Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis

Abstract

ImportanceOcrelizumab, a humanized monoclonal antibody targeted against CD20+ B cells, reduces the frequency of relapses by 46% and disability worsening by 40% compared with interferon beta 1a in relapsing-remitting multiple sclerosis (MS). Rituximab, a chimeric monoclonal anti-CD20 agent, is often prescribed as an off-label alternative to ocrelizumab.ObjectiveTo evaluate whether the effectiveness of rituximab is noninferior to ocrelizumab in relapsing-remitting MS.Design, Setting, and ParticipantsThis was an observational cohort study conducted between January 2015 and March 2021. Patients were included in the treatment group for the duration of study therapy and were recruited from the MSBase registry and Danish MS Registry (DMSR). Included patients had a history of relapsing-remitting MS treated with ocrelizumab or rituximab, a minimum 6 months of follow-up, and sufficient data to calculate the propensity score. Patients with comparable baseline characteristics were 1:6 matched with propensity score on age, sex, MS duration, disability (Expanded Disability Status Scale), prior relapse rate, prior therapy, disease activity (relapses, disability accumulation, or both), magnetic resonance imaging lesion burden (missing values imputed), and country.ExposureTreatment with ocrelizumab or rituximab after 2015.Main outcomes and MeasuresNoninferiority comparison of annualized rate of relapses (ARRs), with a prespecified noninferiority margin of 1.63 rate ratio. Secondary end points were relapse and 6-month confirmed disability accumulation in pairwise-censored groups.ResultsOf the 6027 patients with MS who were treated with ocrelizumab or rituximab, a total of 1613 (mean [SD] age; 42.0 [10.8] years; 1089 female [68%]) fulfilled the inclusion criteria and were included in the analysis (898 MSBase, 715 DMSR). A total of 710 patients treated with ocrelizumab (414 MSBase, 296 DMSR) were matched with 186 patients treated with rituximab (110 MSBase, 76 DMSR). Over a pairwise censored mean (SD) follow-up of 1.4 (0.7) years, the ARR ratio was higher in patients treated with rituximab than in those treated with ocrelizumab (rate ratio, 1.8; 95% CI, 1.4-2.4; ARR, 0.20 vs 0.09; P < .001). The cumulative hazard of relapses was higher among patients treated with rituximab than those treated with ocrelizumab (hazard ratio, 2.1; 95% CI, 1.5-3.0). No difference in the risk of disability accumulation was observed between groups. Results were confirmed in sensitivity analyses.ConclusionIn this noninferiority comparative effectiveness observational cohort study, results did not show noninferiority of treatment with rituximab compared with ocrelizumab. As administered in everyday practice, rituximab was associated with a higher risk of relapses than ocrelizumab. The efficacy of rituximab and ocrelizumab administered at uniform doses and intervals is being further evaluated in randomized noninferiority clinical trials.

Potential Medicare and Medicaid Savings on Anti-CD20 Therapy for Multiple Sclerosis

“…Ocrelizumab’s high price relative to rituximab is not justified by comparative effectiveness data. A recent single observational study suggests 1 less relapse per 9 patient-years for those receiving ocrelizumab compared with rituximab, although that study had important limitations . If higher efficacy of ocrelizumab were confirmed in head-to-head randomized trials, its higher price may be partially offset by lower costs from MS complications and justified by better patient outcomes.…”

Evaluating the Therapeutic Potential of Ublituximab in the Treatment of MS: Design, Development and Place in Therapy

“… 23 Although these early-phase trials were positive, further clinical development of rituximab in MS was deferred in favour of ocrelizumab. 60 Despite the lack of Phase III clinical trials of rituximab in MS, rituximab remains used in certain countries as an off-label treatment, although significant variability in dosing regimens exists. Recently, a real-world, retrospective, observational study demonstrated that the efficacy of off-label rituximab is comparable with other highly efficacious DMTs in reducing ARR.…”

Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability

“…There have only been a few studies investigating the relative efficacy of the clinically available anti-CD20 mAbs. A recent observational cohort study evaluated the effectiveness of rituximab versus ocrelizumab in RRMS over a minimum of 6 months using a propensity-matched non-inferiority approach [ 27 ]. A total of 710 ocrelizumab-treated patients were matched to 186 rituximab-treated patients.…”