What’s New in MS Research – March 2023

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

If there is a unifying thread to the studies reported in this edition of “What’s New in MS Research,” it’s “connections.” While the research summarized below addresses topics ranging from postpartum relapse rates to ethnicity-based differences in MS onset, the common theme is identification of links, associations, and relationships that offer new insights into multiple sclerosis and – often – suggest new approaches to its treatment.

The studies, which were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023 in February, include research showing the links between cardiovascular disease and MS outcomes, disease duration and the efficacy of oral disease-modifying therapies (DMTs), as well as gastrointestinal complaints and the subsequent emergence of MS.

Meanwhile, connections of another kind were featured in four studies conducted by the Multiple Sclerosis Association of America (MSAA) and presented at ACTRIMS. Those studies, detailed to follow, highlight the impact of efforts by MSAA to connect people with MS with magnetic resonance imaging (MRI) services and with data that can help them make informed decisions about various DMTs. Other assessments of MSAA activities presented at ACTRIMS detail MSAA’s work to better connect with and meet the needs of the Hispanic/Latinx and the Black and African American MS communities.

Assessing how disease duration affects the efficacy of infused and oral MS therapies

Infused disease-modifying therapies (DMTs) for multiple sclerosis generally are considered to have greater efficacy than oral DMTs, but what is the degree, if any, of that difference, and how does the duration of a person’s MS come into play? Researchers with the Rocky Mountain MS Center at the University of Colorado sought to answer those questions in a study of 1,044 people with relapsing-remitting MS. The study subjects included 509 people who took an oral DMT and 495 who received an infused therapy. MS duration was similar between the groups, at an average 10.15 years for people on oral therapy and 10.67 years for those receiving an infused medication.1

The researchers compared the two groups in terms of disease activity, which was defined as having a clinical relapse or developing a new lesion identified with the T2 methodology or gadolinium-enhancement on magnetic resonance imaging (MRI).

In the full study population, 36.4% of those on an oral therapy experienced disease activity, as compared to 21.2% of those receiving an infused medication. When researchers went a step further and analyzed results by disease duration, several interesting findings emerged:

  • Among patients taking oral DMTs, those who had experienced MS for 12 years or less were roughly twice as likely as those with longer disease duration to have overall disease activity and new T2 lesions
  • Among patients receiving infused medications, there was no significant difference in disease activity based on whether they had experienced MS for 12 or fewer years or for more than 12 years
  • In people with a disease duration of 12 years or less, those taking oral therapies were 2.7 times more likely than people on infused medications to experience disease activity
  • Among people with a disease duration of more than 12 years, people on oral medications were just 1.12 times more likely than infusion-therapy patients to have disease activity.

These findings may help inform decisions about how to tailor a person’s treatment regimen over time. In the study, infused therapies demonstrated greater efficacy than oral DMTs in the first 12 years of people’s disease course, but the extent of that advantage declined after the 12-year mark. Because higher-efficacy DMTs often are associated with more frequent or more significant side effects, this study may lend new support to “de-escalation” strategies, in which people with MS shift from higher-efficacy to moderate-efficacy therapies as they age to minimize the risk of adverse effects.

Positive reviews for MSAA’s “Ultimate MS Treatment Guide”

With more than 20 disease-modifying therapies (DMTs) approved by the Food and Drug Administration (FDA) for MS, treatment decision-making has never been more complex. It’s a good – even great – problem to have, of course, because it enables people with MS and their clinicians to individualize therapeutic strategies to optimal effect, but it poses challenges nonetheless.

To help people with MS sort through the options and understand the characteristics of each therapy, the Multiple Sclerosis Association of America (MSAA) developed the Ultimate MS Treatment Guide. This interactive guide provides detailed information on each FDA-approved medication, including a patient-friendly description of how the medication works, and allows users to compare up to three different therapies at a time. The guide also incorporates video clips of healthcare professionals sharing their clinical perspectives and patient advocates discussing their firsthand experiences.

Since its release in August 2022, the Ultimate MS Treatment Guide has had more than 79,000 pageviews. To identify ways to further enhance the site, MSAA recently surveyed 399 users. Key findings include:

  • 94% of respondents felt the tool would help in shared decision-making with their doctor in learning about and selecting a DMT
  • 92% reported feeling that the tool would either likely or definitely improve communication about their MS-treatment plan with their healthcare team and with family members
  • 85% reported finding the Ultimate MS Treatment Guide helpful or extremely helpful in learning about different FDA-approved DMTs2

MSAA will continue to adapt the Ultimate MS Treatment Guide based on feedback from users and as new therapies are approved by the FDA.

