristics and cannabis-use patterns of people with MS who have CUD, which the Centers for Disease Control and Prevention (CDC) defines as the inability to stop using marijuana even though it is causing health and social problems in a person’s life.

They studied 42 women who had CUD in the context of MS, a positive urine screen for cannabis, and no other substance use disorder. The study participants were selected, based on pre-defined criteria, from among 389 women with MS who responded to advertisements for a clinical trial of a telehealth intervention for CUD.

The average age of the study participants was 42 years. Forty-six percent were white, 34% were Black, and 20% were of mixed or other racial backgrounds. Thirty-nine percent were of Hispanic heritage. The women had an average MS disease duration of 9.7 years. Two-thirds started taking cannabis products after receiving a diagnosis of multiple sclerosis, in keeping with many people’s use of cannabis to relieve MS-related pain and spasticity.

The majority of study participants reported that they used some form of smoking (via marijuana cigarette or pipe) or inhaling via vapes or bongs. One-fifth of the participants reported that edibles were their go-to cannabis product.

The study’s authors noted that their research is important because “cannabis products are used by up to half of all patients living with MS, with only limited symptom benefit, and growing association with the worsening of symptoms such as cognitive dysfunction and depression.” They added that characterizing CUD among people with MS will help shape potential treatment options for the disorder.

Analysis yields disappointing findings on Vitamin D3 supplementation in MS

The 20th Century American essayist HL Mencken wrote, “For every complex problem there is an answer that is clear, simple, and wrong.” A recent meta-analysis suggests that Vitamin D3 supplementation is such an answer to the complex problems posed by multiple sclerosis.

The rationale for Vitamin D3 use is intuitive: Not getting sufficient Vitamin D is a well-established risk factor for developing MS, so it is not unreasonable to think that correcting that deficiency with supplements should have some positive effect on disease course. Except, a group of Brazilian researchers say, there is not significant evidence to support that view.7

Those researchers searched the scientific literature to identify randomized controlled trials that:

  • enrolled people with MS
  • had an intervention group receiving high doses (≥1000 IU/day) of Vitamin D3
  • reported clinical or radiological outcomes

Nine studies with a total of 867 participants met those criteria. Analysis of the results from those studies found no significant reduction in Expanded Disability Status Scale score, annualized relapse rate, or new T2 lesions on magnetic resonance imaging at six to 24 months in people receiving Vitamin D3. The authors noted that their conclusions were in keeping with the findings of other studies examining the impact of Vitamin D3 supplementation. A slight but non-significant reduction of new T2 lesions was observed.

The investigators concluded, “The findings of this meta-analysis strengthen current evidence that vitamin D3 supplementation has no significant impact on clinical outcomes in patients with MS. However, the non-significant reduction of new T2 lesions could precede long-term clinical benefits and should be validated in additional studies.”

Study finds that people with MS are at an increased risk for hoarding

The prevalence of hoarding and cluttering behaviors among people with MS is twice that of the general population, according to researchers who surveyed more than 280 people with MS who received care at the NYU Langone Medical Center.8

The researchers found that 10.4% of those study participants met criteria for clinically significant hoarding or cluttering, while the prevalence of such behaviors in the overall US adult population is about 5%. The study participants had an average age of 44 years and had been diagnosed with MS for an average of 12.7 years. Seventy-one percent were female; 59% were white.

Perhaps not surprisingly, a greater degree of MS severity and higher scores on instruments used to measure hoarding behavior were predictors of increased difficulty in performing activities of daily living due to clutter. One welcome piece of news: Hoarding behavior remained stable among the 118 study participants who completed both a baseline and one-year follow-up survey.

Mental health professionals say that hoarding and cluttering behaviors typically are responses to emotional stress. So if people with MS – or anyone, for that matter – are concerned that they may be engaging in hoarding, getting items to the curb for garbage pick-up may be less important than getting to a psychologist or other counselor to start unpacking the issues underlying the behavior.

