Prednisone plus methotrexate for polymyalgia rheumatica: a randomized, double-blind, placebo-controlled trial

Ann Intern Med. 2004 Oct 5;141(7):493-500. doi: 10.7326/0003-4819-141-7-200410050-00005.


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% 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.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Placebos
  • Polymyalgia Rheumatica / drug therapy*
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Prednisone / therapeutic use*


  • Anti-Inflammatory Agents
  • Antirheumatic Agents
  • Placebos
  • Leucovorin
  • Prednisone
  • Methotrexate