To view the Ultimate MS Treatment Guide, please visit MStreatmentguide.org.

Support for re-starting disease-modifying therapy soon after delivering

Resuming disease-modifying therapy (DMT) shortly after giving birth reduces the risk of moderate/severe postpartum relapses by more than 50%, according to a recent study involving 994 women with MS.3

The retrospective study drew on healthcare insurance claims data to examine patterns of relapse in women, all of whom had been exposed to DMTs before or during their pregnancies. Researchers defined a moderate/severe relapse as an MS-related hospitalization or outpatient visit that was accompanied by a healthcare claim for steroids or total plasma exchange prescribed within seven days of the hospital admission or visit.

The researchers found that the incidence of relapses declined during pregnancy, with 8.2% of study participants experiencing a relapse in the period prior to pregnancy as compared to 1.2% in the first trimester, 0.9% in the second trimester, and 1.1% in the third trimester. However, the relapse rates increased after delivery, with 6.5% of women having a moderate/severe relapse at 0-3 months postpartum and 5.4% experiencing a relapse in months 4-6 postpartum.

More than 90% of the study subjects stopped taking their DMT during pregnancy. Among those women, only 5.2% who resumed their DMT postpartum experienced a relapse in the six months after delivery, compared with 10.2% of women who did not start taking their DMT again.

The study’s authors concluded that their findings “support a role for early re-initiation of DMT postpartum.”

Exploring the link between cardiovascular disease and MS progression

Diminished cardiovascular health and accelerated MS disability go hand-in-hand, according to the findings of a recently reported study.4

Researchers followed 276 people over an average of 14.9 years. Among the study subjects, 129 had relapsing-remitting MS at baseline, 117 had a progressive form of MS, and 29 had clinically isolated syndrome.

Two-thirds of the study participants – or 183 people – received a new diagnosis of high blood pressure, high lipids, diabetes, or heart disease during the follow-up period. On average, those people experienced confirmed progression of MS-related disability at 13.4 years, as compared to 15.2 years for the 93 study subjects with no new cardiovascular disease (CVD) diagnoses during the follow-up period. The difference, which was determined by changes in Expanded Disability Status Scale (EDSS) scores, was statistically significant.

The researchers did not find any sex-related differences in the impact that a new CVD diagnosis had on MS-disability progression. They did, however, find that identification of cardiovascular disease in older people with MS had a greater impact on EDSS scores than it did in younger people.

It is important to note that this study discovered an association between CVD and MS-related disability rather than establishing a direct cause-and-effect relationship or uncovering the physiological mechanisms that might drive such a relationship. Nonetheless, the fact that two-thirds of study subjects developed cardiovascular disease over a 15-year period underscores the importance of attending to overall health while also working to manage one’s MS.

Obesity in people with MS: Common and a contributor to worse outcomes

A recent study of U.S. residents with MS found that 70.3% were overweight or obese at diagnosis, and that this proportion of overweight/obese patients increased to 73.7% within about two years after diagnosis.5

Conducted by researchers from the Cleveland Clinic and Case Western Reserve University, the study focused on 949 people whose body mass index (BMI) and other data were available in a multi-institutional registry. The study subjects’ mean age at baseline BMI measurement was 39.8 years; 71% of the people studied were female.

The study participants’ average BMI at baseline was 29.7 kg/m2, just below the 30 kg/m2 threshold for obesity. After an average follow-up period of 2.1 years, that average inched across the obesity threshold to 30.1.

The proportions of subjects in different BMI categories at baseline and follow-up were:

  • Underweight: 1.4% at baseline and 1.5% at follow-up
  • Normal weight: 28.2% and 24.9%
  • Overweight: 27.9% and 29.5%
  • Obese: 42.4% and 44.2%
  • Women were more likely than men to see their BMI increase by 2 kg/m2 or more during the follow-up period. Meanwhile, each year of education that a person reported decreased the odds of such weight gain by 11%.

“Women and the less-educated may need careful weight monitoring due to higher odds of accelerated weight gain,” concluded the researchers, who noted that obesity predisposes people to cardiovascular conditions and a pro-inflammatory state, both of which can adversely affect MS disease course.

