Low-cost B-cell depleting therapy is as effective as standard treatment for multiple sclerosis

A Norwegian Swedish clinical trial published in the New England Journal of Medicine (NEJM) demonstrates that rituximab, a low-cost B-cell depleting therapy, is as effective as ocrelizumab in newly diagnosed relapsing multiple sclerosis (MS). The study, known as OVERLORD-MS, is the first randomized, double-blind head-to-head trial comparing the two therapies in early MS. Patients from across Norway and Sweden were followed for 30 months with MRI and clinical assessments.

Researchers found comparable efficacy and safety between the treatments.

This study shows that highly effective MS treatment can be delivered at dramatically lower cost without compromising outcomes for patients.”

Øivind Torkildsen, Professor, University of Bergen and consultant neurologist at Haukeland University Hospital

Expanding access to early high-efficacy treatment

Early treatment with highly effective therapies is increasingly recognized as critical for improving long-term outcomes in MS. However, the high cost of many modern MS therapies limits access globally.

The findings from OVERLORD-MS may therefore have major implications not only for healthcare sustainability in high-income countries, but also for treatment access in low- and middle-income regions.

“In many parts of the world, patients still do not have access to modern MS therapies because of cost barriers. Our findings suggest that effective treatment could become available to far more people,” said Torkildsen.

Norway has been among the countries with the most extensive real-world experience using rituximab for MS, and the study provides the first high-level randomized evidence supporting this strategy.

Relevance for EBV-MS research

The OVERLORD-MS trial also contributes important biological material and mechanistic insights to the broader EBV-MS research initiative, an EU-funded collaboration investigating the role of Epstein-Barr virus (EBV) in MS development and progression.

Because rituximab and ocrelizumab work by depleting B cells, the primary reservoir for latent EBV infection, biomaterial collected during the study is now being used to explore how B-cell depletion influences EBV-related immune mechanisms in MS.This creates a unique bridge between clinical treatment research and translational EBV-focused MS research.

Publicly funded academic research with global impact

The study was coordinated by Neuro-SysMed and publicly funded through the Norwegian national clinical trials program KLINBEFORSK.

Researchers highlight the study as an example of how independent academic clinical trials can generate evidence with immediate implications for patients, healthcare systems, and global treatment equity.