Economic value of anti-CD20 therapies in multiple sclerosis: a systematic review of cost-effectiveness studies

Background: Disease-modifying therapies (DMTs) have transformed multiple sclerosis (MS) care but are associated with substantial costs. Among high-efficacy DMTs, anti-CD20 antibodies are widely used, yet their economic value, particularly compared with different classes of DMTs, has not been comprehensively synthesized. Objective: To systematically review evidence on the cost-effectiveness of anti-CD20 antibodies compared with other DMTs or best supportive care (BSC) in MS. Data sources and methods: We searched PubMed , Embase , Web of Science , and International Network of Agencies for Health Technology Assessment (July 2025) for cost-effectiveness analyses comparing rituximab, ocrelizumab, ofatumumab, or ublituximab with other DMTs or BSC. Two reviewers independently screened studies, extracted data, and assessed reporting quality using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. All costs were converted to 2024 US dollars and adjusted for inflation. Results: Of 92 records screened, 20 studies met inclusion criteria. Analyses were conducted in diverse but mostly high-income regions, most commonly using Markov models with long time horizons. Anti-CD20 antibodies were dominant (more effective, less costly) or cost-effective in the majority of studies, particularly when compared with platform therapies. In contrast, comparisons with other high-efficacy DMTs yielded more heterogeneous results, with immune reconstitution therapies more cost-effective in several studies. Reporting quality was generally high, although patient involvement, assessment of heterogeneity, and a health economic analysis plan were rarely addressed. Conclusion: These findings support the use of anti-CD20 antibodies as an economically reasonable option in many healthcare settings, particularly when compared with platform therapies, while underscoring that cost-effectiveness relative to other high-efficacy treatments is context-dependent. The lack of data from low- and middle-income countries and limited transparency in Health Technology Assessment reports represent major limitations. Future research should prioritize context-specific evaluations and promote full disclosure of economic data to strengthen the evidence base for clinically and economically informed reimbursement decisions in MS. Trial registration: The study was prospectively registered with PROSPERO (ID: CRD420251109958).