MS can be marked by many symptoms – from bowel and bladder control issues to sexual dysfunction – that people may be reluctant to report because of a sense of stigma or shame. Many of those problems, however, can be effectively managed, significantly enhancing quality of life. Hoarding or cluttering behaviors are no different; the crucial first step is to seek help.

Frexalimab shows favorable impact on MS lesions over 48 weeks

More than 90% of people with relapsing MS who took the investigational medication frexalimab did not have gadolinium-enhancing Tesla 1 (Gd+ T1) lesions on magnetic resonance imaging (MRI) after 48 weeks of treatment.9

That finding emerged from the open-label extension period of a Phase II trial conducted to evaluate the efficacy and safety of the monoclonal antibody. Frexalimab blocks the CD40/CD40L pathway, which plays a key role in the activation and function of the immune system.

Frexalimab showed favorable results in the 12-week double-blinded portion of the study, with an 89% reduction relative to placebo in new Gd+ T1 lesions. For that portion of the study, patients were randomized to one of three treatment arms:

  • a higher dose of frexalimab at 1,200 mg, which was administered intravenously every four weeks following an initial loading dose of 1,800 mg
  • a lower dose of frexalimab at 300 mg administered subcutaneously every two weeks, following an initial 600 mg loading dose
  • or placebo.

After 12 weeks, all patients who wanted to, could continue into the open label extension period, along with the people who were in the placebo group and then switched over to frexalimab.

Of the 129 people who completed the 12-week double-blind portion of the study, 125 (97%) chose to go into the open-label extension. The great majority of those study participants – 112 people – remained in the study through Week 48.

Among the people who had received the higher dose of frexalimab for the full 48 weeks, 96% did not have new Gd+ TY1 lesions. Nor did 87% of those who had received the lower dose of frexalimab for 48 weeks. Please note that when all people who received frexalimab, regardless of dose, for 48 weeks were considered together as one group, more than 90% did not have new lesions. Similarly, more than 90% of the people initially randomized to the placebo arm who began frexalimab after Week 12 did not have Gd+ T1 lesions at Week 48.

Researchers added that frexalimab treatment was well-tolerated through Week 48, with nasopharyngitis, headache, and COVID-19 among the most common events seen. They concluded, “Frexalimab continued to show favorable safety and efficacy in [relapsing MS] participants through [Week] 48. These data support its further development as a potential high-efficacy, non-lymphocyte-depleting treatment option in MS.”

Examining how late onset of MS affects function and disability

Do people who develop multiple sclerosis after age 45 have noteworthy differences in the nature and severity of their disease relative to people diagnosed with MS earlier in their adult years? Yes, according to a team of Italian researchers.10

The researchers used several measures to assess 61 people with late-onset multiple sclerosis (LOMS), defined as MS occurring at age 46 years or older, in comparison with 122 people with adult-onset MS (AOMS), defined as being diagnosed from the start of adulthood up to age 45. Both groups were roughly evenly divided between males and females. People in the LOMS group were matched with AOMS group members of the same sex and with similar disease duration.

Compared to their counterparts with adult-onset MS, those in the LOMS group tended to perform worse on the timed 25-foot walk test. They also were more likely to have cognitive impairment and to reach an Expanded Disability Status Scale (EDSS) score of 3.0. Males with late-onset MS also had a greater prevalence of depression compared to men who developed MS earlier in adulthood, with the difference between the two groups being statistically significant.

Interestingly, females with late-onset MS performed significantly worse in tests of visual memory than women with adult-onset MS, but had significantly lower levels of fatigue compared to AOMS females. Within the LOMS group, males had a higher frequency of depression and worse performance in measures of attention than women.

Studies such as this one provide clinicians with valuable insights, not only because the prevalence of late-onset MS is increasing, but also because a better understanding of onset-based and sex-based differences in various manifestations and consequences of multiple sclerosis enables those clinicians to focus their assessments and tailor their management plans to provide highly individualized care.

Multiple sclerosis and the risk for developing post-COVID symptoms

A multi-center study found that people with MS were 1.5 times more likely than other people to develop post-COVID symptoms following coronavirus infection. Having these types of symptoms appearing after the initial infection is referred to as “long COVID.11

The study used an online survey to collect information from 969 people with MS and from 1,003 people without MS who served as a control group. Of those study participants, 613 of the people with MS (63.5%) and 614 controls (61.2%) had confirmed or suspected cases of COVID-19.

Beyond being at increased risk for developing a new COVID symptom 30 days or more after the onset of an acute infection, people with MS also were 3.4 times more likely than the controls to have a worsening post-COVID symptom. The greater risk for both new and worsening symptoms seen in people with MS was statistically significant.

New symptoms seen in the MS patient group included pulmonary and ear, nose, and throat complaints, while the worsening symptoms included musculoskeletal and neuropsychiatric issues. Both new and worsening post-COVID symptoms were associated with subsequently worse MS disability as measured by the Multiple Sclerosis Rating Scale – Revised. The study also found that women with MS were at greater risk than men with MS for post-COVID symptoms.

Researchers noted that identifying and managing long COVID symptoms in people with MS is challenging because “both conditions have similar symptoms, including fatigue, cognitive impairment, weakness, and paresthesia.” They added that the fact that long COVID is associated with greater MS disability highlights “the importance of recognizing and effectively managing [long COVID] in this vulnerable population.”

The finding also underscores the need to talk with a clinician promptly if symptoms linger, appear, or worsen following a bout of COVID.

Reassuring news on women who received Ocrevus® while pregnant

Exposure to Ocrevus® (ocrelizumab) during pregnancy is not associated with an increased risk for miscarriage or for delivering a child with birth defects, according to an analysis of more than 500 pregnancies marked by in utero exposure to the disease-modifying therapy (DMT).12

The Food and Drug Administration (FDA) approved prescribing information for Ocrevus advises women to use contraception while being treated with the medication and for six months after their last infusion of the DMT. Despite that guidance, women have become pregnant while being treated with Ocrevus, which is administered by infusion every six months. Roche, the pharmaceutical company that markets Ocrevus, maintains a safety database that includes information on the outcomes of those women’s pregnancies.

Analysis of 512 pregnancies in which there was in utero exposure to Ocrevus found that:

  • 84.2% culminated in a live birth
  • 7.4% ended in miscarriage (average risk of pregnancy loss in the general population is 15%13)
  • 7.4% were terminated by abortion
  • 0.8% were ectopic pregnancies (average risk of an ectopic pregnancy in the general population is 0.5%14)
  • 0.1% (1 case) resulted in a stillbirth

In addition, the incidence of major birth defects in a larger set of 855 pregnancies marked by Ocrevus exposure was 1.3% (average risk of a birth defect in the general population, minor or major, is 3%15).

The study’s authors note, “In utero exposure to ocrelizumab did not increase the risk of adverse pregnancy or infant outcomes compared with previous reports as well as epidemiological background of both [the] MS and general population[s].”

While these findings are reassuring, the FDA’s guidance that women of reproductive potential should use a reliable form of contraception during Ocrevus treatment and for six months following that treatment, remains both unchanged and important.

MS tied to increased risk for postpartum depression

A recent study found that one in five women with MS experienced depression in the first 12 months after childbirth. 16 The researchers conducting the study noted that this rate is higher than the prevalence of postpartum depression in the overall population of new mothers but in keeping with the findings of earlier studies focused on women with MS.

The researchers analyzed data from the PRISMA registry of women with MS who are pregnant, who are contemplating pregnancy, or who are in the postpartum period. They evaluated information on the first 53 women to participate in the registry, including those women’s scores over time on different surveys validated for detection of depression and anxiety. Seventy-one percent of the women in the study were non-Hispanic and white. The study participants’ median pre-conception Expanded Status Disability Scale (EDSS) score was 1.5, indicating a mild degree of disability.

