To assess the efficacy of alternative dosing strategies (ADS), including extended-interval dosing (EID) and dose reduction, compared with standard dosing strategies (SDS) of anti-CD20 monoclonal antibodies in multiple sclerosis (MS).

Anti-CD20 monoclonal antibodies(ocrelizumab, rituximab, ofatumumab) are effective in controlling MS activity. While SDS are established, concerns about infection risk, safety, and cost have led to growing interest in ADS. The comparative efficacy of these approaches remains unclear.

PubMed, Embase and Cochrane databases were systematically searched from inception to July 2025 for clinical studies comparing ADS with SDS of anti-CD20 monoclonal antibodies in MS. Outcomes included relapse rates, MRI activity, disability progression, and NEDA-3(No Evidence of Disease Activity)status. Two reviewers independently extracted study and patient data. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models in Review Manager5.4. Subgroup analyses were performed for EID and dose reduction.

From 1785 records screened, 22 studies published between 2018 and 2025 were eligible for inclusion. These comprised 14 on ocrelizumab, 6 on rituximab, one mixed and one on ofatumumab. The majority (n = 18) assessed EID, while four evaluated reduced-dose regimens. Pooled analysis showed that EID showed no significant difference compared to standard dosing with respect to relapse risk(RR 0.7, 95% CI 0.47-1.04), MRI activity(RR 0.93, 95% CI 0.68-1.26), disability progression(RR 0.96, 95% CI 0.45-2.08), and achievement of NEDA-3(RR 1.06, 95% CI 0.6–1.9). The four dose-reduction studies also demonstrated no loss of efficacy across clinical and radiological outcomes.

Alternative dosing strategies of anti-CD20 monoclonal antibodies appear to provide disease control comparable to standard regimens. Extended interval dosing didnot increase the risk of relapse, MRI activity, disability progression, or NEDA-3 loss. Dose reduction showed similarly stable outcomes, though current evidence remains limited. Larger prospective trials are warranted to confirm the safety and durability of these approaches before routine adoption.