Steroid‐sparing effects of methotrexate in systemic lupus erythematosus: A double‐blind, randomized, placebo‐controlled trial

• Published in: Arthritis and rheumatism 2008-12, Vol.59 (12), p.1796-1804
• Main Authors: Fortin, Paul R., Abrahamowicz, Michal, Ferland, Diane, Lacaille, Diane, Smith, C. Douglas, Zummer, Michel
• Format: Article
• Language: English
• Subjects: Adult; Antirheumatic Agents - therapeutic use; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Diseases of the osteoarticular system; Double-Blind Method; Female; Humans; Lupus Erythematosus, Systemic - drug therapy; Male; Medical sciences; Methotrexate - administration & dosage; Methotrexate - therapeutic use; Middle Aged; Pharmacology. Drug treatments; Prednisone - administration & dosage; Research Design; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Steroids - administration & dosage
• ISSN: 0004-3591; 0893-7524; 1529-0131; 1529-0123
• DOI: 10.1002/art.24068

Objective To assess the potential benefits of methotrexate in patients with systemic lupus erythematosus (SLE). Methods A 12‐month, double‐blind, placebo‐controlled trial of methotrexate with folic acid was conducted. Intent‐to‐treat analyses were performed with mixed linear models and α = 0.04 (96% confidence interval [96% CI]) to account for interim analysis of longitudinal data to assess the treatment effects on lupus disease activity and daily steroid dose across monthly measurements, and to test if the treatment effects depended on selected participant characteristics. Results Of 215 participants screened, 94 were excluded, 35 declined, and 86 were randomized (methotrexate = 41, placebo = 45). The groups were balanced for demographic and disease characteristics. Antimalarial use was more frequent in the placebo group, which was adjusted for in multivariable analyses. Sixty participants (27 methotrexate, 33 placebo) completed the study and 26 terminated early. Among participants who had the same baseline prednisone dose, those taking methotrexate received, on average, 1.33 mg/day less prednisone during the trial period (96% CI 0.06, 2.72 mg/day; a 22% reduction of their average‐during‐trial daily dose) compared with those in the placebo group. For the primary measure of disease activity (revised Systemic Lupus Activity Measure), methotrexate use was also associated with a marginally significant reduction in the mean during‐trial score of 0.86 units (96% CI 0.01, 1.71; P = 0.039). A significant interaction between treatment and baseline damage was found (P = 0.001). Conclusion Methotrexate conferred a significant advantage in participants with moderately active lupus by lowering daily prednisone dose and slightly decreasing lupus disease activity. As a therapeutic option in moderate SLE, methotrexate can be considered to be steroid sparing.