Among the 19.5% of women who experienced depression at some point in the year following childbirth, the peak incidence was at one month postpartum. However, 78% of women who had depression at the one-month mark saw their mood scores normalize by four months after delivery. Having higher scores on the Edinburgh Postnatal Depression Scale (EPDS) – one of the instruments used to assess the women’s emotional status – correlated with a preconception history of psychiatric disease but did not correlate with clinical relapses in the first three months following childbirth.

The study authors said their research “suggests the need for early evaluation postpartum and integration of neurological, obstetrical, and psychological care.” Their findings also underscore the importance of new mothers with MS being alert to their increased risk for depression and not hesitating to report concerns to their obstetrician, neurologist, or other healthcare provider.


1. Shirani A, Cross A, Stuve O. Inverse association between weight-loss inducing anti-hyperglycemic agents and multiple sclerosis: data mining of the FDA Adverse Event Reporting System Database. AAN 2024. Abstract P11.001.1

2. Cross A, Hauser S, Wiendl H, et al. B-cell depletion and efficacy outcomes of ofatumumab are consistent across different body mass index categories: insights from ASCLEPIOS I and II trials. AAN 2024. Abstract P9.002.

3. Parrotta E, Kister I, Charvet L, et al. COVID-19 outcomes in MS: observational study of early experience from NYU Multiple Sclerosis Comprehensive Care Center. Neurol Neuroimmunol Neuroinflamm. 2020;7:e835.

4. Geiger C, Wang R, Ng C. Variation in the use of disease-modifying therapies in persons with multiple sclerosis by age. AAN 2024. P2.002.

5. Karayi G, Quinones-Herrero N, Martin J, et al. A retrospective analysis of disease modifying drug discontinuation in patients with multiple sclerosis. AAN 2024. Abstract S31.010.

6. Pehel S, Ko T, Fernandez L, et al. Cannabis use disorder in multiple sclerosis: characterization of a national sample of patients seeking treatment. AAN 2024. Abstract P2.006.

7. Oliveira JVMF, Solti M, Apostolos-Pereira S, et al. Vitamin D3 as an add-on treatment for multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials. AAN 2024. Abstract P1.017.

8. Bacon T, Naiman T, Bacon J. Hoarding and cluttering behaviors in multiple sclerosis patients: a longitudinal cohort study. AAN 2024. Abstract P3.010.

9. Giovannoni G, Granziera C, Mao-Draayer Y, et al. Safety and efficacy of frexalimab in relapsing multiple sclerosis: 48-week results from the phase 2 open-label extension. AAN 2024. Abstract S31.007.

10. Tedone N, Preziosa P, Mistri D, et al. Late-onset compared to adult-onset multiple sclerosis: differences in clinical and cognitive profiles and impact of sex. AAN 2024. Abstract P1.004.

11. Son JY, Hu C, McAlpine L, et al. Post-COVID conditions in people with multiple sclerosis: a cross-sectional multicenter study. AAN 2024. Abstract P1.002.

12. Bove R, Pietrasanta C, Oreja-Guevara C, et al. Pregnancy and infant outcomes in females receiving ocrelizumab for the treatment of multiple sclerosis: analysis of over 3,000 pregnancies to date AAN 2024. Abstract S7.004.

13. Medical News Today at Miscarriage rates by week: Risks and statistics (medicalnewstoday.com), accessed 5-20-24

14. Healthline at Ectopic Pregnancy: Symptoms, Causes, and Treatments (healthline.com), accessed 5-20-24.

15. The Centers for Disease Control and Prevention (at Data and Statistics on Birth Defects | Birth Defects | CDC), accessed 5-20-24.

16. Rose M, Hsu S, Balan A, et al. Risk factors for peripartum mood disorders in women with MS: a prospective study. AAN 2024. Abstract P4.014.

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