At the 2025 European Alliance of Associations for Rheumatology (EULAR) congress in Barcelona, groundbreaking results were presented on the use of CD19-CAR T-cell therapy, a promising new treatment for rheumatologic and musculoskeletal diseases (RMD). This therapy, which involves deep B cell depletion, offers the potential to reset the immune system, possibly leading to durable responses without the need for chronic immunosuppression.
Further data came from the RESET-SSc™ trial, which investigated the use of resecabtagene autoleucel, a fully human 4-1BB anti-CD19-CAR T cell therapy. Dinesh Khanna presented early findings from a three-month follow-up on three patients with severe SSc involving skin or organ damage. The results demonstrated early immunomodulatory-free clinical responses and deep B cell depletion in tissue, as evidenced by lymph node biopsies.
The RESET-Myositis™ trial explored the same therapy in three patients with idiopathic inflammatory myopathy. Raj Tummala reported that the therapy was well tolerated, with no dose-limiting toxicity or severe side effects such as cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). One-month follow-up data showed promising early clinical responses and a favorable safety profile.
In the RESET-SLE™ trial, Saira Sheikh shared data from six patients with non-renal systemic lupus erythematosus (SLE) or lupus nephritis. Over follow-up periods of one to nine months, all patients showed clinical improvement, with several achieving DORIS remission or complete renal response. The treatment was well tolerated, and patients remained free from immunosuppressants.
Rapcabtagene autoleucel, another promising CAR-T therapy, was tested in severe refractory SLE in a Phase 1/2 study. Eric Morand presented data from 21 patients, showing significant disease improvement, effective B cell depletion, and recovery of naive B cell phenotype. The therapy’s safety profile was consistent with previous findings in autoimmune diseases.
Vaneet Sandhu’s team reported on a CAR-T product candidate derived from a clonal master cell bank, engineered from an induced pluripotent stem cell line. This approach allows for off-the-shelf CAR-T cell production, providing broad patient access. Early results from a Phase 1 study in SLE patients showed effective B cell depletion and reconstitution of naive B cells, with promising initial efficacy.
Qiong Fu presented on GC012F (AZD0120), a dual-targeting CD19/B cell maturation antigen (BCMA) CAR-T therapy evaluated in 10 SLE patients. At the nine-month mark, 70% of patients were able to stop glucocorticoids, and 40% also discontinued hydroxychloroquine. The therapy led to normalisation of complement levels and persistent serological conversion in many patients, suggesting its potential for disease remission in refractory SLE.
In the realm of rheumatoid arthritis, Zhu Chen reported results from a small study of three patients with refractory disease. All achieved DAS28-CRP remission within 12 weeks post-infusion, and rheumatoid factor disappeared in all patients. The therapy was well tolerated, with no CRS or ICANS observed, highlighting the potential for CAR-T treatment in difficult-to-treat rheumatoid arthritis.
Ioanna Minopoulou shared findings on CAR-T therapy for ANCA-associated vasculitis, presenting a case study of a 52-year-old patient with severe, treatment-resistant disease. The patient’s symptoms resolved, and granulomas stabilized after CAR-T treatment, without requiring ongoing immunosuppressive therapy.
Finally, Christina Bergmann and colleagues presented data on the effectiveness of CD19-CAR-T therapy in systemic sclerosis (SSc). Their study demonstrated improvements in disease activity scores, with patients showing significant clinical responses. Median times to achieve inactive disease and good response were 211 days and 80.5 days, respectively.
These presentations underscore the potential of CAR-T cell therapy and other B cell-depleting treatments to reset the immune system in multiple RMDs, offering patients lasting clinical benefits without the need for continuous immunosuppressive therapy.
Related Topics:
