Rituximab in secondary progressive multiple sclerosis: a meta-analysis

Objective

To evaluate the efficacy of rituximab (RTX) in stabilizing disability progression in secondary progressive multiple sclerosis (SPMS).

Methods

A systematic review was conducted, encompassing studies from inception to April 2023, utilizing the MEDLINE and EMBASE databases. Inclusion criteria comprised studies with a minimum of 3 SPMS patients receiving intravenous RTX in at least one infusion, with a follow-up duration of at least 6 months. Primary outcome measures included changes in Expanded Disability Status Scale (EDSS) scores. Mean differences in pre- and post-RTX EDSS scores were analyzed using a random-effects model. Meta-regression examined age at RTX initiation, pre-RTX EDSS scores, disease duration, and outcome reported time as variables. Secondary outcomes assessed changes in the annualized relapse rate (ARR).

Results

Thirteen studies, involving 604 SPMS patients, met the inclusion criteria. Following a mean follow-up of 2 years, the mean difference in EDSS scores (ΔEDSS = EDSS_pre-RTX − EDSS_post-RTX) was −0.21 (95% CI −0.51 to 0.08, p = 0.16), indicating no significant variation. Multivariable meta-regression identified significant associations between EDSS score mean difference and pre-RTX EDSS scores, disease duration at RTX initiation, and outcome reported time. However, age at RTX initiation showed no significant association. Pre- and post-RTX ARR data were available for 245 out of 604 SPMS patients across seven studies, revealing a mean difference in ARR (ΔARR = ARR_pre-RTX − ARR_post-RTX) of 0.74 (95% CI 0.19–1.29, p = 0.008).

Interpretation

RTX demonstrates efficacy in reducing relapse frequency and exhibits potential in stabilizing disability progression over a 2-year follow-up, particularly among individuals with shorter disease duration.