Comparative Efficacy of Methotrexate Versus Cyclosporine in the Treatment of Moderate-to-Severe Chronic Plaque Psoriasis: A Systematic Review and Meta-Analysis

The relative efficacy of methotrexate versus cyclosporine in the treatment of moderate-to-severe chronic plaque psoriasis remains controversial. This systematic review and meta-analysis evaluates the effectiveness of methotrexate compared to cyclosporine for psoriasis patients. From inception through April 2025, PubMed, Cochrane, Embase, and Google Scholar were searched for randomized controlled trials (RCTs) comparing methotrexate with cyclosporine in patients with chronic plaque psoriasis. A random effects model was used. Primary outcomes were reduction in Psoriasis Area and Severity Index (PASI) score at different follow-ups, PASI 75, and PASI 90. Secondary outcomes included patient-reported adverse events. Four RCTs with 247 participants (methotrexate = 128 and cyclosporine = 119) were included. Pooled analysis showed no significant difference in PASI 75 (risk ratio [RR] = 0.81; 95% confidence interval [CI]: 0.56-1.18; <i>P</i> = .27; <i>I</i>² = 80%) and PASI 90 (RR = 1.03; 95% CI: 0.50-2.11; <i>P</i> = .94; <i>I</i>² = 65%) between methotrexate and cyclosporine. Reduction at 4, 8, and 12 weeks (mean difference = -1.15 [95% CI: -0.23 to 2.53]; <i>P</i> = .10) showed no difference between the 2 treatments, but the difference was not statistically significant. In terms of safety, methotrexate had fewer adverse events overall but was more associated with elevated liver enzymes (RR = 13.35). Methotrexate and cyclosporine show comparable efficacy in moderate-to-severe psoriasis, though methotrexate has a more favorable safety profile.