Anti-CD20 antibodies in relapsing multiple sclerosis: Protocol for a systematic review and network meta-analysis

BackgroundMultiple sclerosis is a chronic disease of the central nervous system characterized by autoimmune demyelination. Various immunomodulatory medications are available for its treatment, among which anti-CD20 monoclonal antibodies have demonstrated superior efficacy compared to other disease-modifying therapies. However, there is a lack of direct comparison between the four available anti-CD20 monoclonal antibodies. Therefore, this study aims to systematically assess the relative efficacy and safety of anti-CD20 monoclonal antibodies for treating relapsing multiple sclerosis. Materials and MethodsWe will conduct a systematic review of phase IIb and phase III clinical trials of anti-CD20 monoclonal antibodies for the treatment of relapsing multiple sclerosis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A comprehensive review of the Cochrane Central Register of Controlled Trials; MEDLINE; Embase; ClinicalTrials; International Clinical Trials Registry Platform; OpenGray; and MedRxiv will be performed. Two independent reviewers will select titles, abstracts, and eligible full texts to execute the data extraction. The risk of bias will be assessed with the Cochrane RoB 2 tool. Data on pre-specified outcomes will be analyzed for the selected articles using a random-effects network meta-analysis with a frequentist framework. Summary statistics, along with 95% confidence intervals will be presented, and the effectiveness and safety of each intervention will be ranked using the surface under the cumulative ranking curve. A missing data and a sensitivity analysis will be conducted. We will use the GRADE approach to assess the certainty of the direct, indirect, and network estimate for all outcomes. Results and ConclusionThe results will provide evidence of the relative efficacy and safety of anti-CD20 monoclonal antibodies for the treatment of relapsing multiple sclerosis. Systematic review registrationPROSPERO registration number CRD42023437996