Loading ...

CHARLOTTE, N.C. — Switching from high-efficacy therapies to a fumarate was associated with sustained disease control and a lower rate of infection in patients with multiple sclerosis (MS), results from a small study showed.

Researchers said the findings add to a growing accumulation of data on disease-modifying therapies (DMTs) that supports a strategy that can be used in select patients and is already included in at least one practice guideline.

“While early intervention with a high-efficacy disease-modifying therapy may improve long-term outcomes, transitioning to a moderate-efficacy oral DMT such as dimethyl fumarate may mitigate safety and tolerability concerns after stabilization of disease activity,” reported lead investigator John Scagnelli, MD, a clinical neurologist associated with Raleigh Neurology Associates, Raleigh, North Carolina.

Although the study testing this premise was based on an evaluation of electronic medical records (EHRs) in just 20 patients, previous research has produced similar results, Scagnelli noted.

And the 2025 Update of Best Practices in Multiple Sclerosis Therapies, issued by the Consortium of Multiple Sclerosis Centers, already identifies this de-escalation as a reasonable strategy in older patients with MS. The new findings suggest it may be reasonable in other patients as well.

The new findings were presented on May 28 at the Consortium of Multiple Sclerosis Centers (CMSC) 2026 Annual Meeting.

A Close Look at the Data

For the study, researchers employed data from the NeuroDiscovery AI (NDAI) EHR repository on 20 patients who switched from one of the approved anti-CD20 therapies (ocrelizumab, ofatumumab, or ublituximab) to an approved fumarate (dimethyl fumarate, diroximel fumarate, or monomethyl fumarate).

The primary outcomes evaluated before and after the switch were relapses, disease activity on imaging, and infection events. All were counted as separate events if more than 15 days apart. Relapses were defined as worsening MS symptoms lasting ≥ 24 hours. Activity on imaging involved standard definitions. Infection events required a clinical diagnosis and/or treatment.

On an anti-CD20 therapy, six patients (30%) experienced a relapse during a mean treatment duration of 15.9 months. Following the switch to a fumarate, two patients (10%) had a relapse during a mean duration of 16.1 months.

The proportion of patients with a new T2 lesion was the same during treatment with anti-CD20 therapy and after the switch to a fumarate (15%). However, the only gadolinium-positive lesion reported occurred during anti-CD20 therapy. None of that type were observed after the transition to a fumarate.

The overall annualized infection rate was reduced by about half after the transition from anti-CD20 therapy to a fumarate (1.132 vs 0.0635).

Interestingly, the rate of hospitalizations overall (0.151 vs 0.075) and the number of hospitalizations for SARS-CoV-2 infections specifically (0.075 vs 0.037) were also reduced by about half after patients switched medications.

Among the seven patients for whom lymphocyte data were available, researchers noted a slight increase in mean absolute lymphocyte count after switching to a fumarate.

The most common anti-CD20 therapy was ocrelizumab (75%), while the most common fumarate after the switch was dimethyl fumarate (50%). Most patients cited concerns about infection, lack of efficacy, side effects, and personal preference as reasons for the change in therapy.

The 20 patients in the trial were drawn from 13,150 patients with a history of DMT use in the NDAI database. These represented the only patients in the database who were transitioned directly from an anti-CD20 therapy to a fumarate.

Growing Body of Work

The work adds to a growing body of research suggesting switching medication class is safe and effective, Scagnelli noted.

A small multinational prospective study published in 2024 showed clinical and radiologic stability but an eightfold increase in CD19-positive cells after transitioning from a high-efficacy DMT.

Another report, from a multicenter, retrospective, observational study of 43 patients, showed sustained disease control on the fumarate after transition if patients were well controlled on their previous anti-CD20 therapy.

In addition, a retrospective analysis of a US healthcare claims database comparing 108 switchers to 540 who remained on the anti-CD20 therapy showed that infection rates over 1 year of follow-up were lower in switchers, with no significant differences in relapse rates.

The 2025 CMSC Best Practices Update includes a panel recommendation to consider switching from a high-efficacy therapy to a different DMT class — such as from an anti-CD20 to a fumarate — in older patients with infection, adverse side effects, or personal preference for an oral drug.

In a summary of treating MS in older patients included in the Best Practices Update, Jennifer Graves, MD, PhD, director of Neuro-immunology Research Program at the University of California, San Diego, cited several factors for switching, including the greater risk for infections in older patients losing immunocompetency.

Noting that “DMT efficacy wanes substantially” in older patients she also suggested that the risk to benefit ratio might need to be reevaluated in aging patients, who might be more susceptible to adverse events and other complications related to comorbidities.

Moreover, she suggested a trial transition to a moderately effective oral agent from a high-efficacy agent is not irreversible.

“Patients may be reassured that the decision to discontinue or de-escalate DMTs is an ongoing process and can be changed at any time,” Graves contended in the CMSC document.

More Data Coming

While the new analysis included only 20 patients from the NDAI data repository who switched from an anti-CD20 therapy to a fumarate, Scagnelli told Medscape Medical News that a follow-up analysis has since been conducted. There are now more than 100 in the database, and he thinks this number will continue to grow. He also said other data are coming.

“The safety of the anti-CD20 class of DMTs has become an area of concern,” he said.

Although these are effective therapies, the question has now become “how long do patients need to remain on these drugs before switching to something better tolerated,” Scagnelli added.

Several prospective trials currently underway aim to establish evidence-based strategies for transitioning patients from high-efficacy drugs, he added.

“This has the potential to be a very exciting step forward,” Scagnelli said.

Although his study and several others support the feasibility of transitioning to better tolerated drugs, controlled trials are needed, he added.

“Retrospective data are useful, but they are not the best data to guide practice,” Scagnelli said.

The study received financial support from Biogen. Scagnelli reported having financial relationships with Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Janssen, and Novartis. Graves reported having financial relationships with Atara Biotherapeutics, Biogen, EMD Serono, Novartis, Octave, and TG Therapeutics.