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CAR-T as a salvage treatment in polyrefractory RA
Merav Lidar1,2, Paula David1, Elad Jacoby2,3,4
1Rheumatology Institute, Sheba Medical Center, Tel Hashomer, Israel.
Rheumatology (Oxford, England)
|June 24, 2026
Summary
Chimeric antigen receptor T cell (CAR-T) therapy targeting CD19 showed significant benefits for patients with severe rheumatoid arthritis (RA) refractory to multiple treatments. This innovative therapy achieved durable remission and improved quality of life, suggesting potential for transformative treatment in advanced RA.
Area of Science:
- Immunology
- Rheumatology
- Cell Therapy
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation.
- Patients with persistent inflammatory refractory RA (PIRRA) often fail multiple lines of therapy, including biologics and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs).
- Novel therapeutic strategies are needed for patients with severe, treatment-resistant RA.
Purpose of the Study:
- To evaluate the efficacy and safety of CD19-directed chimeric antigen receptor T cell (CAR-T) therapy.
- To assess CAR-T therapy in patients with persistent inflammatory refractory rheumatoid arthritis (PIRRA) who have exhausted conventional treatment options.
- To determine the durability of response and long-term safety profile of CAR-T therapy in this patient population.
Main Methods:
- Three women with long-standing, seropositive PIRRA received autologous anti-CD19 CAR-T cell therapy.
- Patients underwent lymphodepletion with fludarabine and cyclophosphamide prior to CAR-T infusion.
- Clinical, laboratory, imaging, and histological outcomes were monitored for up to 18 months post-treatment.
Main Results:
- Two out of three patients achieved drug-free remission within 3 months, with the third patient achieving low disease activity.
- Significant improvements were observed in Health Assessment Questionnaire Disability Index (HAQ-DI) scores, declining rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) titers.
- Histological analysis revealed resolution of synovitis and clearance of CD19+ B cells, indicating histological remission. Acute toxicities like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were manageable, with favorable long-term safety.
Conclusions:
- CD19-directed CAR-T cell therapy demonstrated profound and durable responses in patients with extremely severe seropositive PIRRA.
- Despite significant acute toxicities, recovery was complete, and long-term safety was favorable.
- These findings suggest CAR-T therapy holds transformative potential for severe RA, supporting further investigation in controlled clinical trials.
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