Halving the yearly rituximab dose maintains efficacy in RRMS

In a Swedish multicentre study, rituximab 500 mg given once yearly was non-inferior to 500 mg every 6 months as maintenance therapy for eliminating inflammatory activity in relapsing-remitting MS (RRMS). Over the course of 3 years, no evidence of disease activity (NEDA-3) was maintained in approximately 87% of patients in both arms.

B cells have long been implicated in MS. Anti-CD20 therapies such as ocrelizumab and ofatumumab are approved for MS. Still, rituximab—the original anti-CD20 antibody—has been widely used off-label, particularly in Sweden, where “we do things differently”, noted Prof. Anders Svenningsson (Karolinska Institute, Sweden). Results from the phase 3 trial RIFUND-MS, conducted by Prof. Svenningsson and colleagues, contributed to the licensing of rituximab for MS [1].

Concerns about infections prompted the RIDOSE study (NCT03979456), which evaluated the non-inferiority of an extended 12-month dosing regimen compared with standard 6-month rituximab dosing [2]. RIDOSE was a rater-blinded Swedish trial in which participants were randomised 1:1 to rituximab 500 mg every 6 months (standard dosing; n=103) or 500 mg every 12 months (extended dosing; n=103) for 3 years, after an initial year of  6-monthly dosing. The primary endpoint was non-inferiority of the extended dosing regimen in maintaining NEDA-3 during years 2-4.

Participants had RRMS or a clinically isolated syndrome (CIS). The mean age was 36 years. In years 2-4, extended and standard dosing were equally effective in maintaining NEDA-3. The percentage of participants not maintaining NEDA-3 was 13.59% and 12.62%, respectively (HR 0.93; 95% CI 0.44-1.98; log-rank P-value=0.853). Across 4 years, there were 5 and 7 relapses in the extended and standard dosing groups, respectively (P=0.5). A total of 36 new lesions appeared in 12 participants and 10 participants, respectively (P=0.7).

Adverse events were equally distributed between groups. Most infections were related to COVID-19. Severe infections occurred in 11 participants in the extended and 8 in the standard group. Declines in immunoglobulin levels were less pronounced with extended dosing, suggesting potential long-term safety benefits.

Prof. Svenningsson concluded that IV anti-CD20 therapies are generally dosed too high, which may expose patients to unnecessary safety risks. The risk-benefit profile of individualised dosing schedules is likely superior to fixed dosing.

1. Svenningsson A, et al. Lancet Neurol. 2022;21(8):693-703.
2. Svenningsson A, et al. Rituximab long-term DOSE trial in Multiple Sclerosis – RIDOSE-MS. A phase 3 trial investigating extended dosing regimen of rituximab in relapsing-remitting MS. O131, ECTRIMS 2025 Congress, 24-26 September 2025, Barcelona, Spain.

Medical writing support was provided by Michiel Tent.

Copyright ©2025 Medicom Medical Publishers

 



Posted on 30 September 202530 September 2025