Evolving role of Anti-CD20 monoclonal antibodies in rheumatoid arthritis: efficacy, safety, economic perspectives, and future directions-a narrative review.

backgroundB-cell depletion has established an important therapeutic role in rheumatoid arthritis (RA), particularly in selected patients with an inadequate response to tumor necrosis factor inhibitors or with clinical features favoring rituximab. However, the optimal positioning of anti-CD20 therapy remains constrained by heterogeneous treatment responses, cumulative immunosuppression, retreatment strategies, and differences in treatment accessibility. MAIN TEXT: This narrative review synthesizes evidence from randomized controlled trials, long-term extension studies, real-world cohorts, mechanistic investigations, biosimilar studies, and pharmacoeconomic evaluations. Rituximab remains the only anti-CD20 monoclonal antibody with an established clinical role in RA. Newer-generation agents, including ocrelizumab, ofatumumab, and obinutuzumab, incorporate humanized, fully human, or glycoengineered designs that modify antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, direct cell death, and immunogenicity. Nevertheless, greater B-cell-depleting potency has not consistently translated into an acceptable long-term benefit-risk profile in RA. This discrepancy is described here as a "next-generation paradox," reflecting the narrower safety margin required in chronic autoimmune disease than in hematological malignancies. Rituximab biosimilars may improve treatment accessibility, although their economic impact is strongly dependent on regional procurement and reimbursement systems. Biomarker-guided patient selection, ultra-low-dose maintenance regimens, and dual targeting of B cells and BAFF axis represent promising approaches to treatment optimization., but their routine use remains limited by heterogeneous and, in some cases, non-RA-specific evidence.

conclusionsRituximab retains clinically relevant value in carefully selected patients with RA, particularly seropositive patients and those for whom alternative targeted therapies are unsuitable. Future research should prioritize RA-specific prospective validation of biomarkers, individualized retreatment strategies, long-term immune safety, and regionally relevant pharmacoeconomic models rather than simply pursuing more potent B-cell depletion.