Elevated risk for GI issues in the years before MS onset

In the five years prior to their first demyelinating event or MS symptom, people with multiple sclerosis are more likely than people of the same age and sex to experience gastrointestinal (GI) problems, according to a team of Canadian researchers.6

The researchers identified more than 7,500 people with MS and matched them by age, sex, and geographic region with more than 36,000 “controls,” or people who do not have MS. Then, focusing on the five-year period before a person with MS had a first demyelinating event or multiple sclerosis symptom, the researchers compared the two groups in terms of GI-related doctor visits and prescriptions.

The people who later would be recognized as having MS were 1.42 times more likely than the control group to see a physician for gastritis or duodenitis – two common gastrointestinal complaints – and 1.46 times more likely to visit a doctor for diseases of the esophagus. Similarly, people with MS were more than twice as likely as controls to receive a drug for constipation and almost twice as likely to receive a drug for nausea or to prevent vomiting in the years before an MS diagnosis.

These findings led the researchers to conclude that, “GI symptoms appear to be part of the MS prodrome” or constellation of signs and symptoms often present before the onset of a disease. Of course, gastrointestinal symptoms are quite common, and the great majority of people who experience them will not go on to develop MS. However, the identification of an increased rate of GI symptoms in people who subsequently are found to have MS contributes to investigators’ understanding of the disease and may inform research to further unravel the factors contributing to development of multiple sclerosis.

Making imaging accessible to people with MS: Gauging the impact of an MSAA initiative

Magnetic resonance imaging (MRI) is a powerful tool for diagnosing MS, tracking the course of the disease, and assessing response to treatment. Too often, however, people with MS face challenges obtaining clinician-recommended MRIs because of financial issues.

To help overcome that obstacle, the Multiple Sclerosis Association of America (MSAA) established its MRI Access Program. The program provides funding for an MRI to individuals who meet certain household income requirements, who do not have medical insurance or who are not able to afford MRI-related insurance costs such as co-pays and deductibles, and whose physician has certified that a cranial or spinal MRI is needed to diagnose MS or evaluate disease progression. Because of demand for the program’s services, participants cannot exceed one MSAA-funded MRI every 24 months. Research presented at this year’s annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) detailed the difference the program is making in people’s lives.7

Two MSAA staff members analyzed quantitative and qualitative data on 1,291 people who participated in the program over a recent 12-month period. The group included 977 females, 308 males, and one non-binary person. Sixty-five percent of the people were White/Caucasian, 17% were Black/African American, 10% were Hispanic/Latino, 1% were Asian/Pacific Islander, and the remainder identified as other, cited one or more races, or preferred not to answer the question. Sixty percent had a family income of $50,000 or less and – in keeping with MSAA’s criteria for program participation – none had income that was more than 300% of the federal “poverty line.” All participants were uninsured, underinsured, or facing financial challenges that precluded them from being able to afford the co-pay and co-insurance for an MRI.

In terms of the impact that the MSAA MRI Access Program had on participants:

  • 92% said the program was very helpful in better managing their MS
  • 74% remained on their current therapy based on MRI results, while 10% began a new therapy and
  • 16% switched therapies
  • 40% reported making lifestyle adjustments to better manage their MS
  • 28% reported sharing the resource with others in the MS community
  • 23% reported becoming more active in monitoring their MS
  • 20% began to treat or manage an MS symptom

The qualitative feedback reported in the study provided a human dimension to those statistics. Two physicians from Kentucky wrote, “MRIs are vital in the treatment of MS, and to many of our patients, the cost of the MRI or the co-pay is a barrier that keeps them from receiving the care they need. The value you provide goes far beyond the MRI – you bring a personal comfort with every approval.”

To learn more about MSAA’s MRI Access Program, the only nationwide initiative of its kind for the MS community, please visit https://mymsaa.org/msaa-help/mri/.

Study ties Hispanic ethnicity to younger age at diagnosis of MS

A study involving more than 800 people with MS found that those who identify as Hispanic were diagnosed at an average age four years younger than that of White/non-Hispanic people.8

Researchers from the Icahn School of Medicine at Mount Sinai in New York City conducted the study by reviewing records on 830 consecutive patients aged 64 years or younger who were diagnosed with relapse-onset MS after 2000 and who received care at their outpatient clinic between 2018 and 2021. They found that people who identified as Hispanic were diagnosed at an average age of 31.8 years, as compared to 35.9 years for White/non-Hispanic people and 34.8 years for Black/non-Hispanic people.

