Cancer Therapy Put Severe Rheumatoid Arthritis Into Remission in World-First Trial

Doctors at Charité - Universitätsmedizin Berlin have tested CAR T-cell therapy, a treatment originally developed for cancer, in six patients with particularly severe rheumatoid arthritis, in what researchers describe as the world's first clinical trial of its kind. The results, reported in Nature Medicine, were encouraging: disease activity fell substantially in every participant, and three of the six no longer needed rheumatoid arthritis medication by the end of the observation period.

Rheumatoid arthritis is a chronic autoimmune disease in which the immune system mistakenly attacks the joints, causing repeated inflammation that can eventually damage bone and joint tissue. Existing medications can control the inflammation but generally do not cure the disease, and some patients do not respond well even to newer targeted therapies — a condition doctors call treatment-refractory rheumatoid arthritis.

"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 directed against the body's own tissues and repeatedly reignite the inflammation," said Prof. David Simon, who designed the trial together with Prof. Gerhard Krönke at Charité's Department of Rheumatology and Clinical Immunology.

The therapy targets CD19, a marker found on many B cells, including both cancerous B cells and the disease-driving B cells implicated in rheumatoid arthritis. To produce the treatment, doctors collect T cells from a patient's blood and genetically modify them in the laboratory to carry a chimeric antigen receptor (CAR) that binds to CD19. After a short course of preparatory chemotherapy, the engineered cells are returned to the patient in a single infusion, where they seek out and destroy CD19-positive cells, including long-lived disease-driving B cells hidden deep in the joints.

The first phase of the trial, called COMPARE, enrolled six patients with especially severe disease — three women and three men aged 31 to 69 — who had received as many as eight targeted or biologic therapies over the previous decade without adequate relief. "Disease activity decreased markedly in all six patients. During follow-up of up to one year, three patients were in sustained remission without any medication for rheumatoid arthritis," reported Prof. Gerhard Krönke, who leads the joint Clinical Rheumatology research group at Charité and the German Rheumatology Research Center (DRFZ).

Researchers found that the modified immune cells also reached and eliminated disease-promoting B cells in the bone marrow, lymph nodes, and joint tissue, and that levels of the autoantibodies associated with rheumatoid arthritis dropped sharply during the 12-month follow-up. According to Prof. David Simon, when the B-cell system later recovered, it was made up mostly of naive B cells that had not yet been shaped by the disease, while the autoreactive B cells present before treatment were no longer detectable.