What’s New in MS Research – July 2024

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

 

It wasn’t just the music that had multiple sclerosis (MS) researchers, clinicians, and advocates in an upbeat mood when they gathered in Nashville from May 29th through June 1st for the Consortium of Multiple Sclerosis Centers’ (CMSC) 2024 Annual Meeting. Rather, the positive vibes reflected the many encouraging developments in MS research reported during the CMSC’s multi-day gathering.

With regard to this important meeting, none of this would be possible without the dedication and forward-thinking work of CMSC Founder and CEO June Halper. Sadly, June passed away this month, but her enormous contributions to the care of MS patients will continue to benefit the health and well-being of countless individuals affected by MS.

This edition of “What’s New in MS Research” spotlights several of those advances, including encouraging news on a disease-modifying therapy being evaluated for use in primary-progressive MS as well as the role of pharmacists in helping to prevent falls in people with MS. Other items examine MS in Southeast Asian Americans, risk factors for relapse in secondary-progressive MS, the experience of Black and Hispanic people treated with Ocrevus^® (ocrelizumab), and establishment of a biorepository that already is serving as an engine propelling MS research forward.

For all of the progress being made, however, people with MS still have many unmet needs and face significant barriers to accessing care. A Multiple Sclerosis Association of America (MSAA) study presented at the CMSC Annual Meeting and reported in this article, details many of those needs and barriers. We at MSAA are committed not only to identifying those challenges but also to providing solutions to them.

 

Glatiramer acetate for primary-progressive MS: Encouraging interim study findings

Almost three quarters of people with primary-progressive multiple sclerosis (PPMS) treated with monthly injections of extended-release glatiramer acetate had no evidence of disease progression over 12 weeks, according to interim findings from an ongoing three-year study.¹

The Phase IIa study is assessing the efficacy and safety of a 40-mg dose and 25-mg dose of the disease-modifying therapy (DMT). In reporting data collected to date on 30 adults with PPMS, researchers said that 72.4% of study participants (68.4% receiving the 40-mg dose and 80% receiving the 25-mg dose) showed no evidence of progression (NEP). The study defines NEP as the absence of:

 

• 12-week confirmed disability progression (absent for 96.6% of study subjects)
• 12-week timed 25-foot walk progression (absent for 79.3%)
• 12-week progression in the 9-hole peg test (absent for 93.1%), a measure of manual dexterity
  

 

The investigators added that an analysis of magnetic resonance imaging (MRI) results – looking at new and enlarging lesions – indicated low MRI activity.

The researchers said that most adverse events (AEs) seen to date have been mild, with injection-site reactions being the most commonly reported event and no unexpected AEs reported. They noted that a lower rate of side effects was seen in the 25-mg dose group than in the 40-mg dose cohort. Three serious AEs were reported in the 40-mg group, with one potentially related to the study drug.

Between 10% to 15% of people with multiple sclerosis have PPMS, which is marked by a continuous decline in neurological function without early relapses or remissions. In March 2017, Ocrevus^® (ocrelizumab) became the first DMT approved for the treatment of PPMS. More than seven years later, it remains the only DMT with Food and Drug Administration approval for use in the condition. However, several other potential therapies are in late stages of evaluation for treatment of PPMS, including extended-release glatiramer acetate.

While it is important to note that these are interim findings from a relatively small study, they are nonetheless encouraging and reflect the advances being made in developing additional therapies for primary-progressive MS.

 

MSAA survey defines barriers to care and unmet needs in MS

What are the biggest barriers to care faced by people with MS? The Multiple Sclerosis Association of America (MSAA) recently asked that question (and others) in a nationwide survey. Of the 620 people who responded:

 

• 35% were unable to afford medical care
• 33% were unable to find MS care in their community
• 31% had difficulty finding doctors to coordinate their MS care
• 20% lacked health insurance
• 19% did not have access to transportation²
  

 

Given those findings, it is perhaps not surprising – though still distressing – that 42% of respondents reported not seeing a multiple sclerosis specialist to manage their MS. Further, 43% said they were not able to work due to disability from MS.

The survey participants were ages 18 years and older. Nearly 70% reported living with MS for 11 to 20 years or more. More than 380 expressed their willingness to share more information and insights about their experiences and barriers to care in focus groups.

