A prospective, double-blind, randomized, placebo controlled trial of methotrexate in the treatment of giant cell arteritis (GCA)

Objective To determine if methotrexate has disease-controlling and corticos teroid (cs)-sparing effects in the treatment of giant cell arteritis (GCA). Methods This was a randomized, controlled, double-blind trial comparing met hotrexate versus placebo in addition to corticosteroid therapy in patients with newly diagnosed giant cell arteritis. Patients with giant cell arterit is were enrolled and treated with high dose corticosteroids as well as meth otrexate starting at 7.5 mg/week or placebo. Corticosteroids were tapered b y the treating physician as guided by the clinical picture, with methotrexa te or placebo dose increased by 2.5 mg/week for disease flare with a maximu m allowable dose of 20 mg/week. After a clinically-defined remission and st eroid discontinuation, methotrexate or placebo was tapered monthly to zero by 2.5 mg/week. Results Twenty-one patients were enrolled, 12 randomized to methotrexate, 9 to placebo. Baseline characteristics (age, height, weight, sedimentation r ate, bone mineral density, total corticosteroid dose prior to randomization , and quality of life as measured by SF-36 and function as measured by AIMS ) were comparable between groups. At completion, there was no significant d ifference between methotrexate-and placebo-treated patients with regard to the cumulative corticosteroid dose (6469 mg and 5908 mg respectively, p=0.6 ), number of weeks to completion of steroids (68 and 60 respectively, p=0.5 ), time (weeks) to taper prednisone to less than 10 mg prednisone/day (23 a nd 25 respectively, p=0.5), bone mineral density in lumbar spine (p=0.2) or hip (p=0.4) at one year, or functional status as measured by AIMS and qual ity of life as measured by SF36. There was no late vision loss in either gr oup, and only one major treatment-responsive relapse in a methotrexate-trea ted patient. There were few major corticosteroid-related side effects and t hese did not significantly differ between groups. Conclusion With this study design, no corticosteroid-sparing benefit could be attributed to the combination of methotrexate with corticosteroid therap y for the treatment of patients with giant cell arteritis. Both groups did well, with few major corticosteroid-related side effects, and most patients were safely tapered off corticosteroids sooner than reported in many serie s. The shorter overall duration of steroid treatment in this study probably contributed to the remarkably low frequency of side effects, without incre ased ischemic risk for the patient.