Steroids are the standard treatment for polymyalgia rheumatica. The efficacy of the candidate drug methotrexate has not yet been demonstrated in controlled studies.

To compare the efficacy and safety of prednisone plus methotrexate and prednisone alone in patients with polymyalgia rheumatica.

Multicenter randomized, double-blind, placebo-controlled trial.

5 Italian rheumatology clinics.

72 patients with newly diagnosed polymyalgia rheumatica.

The proportion of patients no longer taking prednisone, the number of flare-ups, and the cumulative prednisone dose after 76 weeks.

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.

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% CI, 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.

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.

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.