Efficacy and safety of systemic methotrexate in two fixed doses of 10 mg or 25 mg orally once weekly in adult patients with severe plaque-type psoriasis: a prospective, randomized, double-blind, dose-ranging study

BACKGROUND: Methotrexate (MTX) is the 'gold-standard' drug for the treatment of severe psoriasis. In the absence of any consensus on an optimum dose of MTX for psoriasis, there is wide variation in prescribing patterns between dermatologists, resulting in variable or delayed therapeutic effects. AIM: To identify the most effective fixed single weekly dose of oral MTX with acceptable side-effects in the treatment of severe plaque-type psoriasis. METHODS: This was a prospective, randomized, double-blind, parallel-group, dose-ranging study, which enrolled 60 patients of both genders (aged 18-62 years) with severe chronic plaque-type psoriasis. Patients were randomly assigned to one of two groups: group A was treated with MTX 10 mg once weekly, and group B was treated with 25 mg MTX once weekly. The main outcome measure was change in Psoriasis Area and Severity Index (PASI) between the two groups from baseline to 12 weeks. RESULTS: Of the 60 patients, 51 (85%) completed the 12-week study. At the end of the study, 24 patients (92.3%) in the MTX 25 mg group had achieved a 75% reduction in PASI (PASI 75) from baseline, compared with 18 patients (72%) in the MTX 10 mg group (P>0.05). Mean time in weeks to achieve PASI 75 was significantly shorter in the MTX 25mg group (7.92±1.91) than in the MTX 10mg group (9.47±2.29) (P<0.05). In addition, 20 patients (69%) in the MTX 25mg group achieved 100% reduction in PASI compared with 9 patients (30%) in the MTX 10mg group within 12weeks of the study period (P<0.01). Adverse effects were generally mild, and were noted in 43.1% of the 51 patients who completed the study, with no significant difference in frequency between the two groups, although they were less severe in the 10mg group. CONCLUSIONS: MTX 25mg is an effective dose as monotherapy for the treatment of severe psoriasis, whereas the 10mg dose is slow to act and less effective, but has a less severe side-effect profile.