Novel therapy for rheumatoid arthritis studied in healthy participants and in patients

‘In 2025, we demonstrated that our work with healthy participants can also contribute to the development of innovative therapies for RA,’ says Dr Naomi Klarenbeek, Research Director Internal Medicine. The study was conducted in collaboration with the Rheumatology Department at LUMC, where the same drug was then tested in patients with rheumatoid arthritis.

The new treatments for autoimmune diseases such as SLE and RA build on the discovery that these diseases can be brought into long-term remission by ‘resetting’ the immune system through broad B-cell depletion. ‘The major breakthrough came a few years ago, when it was demonstrated that CAR-T cells against the B-cell compartment brought the disease into remission in patients with severe, long-standing SLE,’ says Klarenbeek. Chimeric antigen receptor (CAR) T-cells can specifically eliminate the antibody-producing B cells of the immune system. ‘For a short while, the patient is then more vulnerable to infections, but the risk is not too great. The B cells are quickly replenished from the bone marrow. And remarkably, the autoimmunity does not return; in any case, the disease remains in remission for a long time,’ says Klarenbeek.

B-cell depletion has also been shown to be effective against rheumatoid arthritis. Bispecific antibodies are capable of achieving temporary B-cell depletion in a way similar to CAR-T cells. Other innovative immunological compounds are also in development, building on the novel insights into autoimmune diseases.

CHDR has extensive experience in the early phase clinical development of immunological compounds, but each one comes with its own challenges. In 2025, a new immunological compound was tested which aims to treat rheumatoid arthritis. In collaboration with researchers at the LUMC’s Rheumatology Department, the compound could be tested in both healthy participants and in patients.

The first Single Ascending Dose studies were conducted at CHDR in healthy study participants. After the first four cohorts, once we had established the dosage at which the drug had a measurable effect, the study was continued with the same protocol in patients at the LUMC. A similar study was performed in collaboration with the Haga Hospital in The Hague.

Klarenbeek: ‘This design means that patients are only given doses that can actually have an effect, reducing the burden on patients. The detailed information we obtained about the compound’s pharmacology added to the safety and scientific value of the studies in patients as well. We knew we could safely study this compound in healthy participants. Of course, we monitor their health closely and only move on to a higher dosage once we have all the results. Everything worked out as expected. So together with our colleagues at the LUMC and Haga Hospital, we have demonstrated that we can carry out the clinical development process from first-in-human to patient studies.’