In presenting these findings at the CMSC 2024 Annual Meeting, the study’s authors explained, “Demographics, socio-economic status, age, race, ethnicity, and community play a significant role in the ability to access resources and healthcare. A thematic analysis of the data collected will be used to identify unmet needs that are unique and specific to given geographic areas and to bring together a diverse group of stakeholders distinct to that ecosystem to engage in dialogue and community collaboration.”

The end goal of the initiative, they added, is to “design personalized and targeted interventions to serve these MS communities.”

 

Identifying risk factors for relapse in secondary-progressive MS

If not taking a disease-modifying treatment, most people with relapsing-remitting multiple sclerosis (RRMS) will eventually transition to secondary-progressive multiple sclerosis (SPMS), but not all of them will experience relapses after that transition. What factors make relapses more likely in SPMS? A team of researchers analyzed the medical records of 192 people with RRMS to help answer that question.³

In this analysis, 94% of the people transitioned to SPMS. Those people had a median disease duration of 13 years. The good news, however, is that at the end of the study, 88% percent of the people who transitioned had not experienced relapses during the prior two years.

Compared to the 12% of SPMS patients who did experience relapses prior to transitioning, the relapse-free people tended to be older when they transitioned to SPMS (in particular, age 40 years or older), and to have had a longer average disease duration (13.6 years vs. 10.8 years), and lower average Expanded Disability Status Scale score (3.4 vs. 4.5) at the time of transition. In addition, those who did not experience relapses after transitioning, also experienced fewer relapses in the two years after MS onset and in the two years prior to SPMS transition (as noted earlier), compared to those who did experience relapses after transitioning. All of those differences were statistically significant.

Pointing to the fact that the overwhelming majority of people who transitioned to SPMS did so without having relapses, the study’s authors concluded, “These data support the emerging view that smoldering inflammatory processes drive disability accumulation independent of relapse activity across the spectrum of MS.” The findings also provide valuable insights into which people with RRMS may continue to experience relapses after moving to SPMS, an important consideration for patients and clinicians to weigh when making decisions about treatment choices and overall care.

 

A BIG step forward in MS research

Researchers at Stanford University are building a biorepository of blood, cerebrospinal fluid (CSF), and stool from people with MS and related neuroimmune diseases that will enable scientists to conduct a wide variety of studies into those conditions.⁴

Termed the “Project BIG” biorepository, the initiative already has collected specimens from 491 people. Of that group, 64% have MS, while other participants have conditions including myelin oligodendrocyte glycoprotein antibody-associated disease, neuromyelitis optica, transverse myelitis, and autoimmune encephalitis.

Participants provide multiple samples over time, with an effort made to collect specimens at key points, such as when experiencing a relapse or changing disease-modifying therapies. The research value of the specimens is enhanced by recording patients’ assessment of pain, fatigue, quality of life, anxiety/depression, and sleepiness at the time of sample collection, enabling investigators to look for correlations between findings from specimen analysis and concurrent symptoms.

The biorepository already has played a role in nine research collaborations, three of which resulted in articles being published in prominent scientific journals, including Nature and Science.

In outlining their work to date at the CMSC’s 2024 Annual Meeting, the project’s leaders noted, “By creating a multidisciplinary biorepository with multi-modal clinical correlates and time-associated PROs [patient-reported outcomes], the ‘Project BIG’ initiative has shown promise in progressing MS research.”

By providing investigators with access to biological samples and accompanying information on patients’ status at the time of sample collection, ambitious initiatives such as Project BIG hopefully will enable recognition of patterns and connections that can guide development of effective therapies and approaches to overall patient management.

 

Encouraging one-year findings on Ocrevus^® in Black and Hispanic people with relapsing MS

More than 94% of Black and Hispanic people with relapsing MS had no relapses and no 24-week confirmed disability progression (CDP) following one year of treatment with Ocrevus^® (ocrelizumab).⁵

That was one of the main findings to emerge from the CHIMES trial, a prospective, open-label, single-arm study examining the impact of Ocrevus in Black/African-American and Hispanic/Latinx people with relapsing forms of MS. Approved for use in both relapsing MS and primary-progressive MS, Ocrevus is a disease-modifying therapy (DMT) that depletes B cells, which are immune cells that play a role in the MS disease process. After starting therapy with two 300-mg infusions two weeks apart, patients receive a 600-mg dose of Ocrevus every 24 weeks.

The analysis examined data on 113 Black people and 69 Hispanic people. Seventy-three percent were female. The average age of the people studied was 35.5 years, and the average time since diagnosis was 4.5 years. The average baseline Expanded Disability Status Scale (EDSS) score of study participants was 2.4, indicating a mild or modest degree of disability on the scale, which runs from 1 to 10.

