CAR-T as a salvage treatment in polyrefractory rheumatoid arthritis
Merav Lidar, Paula David, Elad Jacoby, Ronnie Shapira-Frommer, Orit Itzhaki, Yael Eshet, Iris Eshed, Ronit Marcus, Avichai Shimoni, Ronit Yerushalmi, Ivetta Danylesko, Noga Shem Tov, Gleb Slobodin, Lisa Kaly, Reem Samara, Abraham Avigdor, Doron RimarAbstract
Objectives
To evaluate the utility of CD19-directed chimeric antigen receptor T cell (CAR-T) therapy in patients with persistent inflammatory refractory rheumatoid arthritis (PIRRA), who failed ≥5 biologic/targeted synthetic disease-modifying anti-rheumatic drugs (DMARD) classes.
Methods
Three women with long-standing, seropositive PIRRA received autologous anti-CD19 CAR-T therapy with CD 28 co-stimulation. After lymphodepletion with fludarabine and cyclophosphamide, an infusion of 0.6–1 × 106 CAR-T cells/kg was administered. Clinical, laboratory, imaging and histological outcomes were assessed up to 18 months.
Results
Median age was 54 years (range 39–68), and median disease duration was 14 ± 3.1 years. All developed grade 3 cytokine release syndrome (CRS), and one developed grade 4 ICANS. No long-term toxicities were observed, except for hypogammaglobulinemia, that has not required replacement therapy. Within 3 months, two patients achieved remission, and onehad low disease activity. At the last follow-up, two remained in drug-free remission, and one attained low disease activity with abatacept and methotrexate. HAQ-DI scores improved from severe disability to near-normal. RF and ACPA titers markedly declined. Furthermore, imaging demonstrated resolution of synovitis and clearance of CD19+B cells from the synovium establishing histological remission.
Conclusion
CD19 CAR-T therapy induced profound, durable responses in extremely severe patients with seropositive PIRRA. Despite significant acute toxicities, recovery was complete, and long-term safety was favorable. These findings suggest that CAR-T may provide a transformative benefit in severe RA, warranting controlled clinical trials.