A new therapeutic frontier: CD19-targeting CAR-T cell therapy in rheumatoid arthritis: a concise report

OBJECTIVES: Chimeric antigen receptor (CAR)-T cell therapy recently emerged as a possible new treatment option in refractory systemic autoimmune diseases (AID). With growing evidence in B cell-mediated AID, the question arises as to its potential application in difficult to treat RA. Building on positive experience in a case of overlapping seropositive RA and SSc treated with CD19 CAR-T cells at our centre, we reviewed the available evidence on the efficacy and safety of CAR-T cell therapy in RA. METHODS: The patient successfully received a single infusion of autologous CD19 CAR-T cells (KYV-101, Kyverna Therapeutics) after lymphodepletion with fludarabine and CYC. Clinical, serologic and safety outcomes were monitored over 12 months, demonstrating sustained disease remission and improvement in interstitial lung disease. Furthermore, a literature review analysed prior cases of CAR-T cell treatment in RA, focusing on patient characteristics, outcomes and adverse events. RESULTS: Seven of eight previously published cases of CAR-T cell therapy in RA (7/8 ACPA positive) consistently reported significant improvement, with most patients remained stable off immunosuppressive therapy after a median follow-up of 9 months. High-grade cytokine release syndrome (grade 3) and immune cell-associated neurotoxicity syndrome (grade 4) was reported only in one patient. No serious infections were observed, even though transient hypogammoglobulinaemia occurred in two patients (2/8). CONCLUSION: The eight reported cases highlight the potential of CAR-T cell therapy, even in patients unresponsive to B cell-targeted treatments in RA. Larger and prospective studies are needed to assess its long-term efficacy and safety in the disease.