A Norwegian-Swedish clinical trial published in the New England Journal of Medicine (NEJM) demonstrated that rituximab, a low-cost B-cell depletion therapy, is as effective as ocrelizumab for newly diagnosed relapsing multiple sclerosis (MS). The study, known as OVERLORD-MS, is the first randomized, double-blind, head-to-head trial comparing two treatments in early MS. Patients from all over Norway and Sweden were followed for 30 months with MRI and clinical evaluation.
Researchers found comparable efficacy and safety with each treatment.
This study shows that highly effective MS treatments can be delivered at dramatically lower cost without compromising patient outcomes. ”
Øyvind Torkildsen, Professor at the University of Bergen and Consultant Neurologist at Haukeland University Hospital
Expanding access to early and effective treatments
Early treatment with highly effective therapies is increasingly recognized as critical to improving long-term outcomes in MS. However, the high cost of many modern MS treatments limits access worldwide.
Therefore, the OVERLORD-MS findings could have a major impact not only on health care sustainability in high-income countries, but also on treatment access in low- and middle-income regions.
“In many parts of the world, cost barriers still prevent patients from accessing the latest treatments for multiple sclerosis. Our findings suggest that more people may have access to effective treatments,” Thorkildsen said.
Norway is one of the countries with the most experience using rituximab for MS, and this study provides the first high-level randomized evidence to support this strategy.
Relevance to EBV-MS research
The OVERLORD-MS trial will also provide important biological and mechanistic insights for the broader EBV-MS research initiative, a collaborative EU-funded study investigating the role of Epstein-Barr virus (EBV) in the development and progression of MS.
Because rituximab and ocrelizumab act by depleting B cells, which are the main reservoir of latent EBV infection, biomaterials collected during the study are currently being used to examine how B cell depletion affects EBV-related immune mechanisms in MS. This creates a unique bridge between clinical treatment research and MS research focused on translational EBV.
Publicly funded academic research that impacts the world
The study was coordinated by Neuro-SysMed and publicly funded through the Norwegian national clinical trials program KLINBEFORSK.
Researchers highlight this study as an example of how independent academic clinical trials can generate evidence that has an immediate impact on patients, health systems, and global treatment equity.
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Reference magazines:
Thorkildsen, Ø, Others. (2026) Rituximab and ocrelizumab in newly diagnosed relapsing multiple sclerosis. New England Medical Journal. DOI: 10.1056/NEJMoa2600993. https://www.nejm.org/doi/full/10.1056/NEJMoa2600993
