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Methotrexate and Polymyalgia Rheumatica Therapy



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Am Fam Physician. 2005 Sep 1;72(5):891-892.

Polymyalgia rheumatica, a syndrome characterized by proximal muscle pain and stiffness in older persons, generally is treated with prednisone (Deltasone). Dosages of 15 to 25 mg of prednisone per day can reduce inflammation considerably, although many patients relapse when therapy is tapered. Long-term (18 to 36 months) steroid treatment has been recommended by several studies, but this can result in multiple side effects, including osteoporosis, hypertension, cataracts, and hyperglycemia. Methotrexate (Rheumatrex) has been used to reduce inflammation in rheumatoid arthritis, systemic vasculitis, and giant cell arteritis, and in small studies has been combined with prednisone to treat polymyalgia rheumatica, decreasing the duration of treatment. Caporali and associates conducted a multicenter, double-blind, randomized controlled trial to evaluate the efficacy of methotrexate when combined with prednisone in the wide-scale treatment of polymyalgia rheumatica.

Seventy-two patients with polymyalgia rheumatica and no contraindications to prednisone or methotrexate were given prednisone at a daily dosage of 25 mg for four weeks, tapering to 17.5 mg, 12.5 mg, 7.5 mg, 5 mg, and 2.5 mg during the following five four-week periods. In addition, patients were randomly assigned to receive methotrexate (10 mg per week) or placebo. Relapses were treated by resumption of the dose of the previous period. After 24 weeks, prednisone treatment was discontinued. All participants received a weekly dose of folinic acid (7.5 mg) 24 hours after administration of methotrexate or placebo, and daily doses of oral calcium (1 g) and vitamin D3 (800 IU). Patients were assessed regularly during the 76 weeks of the study. Medications were withdrawn from patients if there was a significant decrease in their leukocyte or platelet count or a significant increase in their serum creatinine or transaminase levels.

At the end of the study, 32 patients (89 percent) in the methotrexate group and 30 (83 percent) in the placebo group were available for evaluation. More patients in the methotrexate group were free of steroids after 76 weeks than in the placebo group, even when the worst-case scenario was assumed for those who dropped out. The efficacy of methotrexate was clear after 48 weeks, and the methotrexate patients also had significantly fewer flare-ups. Adverse reactions were not significantly different between the two trial groups.

The authors conclude that using prednisone and methotrexate together to treat polymyalgia rheumatica can decrease the number of flare-ups and reduce the total dosage of prednisone required to achieve and maintain remission. Considering the potential adverse effects of long-term prednisone therapy, this would be advantageous to all patients, especially those who cannot tolerate high doses of prednisone. Further studies are needed to determine whether methotrexate is effective as an induction therapy for polymyalgia rheumatica, and whether it can lower the initial dose of prednisone needed for treatment and control.

Caporali R, et al. Prednisone plus methotrexate for polymyalgia rheumatica. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. October 5, 2004;141:493–500.

editor’s note: In an editorial in the same journal,1 Stone points out that prior studies on the prednisone-sparing effect of methotrexate in polymyalgia rheumatica and the related disorder giant cell arteritis have been inconclusive. Even in the Caporali study, doubt is cast on the efficacy of methotrexate because the methotrexate group had fewer flare-ups during weeks 48 to 76 when they were no longer taking methotrexate, and the likelihood of methotrexate having such a sustained effect is low. Also, the absence of increased steroid morbidity in the higher-dose prednisone plus placebo group makes the clinical significance of this minimal prednisone dose reduction unclear. Lastly, the lack of difference in disease flare-ups during the first 24 weeks when all participants were taking prednisone, and the occurrence of flare-ups in the methotrexate group after prednisone was withdrawn, seems to demonstrate that this effectiveness was caused by prednisone alone rather than the combination. Perhaps the continuation of the lowest effective dose of prednisone (5 mg or less) would be the best and simplest treatment. Stone concludes that methotrexate may be useful for patients who do not tolerate even low doses of glucocorticoids, but the combination requires further study.—r.s.

 

REFERENCE

1. Stone JH. Methotrexate in polymyalgia rheumatica: kernel of truth or curse of Tantalus? Ann Intern Med. 2004;141:568–9.



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