Disease: Multiple Sclerosis
Type of study: Interventional trial
Coordinating investigator: Øivind Torkildsen
Study director: Kjell-Morten Myhr
Background: B-cell depletion therapy is highly effective in relapsing-remitting MS. Rituximab seems to have a comparable efficacy and safety profile to ocrelizumab, but data on optimal dosing are limited and largely based on various off-label regimes. The most frequently used dosing regimen in Norway (until recently) has been a single starting dose of 1000 mg infusion, followed by 500 mg infusions every six months for an undefined time. The therapy seems safe, and limited side effects are reported, where neutropenia, lymphopenia, hypogammaglobulinemia, and infections are the most frequent adverse events.
Real-world experience indicates that B-cells may be depleted for a longer period, even for at least 12–24 months, and longer dosing intervals than six months (e.g., due to intercurrent illness or pregnancy planning) seem safe. Based on these observations, clinical practice in Norway is changing to extended dosing intervals after at least two years of therapy. In this study, we aim to investigate the efficacy and safety of extending the dosing interval to 12 or 24 months in RRMS.
All patients finishing the OVERLORD-MS study who have been stable without new MRI or clinical disease activity for at least two years will be offered an extension of further rituximab (500 mg) dosing interval to 12 or 24 months.
The objectives of the study are to evaluate whether the efficacy and safety of 24-month dosing of rituximab is equal in efficacy and with a lower risk of side effects than 12-month dosing.
Design: This is a randomized, double-blind, non-inferiority study comparing the efficacy and safety of 12 versus 24 months of rituximab in relapsing-remitting MS patients.
The primary endpoint of the study is the proportion of patients with no new or expanding T2-lesions.
Status: The study is expected to start recruiting patients in Q2 2026 and will prospectively recruit patients who have finished the OVERLORD-MS study period, including the following switch period of 6 months.
Participating centres
Norway
- Haukeland University Hospital, Bergen
- Oslo University Hospital, Oslo
- Akershus University Hospital, Lørenskog
- Stavanger University Hospital, Stavanger
- University Hospital of North Norway, Tromsø
- Nordland Hospital Trust, Bodø
- Namsos Hospital Trust, Namsos
- Molde Hospital Trust, Molde
- Sørlandet Hospital Trust, Kristiansand
- Telemark Hospital Trust, Skien
- Vestre Viken Hospital Trust, Drammen
Sweden
- Karolinska Institute, Stockholm
Funding
- The Research Council of Norway, Neuro-SysMed
- The Regional Health Authority of Western Norway
- Haukeland University Hospital
- The University of Bergen
- The DAM foundation
- Participating hospitals