Further, 9.6% of Hispanic patients were diagnosed with MS before age 20, while only 3.7% of White/non-Hispanic and 3.7% of Black/non-Hispanic patients were identified as having MS before 20 years of age.

Hispanic patients also reported a greater degree of MS-related disability than other patients, with scores of patient-reported assessments of overall physical health and gait problems showing that Hispanic people reached disability milestones sooner than non-Hispanic patients. In analyzing those scores, researchers found that this greater disability accumulation appears to reflect degree of disability for a person’s age, rather than for years since diagnosis.

The study’s authors called for further research “to better understand underlying mechanisms of earlier MS onset (and greater risk for pediatric onset) among persons with Hispanic ethnicity, which may inform understanding of MS pathogenesis more generally.”

Enhancing advocacy and education for the Hispanic/Latinx MS community

Helping people with MS understand their condition requires first understanding those specific individuals, including their culture, experiences, priorities, and preferences.

In order to enhance its patient advocacy and educational efforts on behalf of the Hispanic and Latinx MS community, the Multiple Sclerosis Association of America (MSAA) conducted two virtual advisory board meetings with 18 healthcare professionals and patient advocates. Specific objectives of MSAA’s Hispanic and Latinx Advisory Board (HLAB) were to contextualize the experience of members of the Hispanic and Latinx community; identify barriers that community members face and ways to address educational gaps and lack of needed support; and obtain feedback on the design and implementation of educational programming and clinical advocacy relevant to the Hispanic and Latinx community.9

Advisory board members noted that systemic barriers faced by the Hispanic and Latinx MS community include access to healthcare, cultural barriers, language hurdles, stigma, socioeconomic status, legal status, mobility/jobs, and access to health literacy.

Meeting participants also recommended that educational resources for the Hispanic/Latinx MS community should be marked by:

  • cultural competence
  • community collaboration
  • a focus on health literacy, with provision of bilingual resources

They also called for cultural awareness education for healthcare professionals.

MSAA published a white paper summarizing the advisors’ discussions and is moving forward with several steps to better serve the Hispanic/Latinx MS community, including offering bilingual webcasts on topics such as finding resilience in living with MS.

Charting a course to meet the needs of Black and African American people with MS

The race-based inequities that have adversely affected Black people and African Americans in all aspects of healthcare are exacerbated by a longstanding misperception when it comes to multiple sclerosis. Specifically, the conventional wisdom has held that while Black people often have faster disease progression than White people, the incidence of MS in the Black and African American community is much lower than that in other racial and ethnic groups. Unfortunately, the first premise is correct and the second is incorrect; in addition to tending to have more-rapid disease progression, incidence rates of MS is actually higher in Black Americans than White Americans.

To help address the healthcare disparities and heightened disease incidence and severity experienced by Black and African American people, the Multiple Sclerosis Association of America (MSAA) invited neurologists, nurses, patient advocates, and care partners to participate in its African American Advisory Board. Those advisory board members shared their experiences, views, and recommendations in two, 2-hour virtual meetings held in August 2022.

As reported at the 2023 annual meetings of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), those discussions emphasized the need for clinical research and the importance of creating programmatic initiatives and interventions tailored specifically to the needs of the African American and Black community. Priorities identified at the meetings included:

  • provider education, such as continuing medical education courses
  • a multi-stakeholder meeting
  • patient education programs10

Following up on the advisory board’s recommendations, MSAA has partnered with Impact Education, LLC and the Postgraduate Institute of Medicine to launch a multifaceted intervention including patient-education and clinician-focused programs. More than 90% of participants in the patient-focused programs found those offerings to be helpful and more than 80% of clinicians participating in programs for healthcare professionals said they planned to implement changes in their practices based on the information presented and/or that their current practice has been reinforced by information shared at the programs.

Mavenclad® (cladribine) and cognitive function in highly active relapsing MS

People with highly active relapsing MS who received the oral disease-modifying therapy (DMT) Mavenclad® (cladribine) had stable cognitive function over two years of treatment, according to a recent study.11

The study involved 399 people, all of whom were identified as having highly active MS, which can adversely affect cognitive functions such as processing speed, learning, and memory. Roughly three-quarters of study participants – 291 people – had been treated with another DMT before starting Mavenclad, while the remaining 108 people had not received a prior DMT before beginning Mavenclad therapy.

Study participants completed the Brief Cognitive Assessment for Multiple Sclerosis (BICAMS) battery of assessments when they began the study and then again at Month 12 and Month 24. Researchers reported the results of the assessments as scaled scores, with better performance reflected by higher scores.

