Prednisone plus Methotrexate for polymyalgia rheumatica. A randomized, double blind, placebo-controlled trial

Background: Steroids are the standard treatment for polymyalgia rheumatica. The efficacy of the candidate drug methotrexate has not yet been demonstrated in controlled studies. Objective: To compare the efficacy and safety of prednisone plus methotrexate and prednisone alone in patients with polymyalgia rheumatica. Design: Multicenter randomized, double-blind, placebo-controlled trial. Setting: 5 Italian rheumatology clinics. Patients: 72 patients with newly diagnosed polymyalgia rheumatica. Measurements: The proportion of patients no longer taking prednisone, the number of flare-ups, and the cumulative prednisone dose after 76 weeks. Intervention: Prednisone dosage (25 mg/d) was tapered to 0 mg/d within 24 weeks and was adjusted if flare-ups occurred. Oral methotrexate (10 mg) or placebo, with folinic acid supplementation (7.5 mg), was given weekly for 48 weeks. Results: Twenty-eight of 32 patients in the methotrexate group and 16 of 30 patients in the placebo group were no longer taking prednisone at 76 weeks (P = 0.003). The risk difference was 34 percentage points (95% Cl, 11 to 53 percentage points). Similar results were obtained after adjustment for C-reactive protein level and duration of symptoms in a multivariate model. Fifteen of 32 patients in the methotrexate group and 22 of 30 patients in the placebo group had at least 1 flare-up by the end of follow-up (P = 0.04). The median prednisone dose was 2.1 g In the methotrexate group and 2.97 g in the placebo group (P = 0.03). The rate and severity of adverse events were similar. Limitations: Follow-up was short, and a high dose of folinic acid and a relatively high starting dosage of prednisone were used. Ten of 72 patients (14%) discontinued treatment or were lost to follow-up. Conclusions: Prednisone plus methotrexate is associated with shorter prednisone treatment and steroid sparing. It may be useful in patients at high risk for steroid-related toxicity.