INTERVENTION WITH METHOTREXATE IN ARTHRALGIA AT RISK FOR RHEUMATOID ARTHRITIS TO REDUCE THE DEVELOPMENT OF PERSISTENT ARTHRITIS AND ITS DISEASE BURDEN (TREAT EARLIER): A DOUBLE-BLIND, RANDOMISED, PLACEBO-CONTROLLED TRIAL
Authors: D. Krijbolder, et al.
In recent years, many trials have explored the efficacy of treating «pre-clinical rheumatoid arthritis (RA)», or patients at very high risk to develop clinical RA in order to prevent the disease. The trials presented so far have essentially been with biotherapies, such as rituximab or abatacept.
The ‘Treat-Earlier’ is a large randomized trial from the Netherlands that randomized 236 individuals with arthralgia clinically suspected of progressing to RA and signs of subclinical joint inflammation. Participants received either a single injection of glucocorticoids + methotrexate (MTX), or placebo (PBO) for one year. The patients were followed-up for another 12 months and examined for the development of inflammatory arthritis. In the overall population, there was no difference in arthritis free survival (80% versus 82%, HR 0.81 (95%CI 0.45, 1.48)). High-risk participants and ACPA-positive participants demonstrated a delay in clinical arthritis development.
This trial is remarkable in many aspects: 1. It’s a larger trial in a difficult population to enroll in trial as these are not the typical rheumatic patients; 2. the authors used a conventional DMARD, not a biotherapy (which means probably not industry funding). From a clinician, from a patient and from public health point of view this makes sense, as we are unlikely to propose a biotherapy to patients with clinically suspected arthralgias. Unfortunately, while MTX is able to delay RA development in people with imminent RA, it does not seem to prevent it. Similar results were seen 15 years ago in a trial of patients with early unclassifiable arthritis.
Another learning point from this study is that we should consider prescribing DMARDs only to arthralgia patients at very high risk of developing RA, which generally include positive ACPAs and typical inflammatory arthralgias of small joints.