Scores on the Symbol Digit Modalities Test – a component of the BICAMS battery that measures processing speed and motor speed – showed no absolute change from baseline to Month 12 and Month 24. Meanwhile, scaled scores of other BICAMS components that evaluate learning and memory increased slightly from baseline to Month 12, with those modest gains maintained through Month 24.

Researchers reported that test performance did not differ significantly between people who had taken another DMT before starting Mavenclad and those taking Mavenclad as their first DMT. Further, the investigators did not find any correlation between changes in BICAMS assessments and changes in patients’ brain volume as measured by magnetic resonance imaging.

Disappointing findings on high-dose Vitamin D and imaging markers of disease activity

Vitamin D insufficiency is a risk factor for developing MS and for relapses, but can high-dose Vitamin D3 supplementation reduce disease activity in relapsing-remitting MS? No, according to results from the Phase III Vitamin D to Ameliorate MS (VIDAMS) trial.12

The study, which was conducted at 16 neurology clinics across the United States, enrolled people ages 18 to 50 with relapsing-remitting multiple sclerosis (RRMS) and recent disease activity. Study subjects were started on the disease-modifying therapy glatiramer acetate and then randomized to receive either low-dose (600 International Units per day) or high-dose (5,000 International Units/Day) Vitamin D3. Researchers monitored study participants for up to 96 weeks. The trial’s primary endpoint focused on clinical relapses. In addition, magnetic resonance imaging (MRI) was performed annually to assess changes in brain volume and lesion volume, to look for new or enlarged lesions, and to assess other indicators of disease activity.

While the study did not meet its primary endpoint of reducing the risk of clinical relapse, further analysis was conducted to see whether adding high-dose Vitamin D3 to glatiramer acetate therapy might at least show a benefit in terms of imaging markers of disease activity. Unfortunately, in analyzing data on 139 study participants, researchers found that the low-dose and high-dose groups had similar rates of changes in various brain-volume measurements. They also found no differences between the groups in terms of lesion development or enlargement.

Negative study results are always disappointing, but they nonetheless advance the search for effective interventions by enabling researchers to shift focus to other interventions that, hopefully, will yield better results.


1 Vollmer B, Nair K, Sillau S, Corboy JR, Alvarez E. Examining the effect of disease duration in high-efficacy versus mid-efficacy disease modifying therapies: Could this inform when to de-escalate? P163. ACTRIMS 2023.

2 Montague A, Kline A, Durack K. The MSAA Ultimate MS Treatment Guide. P285. ACTRIMS 2023.

3 Bove R, Applebee A, Bawden KM, et al. Postpartum relapse patterns among multiple sclerosis patients with exposure to disease modifying therapy before or during pregnancy. P481. ACTRIMS 2023.

4 Wicks TR, Jakimovski D, Reeves J, et al. Cardiovascular disease diagnosis is associated with long-term confirmed disability progression in multiple sclerosis. P096. ACTRIMS 2023.

5 Conway DS, Toljan K, Briggs F, et al. Body mass index trends in newly diagnosed patients with multiple sclerosis. P094. ACTRIMS 2023.

6 Yusuf F, Zhu F, Evans C, et al. Gastrointestinal conditions in the multiple sclerosis prodrome. P183. ACTRIMS 2023.

7 Kline A, Barnhill M. Multiple Sclerosis Association of America’s MRI Access Program. P452. ACTRIMS 2023.

8 Sumowski JF, Fabian M, Satyanarayan S, Katz Sand I. Hispanic ethnicity is linked to younger age of MS diagnosis and disability accumulation. P184. ACTRIMS 2023.

9 Rivera Bobadilla Y, Kline A. Integrating cultural competence and community collaboration in the design of patient education resources: a framework to reach better health outcomes and decrease health disparities for the Hispanic and Latinx MS community. P449. ACTRIMS 2023.

10 LeGrand M. MS in the African American and Black community. P451. ACTRIMS 2023.

11 Langdon D, Brochet B, Havrdova EK, et al. Stabilization of cognitive function in patients with highly active relapsing multiple sclerosis treated with cladribine during the 2-year CLARIFY-MS study. P090. ACTRIMS 2023.

12 Cassard SD, Fitzgerald KC, Azevedo CJ, et al. High-dose Vitamin D3 supplementation does not reduce imaging measures of disease activity in relapsing-remitting multiple sclerosis in a randomized controlled trial. P079. ACTRIMS 2023.

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