Cost Effectiveness of Rituximab Therapy for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Cost-Utility Studies

Background and Objectives: Depletion of B cells is shown to be clinically effective for rheumatoid arthritis (RA) treatment. Although B-cell depletion therapy with rituximab is indicated for RA patients who have failed to other disease-modifying anti-rheumatic drugs (DMARDs), primary cost-effectiveness evidence is inconsistent. We aimed to provide synthesised cost-effectiveness evidence of rituximab in the treatment of RA compared to other DMARDs, since the published cost-effectiveness evidence is mixed. Methods: We identified economic evaluation studies reporting cost-utility of rituximab compared to other DMARDs by searching PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry. Using random-effects meta-analysis, we pooled incremental net benefit (INB) in (purchasing power parity) adjusted US$ with 95% confidence intervals. We used the modified economic evaluations bias checklist and Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) instrument for quality appraisal. The study protocol was pre-registered with PROSPERO, CRD 42021222541. Results: Of the selected 18 studies, the majority were from high-income countries (n = 14) followed by upper middle-income countries (n = 3) and lower middle-income countries (n = 1), with minimal risk of bias. Rituximab is significantly cost effective with a pooled INB (95% CI) of $8767 (720 to 16,814). On subgroup analysis, rituximab is significantly cost effective from a health system perspective [$12,832 (3392 to 22,272)], for studies using 3.5% discount rate [$15,468 (5973 to 24,963)] and a for a time horizon of less than 5 years [$8496 (1547 to 15,445)]. In a separate analysis, rituximab as third-line therapy (for conventional synthetic DMARDs followed by any other biologic DMARD failed patients) was not cost effective compared to DMARDs [$5314 (−2278 to 12,905)]. Further, the GRADE assessment indicated very-low confidence in the pooled results. Conclusion: Rituximab is cost effective compared to other DMARDs but not if used as third-line therapy after failure of biologics. There is a need to generate context-specific evidence for the lower income settings.