The study’s primary endpoint was no evidence of disease activity (NEDA) at 48 weeks. NEDA was defined as the proportion of study participants who had no relapses, no 24-week confirmed disability progression (CDP), and no T1 gadolinium-enhancing lesions [Gd+L] or new/enlarging T2 lesions [NET2Ls]. Forty-six percent of Black study participants and 58% of Hispanic study participants achieved 48-week NEDA. As noted, more than 94% had no relapses or 24-week CDP. Similarly, more than 94% had no Gd+L. However, 54% of Black study participants and roughly 36% of Hispanic study participants had NET2Ls.

No deaths occurred during the study. Eighty percent of participants had one or more adverse events, with 5.5% having one or more serious adverse events. Twenty-nine percent of people had infusion-related reactions. Study participants also showed improvement from baseline in measures of work absenteeism, presenteeism (working while sick), and work productivity.

The ongoing Phase IV CHIMES study is the first trial of its kind to focus on the impact of a DMT specifically in Black and Hispanic people with MS. The research is particularly important because while Black and Hispanic people traditionally have been understudied in MS clinical trials, there are indications that they may have a higher incidence of multiple sclerosis, faster disease progression, and a greater risk for disability progression than White people.

 

Examining MS in Southeast Asian Americans relative to Black and White Americans

For too long, much of what was known or believed about MS was based on studies made up primarily or even exclusively of non-Hispanic White people. Recent efforts, such as the CHIMES trial discussed above, have sought to remedy that imbalance by focusing on the experience of Black and Hispanic people.

In a further step toward better understanding the potential impact of race and ethnicity on MS, three investigators recently analyzed data on 40 Southeast Asian Americans of Indian subcontinent descent, comparing those people’s disease course with that of 40 age-matched White people and 40 age-matched Black people with MS.⁶

Key characteristics of people in each group are as follows:

	Southeast Asian Americans (n = 40)	Black Americans (n = 40)	White Americans (n = 40)
Average age at diagnosis, years	31.2	29.9	28.6
Males/females	8/32	7/33	14/26
Mean Expanded Disability Status Scale (EDSS) score	1.74	2.11	1.76
Mean Vitamin D level, ng/mL	26.84	26.21	29.68

 

In keeping with the data in the table, the authors observed that the Southeast Asian American people had a degree of disability – as measured by the EDSS – similar to that of White people but Vitamin D levels comparable to those of the Black people studied. “We propose to analyze a larger number of patients to better discern the similarities and differences,” they stated in their conclusion, adding, “Studies like ours will help us better understand MS in different ethnic groups.”

If there is one universal truth in MS care, it is that one size does not fit all. By studying issues such as disease presentation, disease course, and response to treatment in people of different backgrounds, researchers will be able to determine what impact race and ethnicity have on MS, as well as the relative importance of those factors compared to considerations such as age, gender, overall health and comorbidities, as well as diet and lifestyle. Taken together, these data points will enable clinicians to tailor highly individualized care plans and treat people for optimal effect.

 

Examining why people switch their disease-modifying therapy

Worsening MS, doctor recommendations, and side effects, are the three most common reasons for switching from one disease-modifying therapy (DMT) to another, according to a survey of more than 300 people with MS.⁷

Seventy-one percent of the survey’s 303 respondents said they had switched DMTs at some point in the course of their MS. And when they did make a change, effectiveness and safety were the top factors guiding their choice of a new therapy, with route of administration, out-of-pocket costs, and side effects also cited as important considerations.

Eighty-two percent of survey respondents reported having used a patient support program offered by a DMT manufacturer. Survey participants (all of whom were members of the iConquer MS research network) said that payment assistance was the most helpful type of patient support offered by pharmaceutical companies.

 

Taking a deep dive into two specific DMT switches

Beyond identifying the reasons that people with MS change disease-modifying therapies (DMTs) generally, as examined above, it is also important to understand why people switch from one particular DMT or type of DMT to another and what that shift entails. Research presented at the CMSC 2024 Annual Meeting examined those issues in terms of people moving from anti-CD20 therapies to Mavenclad^® (cladribine) and from Tysabri^® (natalizumab) to oral DMTS.

The first of those studies was a retrospective analysis in which neurology clinicians provided de-identified information on 100 people with MS who had switched from Ocrevus^® (ocrelizumab), Kesimpta^® (ofatumumab), or other therapies that target the CD20 protein on the surface of the immune system’s B cells to Mavenclad, an oral DMT.⁸

The patients who transitioned to Mavenclad had an average age of 47 years; 70% were female. The most common reasons for stopping anti-CD20 therapies were relapses (41%) and continued clinical activity (26%). Reasons cited for choosing Mavenclad as their new DMT included perception of increased efficacy against relapses (55%) and against disability progression (54%).

Other reasons included a desire to avoid long-term immunosuppression with anti-CD20 therapy (33%) and preference for the short-course dosing of Mavenclad (17%). Although these are among the most commonly reported adverse events when taking an anti-CD20 therapy, no cases of opportunistic infections, reductions in immunoglobulins, or significant reduction in lymphocytes – white blood cells that help protect the body from infection – were reported after the switch to Mavenclad. This study focused on the reasons for switching from an anti-CD20 therapy to another DMT (Mavenclad) and the adverse events experienced after the change. Clinical outcomes, such as the number of relapses experienced after switching DMTs, were not included in the study design.

The second study assessed the experiences of 112 people with MS who had been stable on treatment with Tysabri before switching to moderate-efficacy oral DMTs.⁹

Tysabri is a high-efficacy DMT administered by intravenous infusion. Unfortunately, the medication increases the risk of developing progressive multifocal leukoencephalopathy (PML), a rare brain infection that usually leads to death or severe disability.¹⁰ While that risk is small, it increases with prolonged use of Tysabri, prompting some individuals to switch to another DMT after achieving disease stability with Tysabri.

Of course, once someone decides to transition away from Tysabri, or any DMT for that matter, the question becomes which therapy to switch to. This retrospective study sought to help answer that question by comparing the experiences of 56 people who moved to fumarate-class DMTs, including Vumerity^® (diroximel fumarate) and Tecfidera^® (dimethyl fumarate), with the experiences of another 56 people who started sphingosine-1-phosphate receptor modulators (S1Ps), such as Gilenya^® (fingolimod), Mayzent^® (siponimod), Ponvory^® (ponesimod), and Zeposia^® (ozanimod).

The two groups were closely matched in terms of demographics and their treatment experience. On average, the study participants waited almost a month (29 days) between stopping Tysabri and starting a new DMT – a period known as a “washout” period.

After one year of treatment on their new DMT, 93.8% of people taking fumarate medications and 87.8% of those taking S1P medications were relapse-free. Meanwhile, the annualized rates of MS-related healthcare visits and healthcare costs were similar for both groups.

Studies such as these provide people with MS and their clinicians with important information to consider when weighing a change in disease-modifying therapy. In the second study, the roughly comparable outcomes seen in people who moved from Tysabri to a fumarate medication or an S1P underscore the welcome breadth of options available to people considering a switch.

 

Enlisting pharmacists in the fight against falls

Can pharmacists help reduce falls in people with MS? Apparently so, according to a small but promising study.¹¹

In September 2023, a health system specialty pharmacist (HSSP) and outpatient neurology clinic in Gulfport, Mississippi, teamed up to implement a fall-prevention program for people with multiple sclerosis. The pharmacist identified patients who had reported a fall in the past 30 days or who had alarming fall signs or symptoms recently documented in their electronic medical record. The pharmacist then offered those people one or more of the following services:

 

• A medication review to identify medications that significantly increase the risk of falling
• Counseling to address personal and environmental risk factors for falling
• Referral to the patient’s provider for an early office visit
• A recommendation to the provider to consider prescribing dalfampridine, a medication that has been shown to improve walking in some people with multiple sclerosis
  

 

An interim analysis of data collected through December 2023 assessed outcomes in 16 people with MS. Those people had a median age of 56.5 years. Sixty-three percent were white and non-Hispanic, and 69% were female. Five reported having fallen at least once in the past 30 days, including three people who said they had fallen two or more times in that period. Eight other patients reported no falls in the prior 30 days, while information on recent falls was not collected for the three remaining patients.

In terms of interventions, 81% had a medication review, while 56% received fall counseling. Twenty-five percent were scheduled for an early visit with their provider, and one patient was prescribed dalfampridine.

And the results? All five patients who had fallen in the 30 days before participating in the program reported a decrease in falls. No patients reported an increase in their number of falls.

The study’s authors concluded, “HSSP pharmacists offer a unique opportunity that may help decrease falls amongst [people with MS]. Having increased touch points with patients and being able to closely collaborate with other healthcare providers enables them to make meaningful interventions and/or recommendations to curtail falls.”

