Weekly vs. daily administration of oral methotrexate (MTX) for generalized plaque psoriasis: a randomized controlled clinical trial

Abstract Methotrexate (MTX) treatment for psoriasis is most often administered weekly, because the drug has been considered more hepatotoxic when taken daily. However, some patients may tolerate smaller, more frequent doses better. Objective To study the efficacy and toxicity of daily vs. weekly MTX. Patients and methods In a randomized controlled trial, 101 patients with generalized plaque psoriasis received oral MTX 2.5 mg daily for 6 days (Group 1), and another 101 patients received oral MTX 15 mg weekly (Group 2) in three divided doses (every 8 hours during a 24‐hour period). Patients were followed monthly for 4 months as research participants, then for 1 year as part of their routine care. Complete blood counts, liver function tests, blood urea nitrogen, serum creatinine, urinalysis, and psoriasis area and severity index (PASI) scores were determined pre‐treatment and at the following intervals after starting treatment: 2 weeks, 4 weeks and monthly for a total of 4 months. Changes in PASI scores were classified into three categories: >75% improvement was considered significant; 25–75% moderate; and <25% poor. Results Sixty Group 1 patients and 81 Group 2 patients showed a significant response ( P ‐value 0.001); 19 patients in Group 1 and 14 in Group 2 responded moderately; 22 patients in Group 1 and six patients from Group 2 responded poorly. Forty‐five patients in Group 1 and 33 in Group 2 developed transient increases in liver enzymes ( P ‐value 0.11). