Restricted accessResearch articleFirst published online 2026-4
De-escalating low-dose rituximab up to every 24-month infusions and the risk of disease activity in people with relapsing multiple sclerosis who were stable the first year on therapy
Higher cumulative rituximab doses are associated with greater risks of infections. Therefore, we routinely extend low-dose rituximab (500 mg) intervals in people with relapsing multiple sclerosis (pwRMS) from every 6(q6mo) to 12 months(q12mo) to 18(q18mo) and/or 24 months(q24mo).
Objective:
To determine whether q18–24mo extension increases disease activity risks compared to continuing q6–12mo intervals.
Methods:
We conducted a retrospective cohort study of rituximab-treated pwRMS with no evidence of disease activity (absence of relapses, MRI disease activity and disability progression, NEDA-3, 96.6%) during the first year on rituximab.
Results:
We identified 1052 patients (mean age = 38.5 years; 71.5% female). 467 (44.4%) pwRMS received at least one q18–24mo 500 mg interval and 585 never extended beyond q6–12mo. Relapses and/or MRI disease activity (2.4%) and failing NEDA-3 (2.9%) were uncommon. Extending dosing to q18–24mo was not associated with an increased risk of failing NEDA-3 in inverse probability of treatment weighting propensity-score adjusted intention-to-treat (hazard ratio [HR] = 0.57, 95%CI = 0.21–1.57, p = 0.275) or per-protocol analyses (HR = 0.56, 95%CI = 0.17–1.86, p = 0.348) over 3–5 years of follow-up.
Conclusion:
Extending low-dose rituximab after at least 1 year of clinical and radiological stability up to q24mo was not associated with an increased risk of disease activity compared to continuing q6–12mo intervals in this large, population-based cohort.
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