Comparative efficacy and safety of oral versus subcutaneous methotrexate in the treatment of psoriasis: a systematic review, pairwise and network meta-analysis with CINeMA and GRADE assessment.

backgroundMethotrexate (MTX) is a cornerstone of systemic therapy for treating moderate to severe psoriasis. It can be given orally or subcutaneously (SC). SC MTX offers higher bioavailability and more predictable exposure. However, head-to-head clinical evidence is limited. We systematically compared the efficacy and safety of SC and oral MTX to inform route selection.

methodsBuilding upon this background, we conducted a systematic review and network meta-analysis with random effects. Randomized controlled trials (RCTs) were identified from major databases up to 2025. Ten RCTs met the inclusion criteria. Outcomes included change in Psoriasis Area and Severity Index (PASI) from baseline, PASI 50/75/90/100 responses, and adverse events. Treatments were ranked using the Surface Under the Cumulative Ranking curve (SUCRA) probabilities.

resultsOur review and analysis showed that, across analyses, subcutaneous methotrexate (SC MTX) ranked higher than oral methotrexate (oral MTX) for PASI75 (SUCRA 0.98 vs. 0.52), PASI90 (0.98 vs. 0.39), and PASI100 (0.93 vs. 0.50). Subcutaneous methotrexate increased the odds of PASI75 (OR 5.48, 95% CI 2.53-11.85) and PASI90 (OR 3.33, 95% CI 1.09-10.13). Oral methotrexate slightly favored PASI50. Neither formulation reached significance for PASI100. Mean PASI reduction did not differ directly, despite superior rankings for subcutaneous methotrexate. Subcutaneous methotrexate was also associated with fewer adverse events and lower rates of discontinuation.

conclusionSC MTX more effectively achieves PASI thresholds and is better tolerated, supporting its use as the preferred systemic treatment for moderate to severe psoriasis.