Prednisone plus Methotrexate for Polymyalgia Rheumatica

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The summary below is from the full report titled "Prednisone plus Methotrexate for Polymyalgia Rheumatica. A Randomized, Double-Blind, Placebo-Controlled Trial." It is in the 5 October 2004 issue of Annals of Internal Medicine (volume 141, pages 493-500). The authors are R. Caporali, M.A. Cimmino, G. Ferraccioli, R. Gerli, C. Klersy, C. Salvarani, and C. Montecucco, for the Systemic Vasculitis Study Group of the Italian Society for Rheumatology.

What is the problem and what is known about it so far?

Polymyalgia rheumatica is a condition characterized by pain and stiffness in the muscles around the shoulders and hips. The cause is unknown. Polymyalgia rheumatica most often occurs in women older than 50 years of age. In addition to muscle pain, some patients with polymyalgia rheumatica have a sense of feeling unwell (malaise), fatigue, fever, night sweats, or weight loss. Doctors usually treat polymyalgia rheumatica with oral corticosteroids (prednisone). Prednisone relieves symptoms, but patients often need to take it for a long time, and long-term use may cause side effects, such as bone loss. Thus, doctors and patients would like to find a way to treat polymyalgia rheumatica that decreases the need for long-term prednisone therapy.

Why did the researchers do this particular study?

To see whether combined treatment with prednisone plus methotrexate (an antirheumatic drug that suppresses the immune system) improves symptoms and decreases long-term use of prednisone in patients with polymyalgia rheumatica.

Who was studied?

72 adults with newly diagnosed polymyalgia rheumatica from 5 rheumatology clinics in Italy.

How was the study done?

Participants were randomly assigned to take 48 weekly oral doses of either methotrexate (10 mg) or placebo (matching dummy pills). All patients were given oral prednisone (25 mg/d) that was tapered and discontinued within 24 weeks if patients had no polymyalgia rheumatica symptoms. Prednisone therapy was continued or restarted if patients reported symptoms. All patients were also given weekly folinic acid supplements (7.5 mg) for 48 weeks because methotrexate depletes levels of this vitamin. Neither the researchers nor the participants knew who received methotrexate or placebo. Participants were monitored for flare-ups of symptoms at regularly scheduled clinic visits. At 76 weeks, the researchers compared the numbers of polymyalgia rheumatica flare-ups and the overall use of prednisone between the 2 groups.

What did the researchers find?

Patients assigned to prednisone plus methotrexate had fewer flare-ups, used a smaller total dose of prednisone, and more often remained off prednisone at the end of the study than did those assigned to prednisone alone. Similar numbers of patients in both groups reported side effects, although some symptoms, such as stomach upset, appeared to be more common among patients given methotrexate.

What were the limitations of the study?

Patients were followed for only a year and a half, and 14% did not complete follow-up.

What are the implications of the study?

Initial treatment with prednisone plus methotrexate may decrease the need for long-term steroid therapy in patients with polymyalgia rheumatica.