Results of a 1-year randomised double-blind placebo-controlled trial with methotrexate 25 mg/week in recently diagnosed polymyalgia rheumatica.

Abstract

OBJECTIVES: Methotrexate is recommended in current guidelines as a first-choice glucocorticoid (GC)-sparing agent for patients with polymyalgia rheumatica (PMR) prone to relapses or prolonged GC use. Previous randomised controlled trials (RCTs) have reported conflicting results but used low doses of methotrexate (7.5-10 mg/wk). More evidence on higher doses (25 mg/wk) is needed.

METHODS: In this 52-week blinded, placebo-controlled RCT, patients with recently diagnosed PMR (per 2012 European League Against Rheumatism/American College of Rheumatology criteria) and <8 weeks of GC use were randomised 1:1 to methotrexate 25 mg/wk or placebo, alongside a 24-week GC-tapering protocol. The primary outcome was GC-free remission (Polymyalgia Rheumatica-Activity Score <10 and no GC use) at week 52, tested with a 1-sided Cochran-Mantel-Haenszel test stratified by sex and inflammatory markers.

RESULTS: Sixty-four patients were recruited, of whom 58 were included in the final analysis. GC-free remission at 52 weeks was achieved in 80% of patients in the methotrexate group vs 46% in the placebo group (risk difference 34%, 1-sided 95% CI: 14%, 1-sided P = .0042).

CONCLUSIONS: This small but high-quality RCT demonstrated that methotrexate 25 mg/wk significantly increases the likelihood of achieving GC-free remission at 52 weeks in newly diagnosed PMR. These findings show a benefit of early introduction of methotrexate in PMR. Further research is needed to determine the optimal timing of methotrexate initiation.