Six treatment-refractory patients experienced substantial drops in disease activity, with half stopping all medication entirely.
Immunotherapies such as CAR-T cell therapy were originally built to fight cancer. But scientists are now investigating whether these personalized treatments, made from a patient’s own immune cells, could help treat autoimmune diseases, according to findings from the COMPARE trial reported in Nature Medicine.
Researchers at Charité – Universitätsmedizin Berlin tested the approach on six people with particularly severe rheumatoid arthritis. According to the data, disease activity fell substantially in every participant. By the end of the observation period, three patients no longer needed rheumatoid arthritis medication.
“Disease activity decreased markedly in all six patients,” said Gerhard Krönke, who leads the joint Clinical Rheumatology research group at Charité and the German Rheumatology Research Center (DRFZ), a Leibniz Institute, according to the study. “During follow-up of up to one year, three patients were in sustained remission without any medication for rheumatoid arthritis.”
Why Treatment-Refractory Rheumatoid Arthritis Resists Standard Care
Rheumatoid arthritis is a chronic autoimmune disease in which the immune system mistakenly attacks the joints. Repeated inflammation causes swelling and can eventually damage the joints, according to study documentation.
Existing medications control inflammation well for many patients, but they generally do not cure the disease. Consequently, many patients require lifelong treatment with anti-inflammatory drugs and immunosuppressants, which bring side effects.
For some patients, even newer therapies fail to work. Doctors describe these cases as treatment-refractory rheumatoid arthritis. Patients continue to experience pain, limited mobility, and major reductions in quality of life.
“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,” explained Prof. David Simon, who designed the trial for this patient group alongside Prof. Gerhard Krönke at Charité’s Department of Rheumatology and Clinical Immunology.
How Engineering Patient T Cells Resets Immune Memory
To produce this form of CD19 CAR-T cell therapy—specifically evaluated in the trial as mivocabtagene autoleucel (miv-cel)—doctors first collect T cells from the patient’s blood. Scientists then genetically modify those T cells in the laboratory.
The cells receive an artificial antigen receptor known as a CAR, which binds specifically to CD19, a surface molecule found on abnormal B cells. Before receiving the modified cells, patients undergo a short course of preparatory lymphodepletion chemotherapy.
“The identifying marker on many B cells, both abnormal B cells in cancers of the blood or lymphatic system and disease-driving B cells in rheumatoid arthritis, is the surface molecule CD19,” said David Simon. “You could think of it as a kind of ‘name tag’.”
Once infused back into the patient, the engineered cells search for targets carrying CD19. This temporarily removes all CD19-positive B cells, clearing out deep reservoirs in the joints, lymph nodes, and bone marrow.
Clinical Trial Results and Safety Findings
The COMPARE trial enrolled three women and three men aged 31 to 69. Over the preceding decade, they had received up to eight targeted or biologic therapies without adequate disease control.
Following a single infusion of miv-cel after stopping prior disease-modifying antirheumatic drugs, all six anti-citrullinated protein antibody (ACPA)-positive patients were followed for 36 to 52 weeks. Levels of disease-associated autoantibodies dropped sharply across the cohort.
“When the B-cell system later recovered, predominantly naïve B cells that had not yet been shaped by the disease returned,” David Simon noted. Meanwhile, protective antibody memory from earlier vaccinations like chickenpox and tetanus remained largely preserved.
Regarding safety, Dr. Marie Luise Hütter-Krönke, Medical Director of the Hematology Early Clinical Trial Unit at Charité, stated that researchers observed “only a temporary, mild-to-moderate cytokine release syndrome (CRS) in all participants, which was readily manageable.” There were no severe neurological complications or other serious adverse events, and infections were rare.
Did you know? CAR-T cell therapy uses a patient’s own harvested immune cells, genetically altering them with a receptor designed to hunt down the specific surface markers driving chronic inflammation.
Frequently Asked Questions
What is CAR-T cell therapy for rheumatoid arthritis?
It is an experimental immunotherapy where a patient’s T cells are modified in a lab to target and destroy CD19-positive B cells that drive chronic joint inflammation.
How many patients achieved remission in the Charité trial?
Out of six treatment-refractory patients enrolled in the world-first trial published in Nature Medicine, three entered sustained remission and stopped taking all rheumatoid arthritis medications during the follow-up period.
Is CAR-T cell therapy approved for rheumatoid arthritis?
No. While the early phase results are encouraging, the treatment remains experimental, and researchers are preparing a second phase to compare CAR-T cells against approved biologic therapies.
What are the common side effects observed so far?
According to study investigators, participants experienced temporary, mild-to-moderate cytokine release syndrome (CRS) that was easily managed, with no severe neurological complications or frequent infections.
What are your thoughts on using cancer immunotherapies to treat autoimmune disorders? Share your perspective in the comments below, or subscribe to our newsletter for updates on the next phase of the COMPARE trial.
Related reading