The effort to provide comprehensive care to people with MS is greatly enhanced by assembling a multi-disciplinary care team, including not only physicians, advanced practice providers, and nurses, but often physical and occupational therapists, dietitians, mental health counselors, and other healthcare professionals. This study highlights just one way in which pharmacists can serve as valuable members of that team.

 

“Going the distance” to receive infused MS therapies

Roughly one-quarter of rural residents living in the United States with MS and receive infused disease-modifying therapy (DMT), travel more than 120 miles round-trip for their treatments.¹²

Researchers reported that finding after analyzing data on more than 36,000 Medicare beneficiaries treated with DMTs for multiple sclerosis between January 2017 and December 2022. Seventy percent of the study subjects were female, 83% were white, 70% lived in urban areas, and 72% were receiving Ocrevus^® (ocrelizumab) as their infused DMT.

After excluding people who had a travel distance of more than 250 miles each way on the grounds that those people were outliers, the researchers calculated median travel times for urban residents and for those who lived in large rural areas. (Outliers are amounts that are well beyond the normal range of figures included in a particular calculation and are often left out of the equation… so in this case, people living more than 250 miles each way are “outliers.”)

People living in or near major cities had a median travel time of 54 minutes to their treatment center, while residents of large rural areas had a journey that was almost twice as long, at 103 minutes. And, as referenced above, 22% of those rural residents traveled more than 60 miles each way to receive treatment.

The study’s authors noted, “Among Medicare beneficiaries with MS, travel distance and time for infusion DMTs may pose a significant burden for a substantial number of patients.”

This burden is one of several factors driving researchers to investigate formulations of existing and potential new DMTs that would allow for delivery by subcutaneous injection or other means that don’t require travel to a medical center for administration.

 

References

1. Flechter S, Miller AE, Popper L. Glatiramer acetate depot (extended release) Phase IIa study in patients with primary progressive multiple sclerosis: safety and efficacy snapshot. CMSC 2024 Annual Meeting. Abstract DMT21.
   
2. Rivera Y, Kline A, Montague A. A means to close gaps in multiple sclerosis care. CMSC 2024 Annual Meeting. Abstract QOL20.
   
3. Greene N, Gibbs SN, Broder MS, et al. A longitudinal analysis of multiple sclerosis phenotype transitions using medical charts in the United States. CMSC 2024 Annual Meeting. Abstract NDM04.
   
4. Tomczak AJ, Joseph Y, Sumera J, et al. Bridging the gap between science and practice: the Project BIG Biorepository. CMSC 2024 Annual Meeting. Abstract EP101.
   
5. Amezcua L, Monson NL, Williams MJ et al. One-year analysis of ocrelizumab treatment in Black/African American and Hispanic/Latino people with relapsing multiple sclerosis from the CHIMES trial. CMSC 2024 Annual Meeting. Abstract DMT33.
   
6. Hylton-Gordon R, Peter D, Perunal J. Study of Southeast Asians with MS in comparison to Black and White Americans with MS. CMSC 2024 Annual Meeting. Abstract EPI2.
   
7. Marchese S, Schmidt S, Loud S, Chen A, Singh D. Experiences with switching MS disease-modifying therapies: challenges, facilitators and preferences reported by people with MS. CMSC 2024 Annual Meeting. Abstract LB17.
   
8. Kutz C, Jackson L, Aldridge J, Evans E. Transitioning patients with relapsing multiple sclerosis from anti-CD20 therapies to cladribine tablets in the United States. CMSC 2024 Annual Meeting. Abstract DMT16.
   
9. Kaplan T, Abden Razek MA, Baker AK, et al. Clinical characteristics and treatment outcomes in MS patients treated with natalizumab who switched to moderate-efficacy oral disease-modifying therapies. CMSC 2024 Annual Meeting. Abstract LB10.
   
10. Tysabri^® (natalizumab) injection, for intravenous use [prescribing information]. Biogen Inc. Cambridge, MA. October 2023.
    
11. Fitzpatrick C, Zitterkopf C, Hickman A, Mourani J. Finding balance: a pharmacist-driven fall prevention program for patients with multiple sclerosis. CMSC 2024 Annual Meeting. Abstract MOC02.
    
12. Tai M-H, Palli SR, Shao Q, et al. Travel burden for patients with multiple sclerosis treated with infusion disease modifying therapies. CMSC 2024 Annual Meeting. Abstract DMT37.

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