Yearly Rituximab Dosing Shows Comparable Efficacy to Standard 6-Month Regimen in Relapsing-Remitting MS

New late breaking data presented at the 2025 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 24-26, in Barcelona, Spain, from the phase 3 RIDOSE-MS trial (NCT03979456) revealed that annual dosing of 500-mg rituximab was as effective as the conventional 6-monthly treatment regimen for controlling disease activity in patients with relapsing-remitting multiple sclerosis (RRMS).¹

RIDOSE-MS enrolled 207 participants with RRMS, randomizing 104 patients to the 12-month dosing arm and 103 participants to the 6-month arm. During the 4-year follow-up, investigators recorded 12 protocol-defined relapses across both groups, corresponding to an annual relapse rate of 0.015. Researchers reported that 7 relapses occurred in the 6-month arm and 5 occurred in the 12-month arm (P = 0.5). Across the entire trial period, 36 new lesions were detected in 22 unique participants, 12 observed in the annual dosing group and 10 reported in the 6-month group (P = 0.7).

The randomized, rater-blinded trial compared 500-mg rituximab administered every 12 months with the same dose given every 6 months, following an initial year of standard 6-monthly dosing. Over the 3-year randomized period, annual dosing achieved the primary outcome of noninferiority on the composite measure of no evidence of disease activity, which tracks relapses, new or enlarging T2 MRI lesions, and confirmed disability progression. Secondary analyses included biomarker changes and safety assessments, with particular attention to reductions in immunoglobulin G (IgG) levels and the development of hypogammaglobulinemia.

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Presented by lead author Anders Svenningsson, MD, PhD, professor of neurology in the Department of Clinical Sciences at Karolinska Institutet Danderyd Hospital in Stockholm, Sweden, the current study builds on prior evidence from the RIFUND-MS trial (NCT02746744), which demonstrated rituximab’s superiority over dimethyl fumarate in reducing relapses and MRI activity in RRMS. Notably, the annual relapse rate observed in the RIDOSE-MS trial was consistent with that seen in the rituximab arm of RIFUND-MS study.²

All told, safety outcomes in the trial were comparable between the 2 treatment schedules in patients with RRMS. Adverse events (AEs) were evenly distributed, with no new safety signals identified among participants. Importantly, the rate of IgG reduction, a marker of immune suppression, was approximately 25% slower in patients who received rituximab once yearly compared with those on the semiannual schedule. Despite not observing any signal of less infections in the extended dose arm, researchers suggested that the lower decline in immunoglobulin levels could lead to long-term safety advantages from a lower accumulated dose over time.

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REFERENCES
1. Svenningsson A, Frisell T, Burman J, 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. Presented at ECTRIMS Congress; September 24-26, 2025; Barcelona, Spain. Late-Breaking Abstract O131.
2. Svenningsson A, Frisell T, Burman J, et al. Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial. Lancet Neurol. 2022;21(8):693-703. doi:10.1016/S1474-4422(22)00209-5