CAR-T as a salvage treatment in polyrefractory rheumatoid arthritis
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ID: 318514
2026
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Abstract
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.
| Reference Key |
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| Authors | 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, A AvigDor, Doron Rimar |
| Journal | Lara D. Veeken |
| Year | 2026 |
| DOI |
10.1093/rheumatology/keag273
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| URL | |
| Keywords | Keywords not found |
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