by Leiden University Medical Centre

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Initiating early treatment benefits patients who have not fully developed rheumatoid arthritis, but who are manifesting preliminary stages of the disease. This is what researchers from the Leiden University Medical Centre (LUMC) have reported in The Lancet. By temporarily prescribing methotrexate in the "pre-rheumatic phase," patients suffer from reduced long-term joint inflammations, pain and physical limitations.

"At present, methotrexate is only prescribed to the patient following a rheumatoid arthritis diagnosis," explains Annette van der Helm, Professor of Rheumatology. "But that is too late. By then, the disease is already considered chronic." The researchers hope to prevent or reduce disease burden by giving methotrexate to patients likely to develop rheumatoid arthritis.

Step in the right direction

Although early treatment did not completely prevent the development of rheumatoid arthritis, the research group found that diagnosis was delayed. Furthermore, the patient group that had been temporarily prescribed methotrexate endured less pain, morning stiffness and daily functioning impediments. MRI scans also showed fewer joint inflammations. "This is an important step towards reducing disease burden for this group of patients," says Van der Helm. Moreover, it serves as initial evidence for initiating treatment in the 'pre-rheumatic' phase."

The study, carried out within Medical Delta and over a period of 8 years, included more than 230 patients. "All suffered from joint pain and inflammation, which could be seen on the MRI, and was thought to be a rheumatism precursor," says Ph.D. student Doortje Krijbolder. However, rheumatologists do not know for certain whether this is truly the case. Pre-rheumatoid patients were treated with methotrexate or a placebo for one year. Another one year follow-up enabled researchers to see if the effects of the treatment persisted.

Optimal treatment

Rheumatoid arthritis is the most common autoimmune disease worldwide. It causes the immune system to attack the joints. Usual treatment only suppresses the disease. "This chronic disease is extremely burdensome to patients and their families. Our study is paving the way toward arthritis prevention," says Van der Helm. "To achieve this completely, greater understanding of the molecular processes underlying the chronic nature of rheumatoid arthritis is necessary."

More information: Doortje I Krijbolder et al, Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial, The Lancet (2022). DOI: 10.1016/S0140-6736(22)01193-X

Journal information: The Lancet 

Provided by Leiden University Medical Centre