Innovative therapies in rheumatoid arthritis: CAR T cells and bispecific antibodies.

Rheumatoid arthritis is a chronic immune-mediated inflammatory disease, and therapeutic strategies predominantly rely on continuous immunomodulation. Despite major advances with biological and targeted synthetic disease-modifying antirheumatic drugs, some patients develop persistent, objectively active inflammatory disease that remains refractory to multiple therapeutic mechanisms. Durable drug-free remission is rare, highlighting a major unmet need. Emerging deep B-cell depleting therapies, including bispecific T-cell engagers and chimeric antigen receptor (CAR) T-cell-based therapies, challenge the current treatment framework by aiming to eradicate or reprogramme pathogenic immune memory rather than chronically suppress inflammatory pathways. Early clinical evidence in rheumatoid arthritis suggests that CD19-directed T-cell engagers and B-cell depleting CAR T cells might induce profound immunological remodelling and sustained drug-free remission in some individuals. This Review critically appraises the available clinical and translational evidence supporting deep B-cell depleting therapies in rheumatoid arthritis, compares their mechanisms, feasibility, and harms, and discusses their potential positioning across the disease spectrum. Finally, this Review proposes a research agenda that prioritises innovative trial designs, deep immunomonitoring, tissue-based analyses, and long-term safety surveillance to responsibly translate deep B-cell depleting strategies into rheumatology practice.