A clinical trial at Charité-Universitätsmedizin Berlin used CD19 CAR T-cell therapy to put six patients with severe rheumatoid arthritis into remission, marking the first study of its kind. Disease activity dropped markedly in all participants, with three achieving sustained remission without medication, according to research published in Nature Medicine.
Immunotherapies like CAR T-cell therapy, originally developed for cancer, are now being tested as treatments for autoimmune diseases. In a groundbreaking trial, six patients with treatment-refractory rheumatoid arthritis (RA) received CD19 CAR T-cell therapy, which targets disease-driving B cells. The results, published in Nature Medicine, show that all participants experienced significant reductions in disease activity, with three remaining in remission without medication for up to one year.
The Trial and Its Groundbreaking Approach
The trial, led by researchers at Charité-Universitätsmedizin Berlin, focused on patients with severe RA who had exhausted conventional treatments. The therapy involves modifying patients’ own T cells to target CD19, a marker on B cells linked to autoimmune inflammation. One reason could be disease-driving B cells—memory cells of the adaptive immune system that may survive in the lymph nodes, bone marrow or joint tissue after an infection, where they produce harmful antibodies,
explained Prof. David Simon, a key researcher on the project.
The process begins with collecting T cells from the patient’s blood, genetically modifying them to recognize CD19, and then reinfusing them. This approach temporarily eliminates CD19-positive B cells, including long-lived disease-driving cells in joints. To enable CAR T cells to detect and eliminate the disease-causing cells, we equip patients' own immune cells with a receptor that acts like a search sensor for CD19,
Simon said. The therapy also included preparatory chemotherapy to create space for the modified cells to proliferate.
Safety and Efficacy Outcomes
The trial, named COMPARE, evaluated both safety and efficacy. Primary endpoints included the incidence of cytokine release syndrome (CRS) and other adverse events. Researchers reported that all six patients experienced only mild-to-moderate CRS, which was manageable, with no severe neurological complications or serious infections. This is particularly remarkable given that none of the established treatments had previously been able to relieve their symptoms adequately,
said Dr. Gerhard Krönke, a co-leader of the study.
Follow-up data showed that three patients remained in sustained remission without RA medication for up to 52 weeks. Autoantibody levels, a key marker of RA activity, also declined sharply. Disease activity decreased markedly in all six patients,
the study noted.
Implications for Autoimmune Disease Treatment
The findings suggest a potential shift in how autoimmune diseases are managed. Current RA treatments often focus on suppressing inflammation rather than addressing its root causes. CAR T-cell therapy, by targeting B-cell memory, offers a new approach to resetting the immune system.
Challenges and Future Research
While the results are promising, challenges remain. The therapy is still experimental, with limited long-term data. CAR T-cell therapy for autoimmune diseases remains experimental.
There is not yet any long-term experience with this treatment,
the study noted.
The trial represents a significant step forward in harnessing immunotherapy for autoimmune diseases. By targeting the root mechanisms of RA, CD19 CAR T-cell therapy could offer a transformative alternative to lifelong medication. As research progresses, the medical community awaits further evidence of its potential to redefine treatment paradigms for chronic autoimmune conditions.
