Study fails to show non-inferiority of rituximab with ocrelizumab

A non-inferiority comparative study failed to demonstrate that treatment with rituximab is non-inferior to ocrelizumab in relapsing-remitting MS (RRMS). Rituximab was associated with a higher relapse risk than ocrelizumab.

B-cell therapies are highly effective treatments for RRMS. Ocrelizumab is a humanised, monoclonal antibody targeted against CD20+ B cells, which reduces the frequency of relapses by 46% and disability worsening by 40% compared with interferon-β 1a. Rituximab is a chimeric, monoclonal, anti-CD20 agent that serves as an off-label alternative to ocrelizumab.

A study evaluated the clinical non-inferiority of rituximab with ocrelizumab in RRMS. It was designed as a longitudinal, observational, cohort study that used 2 large MS registries: MSBase and the Danish MS registry (DMSR). Patients had to be pre-treated with either rituximab or ocrelizumab for at least 6 months. Patients with comparable baseline characteristics were matched 1-to-6 by propensity score on age, sex, MS duration, Expanded Disability Status Scale (EDSS), prior relapse rate, prior therapy, disease activity, MRI lesion burden, and country. The primary study outcome measure was the annualised-relapse rate (ARR). The pre-specified, non-inferiority margin was 1.2 rate ratio. Secondary outcome measures were the cumulative hazard of relapse, 6-months confirmed disability accumulation, and 6-months confirmed disability improvement. Dr Izanne Roos (University of Melbourne, Australia) presented the results.

Included were 1,613 patients; 898 from MSBase and 715 from the Danish registry. Of these, 1,354 received treatment with ocrelizumab and 259 with rituximab. Over a mean follow-up of 1.5 years, the ARR ratio was higher in rituximab-treated patients, with a rate ratio of 1.8 (95% CI 1.4–2.4). ARR was 0.20 for rituximab versus 0.09 for ocrelizumab (P<0.01). The cumulative hazard of relapse was higher in the rituximab group (HR 2.8; 95% CI 1.46–2.96; P<0.001) but the cumulative hazard of disability accumulation was not different (HR 1.51; 95% CI 0.86–2.64; P<0.15). Follow-up was insufficient to draw definitive conclusions on disability outcomes. Results were confirmed in sensitivity analyses with an intention-to-treat design.

The comparative effectiveness of rituximab and ocrelizumab should be further evaluated in randomised, clinical, non-inferiority trials.

1. Roos I, et al. A non-inferiority study of rituximab versus ocrelizumab in relapsing-remitting multiple sclerosis. Abstract O180, ECTRIMS 2022, 26–28 October, Amsterdam, Netherlands.

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Posted on 31 October 2022