Low-cost MS treatment shown to be as effective as standard therapy in landmark trial

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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.

The study, known as OVERLORD-MS, is the first randomized, double-blind head-to-head trial comparing the two therapies in early multiple sclerosis. 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 multiple sclerosis treatment can be delivered at dramatically lower cost without compromising outcomes for patients,” said Øivind Torkildsen, Professor at the 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 multiple sclerosis. However, the high cost of many modern multiple sclerosis 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 multiple sclerosis 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 multiple sclerosis, 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 in multiple sclerosis development and progression.

Because rituximab and ocrelizumab work by depleting B cells, the primary reservoir for latent Epstein–Barr virus infection, biomaterial collected during the study is now being used to explore how B-cell depletion influences Epstein–Barr virus-related immune mechanisms in multiple sclerosis.

This creates a unique bridge between clinical treatment research and translational Epstein–Barr virus-focused multiple sclerosis 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.

About the study

• Published in the New England Journal of Medicine
• Randomized, double-blind multicenter trial
• Compared rituximab and ocrelizumab in newly diagnosed relapsing multiple sclerosis
• 30 months follow-up
• Conducted across Norway and Sweden
• Publicly funded through KLINBEFORSK

Source: News Release
The University of Bergen
July 2, 2026