For people living with multiple sclerosis (MS), the choice of treatment can affect their mobility, work, and everyday independence. MS occurs when the immune system damages the protective covering around nerves in the brain and spinal cord. In its relapsing-remitting form, it causes attacks of new or worsening symptoms, followed by periods of partial or complete recovery. Understanding how treatments perform in routine care, including their benefits and drawbacks, can help patients and clinicians choose the medication that best serves their needs and priorities.

Dr. Maya Zeineddine, clinical associate professor and chair of the Department of Pharmacy Practice, and Dr. Hani Dimassi, professor and chair of the Department of Pharmaceutical Sciences, both at the School of Pharmacy, co-authored a study titled “Comparative effectiveness of natalizumab and anti-CD20 monoclonal antibodies in relapsing-remitting multiple sclerosis: a real-world propensity-score matched study” and published in the Journal of Neurology, Neurosurgery and Psychiatry. The study compares the effectiveness and safety of two common sclerosis treatments, natalizumab and the anti-CD20 treatment group, to better guide patients and clinicians.

The two treatments work differently on the immune system. Natalizumab limits immune cells from entering the brain and spinal cord, while anti-CD20 therapies such as rituximab and ocrelizumab target and reduce specific immune cells called B cells that contribute to MS.

“Both natalizumab and anti-CD20 antibodies are highly effective therapies, so the choice is usually individualized rather than based on efficacy alone,” explained Dr. Zeineddine, adding that clinicians consider disease activity, previous treatments and the risks associated with each option, alongside pregnancy plans, other health conditions and patient preferences. Practical factors, including treatment schedules, how the medication is given, access and cost, also influence the decision.

From about 15,000 patient records across seven countries in the Middle East and North Africa, the researchers identified 1,954 eligible adults receiving natalizumab, rituximab or ocrelizumab, lab-made antibodies that act on selected targets in the immune system. For a balanced comparison, the researchers selected people with similar starting characteristics, creating groups of 677 natalizumab users and 587 users of the other two medicines.

Patients taking natalizumab had the fewest relapses, averaging 6.2 per 100 people each year, compared to 9.2 for those on the other medications. Among patients with enough records to assess changes in disability, 9.3 percent of natalizumab users and 5.5 percent of the comparison group had a long-term reduction in the degree of disability, as measured on a clinical disability scale. Rates of disability progression and measures of disease activity on MRI, however, were similar between the groups.

The findings also show that fewer reported adverse effects do not necessarily mean patients stay on a medicine longer. Natalizumab users, who experienced fewer health problems than the comparison group, were more likely to stop their medication, mainly because of insufficient disease control and concerns about a rare but serious brain infection associated with natalizumab.

“Our findings, therefore, do not suggest that one therapy is universally preferable,” said Dr. Zeineddine. Natalizumab may be particularly attractive when rapid disease control is a priority or when doctors want to avoid suppressing the immune system, she explained. Anti-CD20 therapy, meanwhile, may be favored when concerns about PML, the rare brain infection associated with natalizumab, or the likelihood of staying longer on the treatment carry greater weight.

“The principal limitation stems from the observational nature of the study,” noted Dr. Dimassi. Matching patients with similar recorded characteristics helps balance the treatment groups, but factors that were not measured or were incompletely documented may still affect the comparison, he added.

Dr. Dimassi added that more complete and standardized registry data are a priority for future work, particularly records of when treatments start and stop, relapses, MRI scans, disability assessments, dosing intervals and adverse events. Future analyses should also examine rituximab and ocrelizumab separately and account for differences in doses and the intervals between them, said Dr. Zeineddine. Following patients prospectively, with assessments scheduled in advance and consistent data collection, would help address several of these limitations, she added.

“Ultimately, however, a randomized head-to-head trial would provide the most robust evidence, although conducting such a trial may be challenging,” concluded Dr. Dimassi.

The study offers evidence to support clinicians and patients alike. The results can help people weigh attack control, lasting physical improvement, treatment risks, and continuity of care, while leaving room for choices shaped by their own lifestyle circumstances.

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