Early Methotrexate initiation before patients develop rheumatism provides lasting relief: Lancet

Early treatment benefits patients who have not fully developed rheumatoid arthritis but are in the preliminary stages of the disease. This is what researchers from the Leiden University Medical Centre (LUMC) have reported in The Lancet. Patients in the pre-arthritis stage who were temporarily prescribed methotrexate experienced a sustained reduction in joint inflammation, pain and physical limitations.

'At present, methotrexate is only prescribed to patients who have been diagnosed with rheumatoid arthritis,' explains Professor of Rheumatology, Annette van der Helm. 'But that is too late. By then, the disease is already chronic.' The researchers hoped to prevent or reduce the disease burden by giving methotrexate to patients who had not yet developed rheumatoid arthritis but were likely to.

Step in the right direction

The study showed that although the early treatment did not prevent the development of rheumatoid arthritis, the diagnosis was delayed. Furthermore, the patient group that had been temporarily prescribed methotrexate experienced a sustained reduction in pain, morning stiffness and restrictions in everyday life. Less joint inflammation was also apparent on the MRI scans.

'Although this didn't prevent rheumatoid arthritis, it is an important step towards reducing the disease burden for this group of patients,' says Van der Helm. 'And this is the first evidence that starting treatment in the pre-arthritis stage can be worthwhile.'

The study was carried out within the Medical Delta organisation and received funding from ZonMw and ReumaNederland. It took eight years and included over 230 patients. 'They all suffered from joint pain and inflammation, which could be seen on the MRI and was thought to be an early sign of rheumatoid arthritis,' says PhD candidate Doortje Krijbolder.

However, rheumatologists do not know for certain whether someone will go on to develop rheumatoid arthritis. These pre-arthritis patients were treated with methotrexate or a placebo for a year and were followed for a further year to see if the effects of the treatment persisted.

Best treatment

Rheumatoid arthritis is the most common autoimmune disease in the world. It causes the immune system to attack the joints and the usual treatment only suppresses the disease.

'This chronic disease has a significant impact on the lives of patients and their families. Our study is paving the way toward arthritis prevention,' says Van der Helm. 'To achieve this, we need a better understanding of the molecular processes that are responsible for the chronic nature of this disease.

Reference:

Doortje I Krijbolder, Marloes Verstappen, Bastiaan T van Dijk, Yousra J Dakkak, Leonie E Burgers, Aleid C Boer, Yune Jung Park, Marianne E de Witt-Luth, Karen Visser, Marc R Kok, Esmeralda T H Molenaar, Pascal H P de Jong, Stefan Böhringer, Prof Tom W J Huizinga,Cornelia F Allaart, Ellis Niemantsverdriet, Prof Annette H M van der Helm-van Mil, Published:July 23, 2022 DOI: https://doi.org/10.1016/S0140-6736(22)01193-X