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

Abstract

Background: 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.