“Remission even after stopping medication”: CAR T-cell therapy improves refractory rheumatoid arthritis in 3 patients

Clinical results show that three patients with refractory rheumatoid arthritis maintained symptom remission after stopping medication following CAR T-cell therapy.

According to BioOn on the 14th local time, researchers at Charité – Universitätsmedizin Berlin in Germany published phase 1 results for CD19 CAR T-cell therapy in rheumatoid arthritis in the journal Nature Medicine.

The researchers treated six patients with severe rheumatoid arthritis that had not responded to existing treatments. The group included three women and three men, ages 31∼69, who had received up to eight targeted and biologic therapies over the past 10 years but had not achieved an adequate response.

As a result, disease activity decreased substantially in all participants. During follow-up of up to 1 year, three maintained sustained remission without rheumatoid arthritis medication.

“This is particularly noteworthy given that none of the existing treatments had previously been able to adequately relieve their symptoms,” said Professor Gerhard Krönke.

Rheumatoid arthritis is a chronic disease in which the immune system attacks the body’s own joints. Current treatments control inflammation but do not cure the disease, so patients must take medication for life.

The researchers targeted B cells that drive the disease. “There is a molecule called CD19 on the surface of the B cells that cause the disease,” said Professor David Simon. “We equipped the patients’ immune cells with receptors that recognize CD19 so they could eliminate pathogenic cells.”

For the treatment, T cells were collected from each patient’s blood, genetically modified and then returned in a single intravenous infusion. Before the infusion, patients received a short course of preparatory chemotherapy to make room in the immune system.

During 12 months of follow-up after treatment, levels of autoantibodies characteristic of rheumatoid arthritis fell sharply. “When B cells recovered, they were mainly naive B cells that had not been exposed to the disease, while the autoreactive B cells present before treatment were almost undetectable,” Professor Simon said.

Protective antibodies generated by existing vaccines, such as those for chickenpox and tetanus, were maintained. However, further research is needed to assess the long-term effects on the immune system.

In terms of safety, all participants experienced only transient, mild cytokine release syndrome (CRS). “There were no serious neurologic complications or serious adverse events, and infections were rare,” said Dr. Marie-Louise Huetter-Kroenke.

However, responses varied among patients. Some did not achieve complete remission, and one patient’s disease relapsed after a period of drug-free remission.

The researchers plan to compare the treatment with existing B-cell-targeting drugs in a phase 2 study involving 10 additional patients. The goal is to determine whether CAR T-cell therapy produces a stronger and more durable effect.