STEp-down approach in MEthotrexate use for the Treatment of Rheumatoid Arthritis (STEMETRA): a pilot study demonstrating efficacy and safety of short-term, high dose methotrexate.

Objectives: Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment, showing a suitable efficacy-safety profile, relatively low-cost, and versatile dosages and routes of administration. However, there are no clear indications yet on the optimal use of MTX in RA, whereas existing recommendations disagree on relevant aspects. STEMETRA is a 16-week open-label, monocentric, pilot study aimed at evaluating the efficacy and the safety of a step-down strategy of using subcutaneous (sc) MTX in patients with RA.

Methods: The study consists of the administration of a starting dose of MTX 50 mg sc/week for 4 weeks, to be subsequently reduced to 15 mg/week in a 12-week period. Fifteen RA patients naive to any disease specific therapy were enrolled.

Results: One patient was lost to follow-up after week 12, 4 patients withdrew because of adverse events, therefore, 10 patients concluded the study. Mean DAS28(CRP) at baseline was 5.6 (±0.37 SE), whereas, at week 16, mean DAS28(CRP) was 1.6 (±0.41SE). Most patients who concluded the study achieved ACR70 response and remission (7 out of 10), whereas three still showed moderate disease activity.

Conclusions: In this study, the step-down MTX approach was effective in inducing remission in most of the patients enrolled, without increasing the risk of adverse events. Thus, short-term higher dosages of MTX could be more effective in reaching remission earlier. Nonetheless, these results should be confirmed in larger populations of patients.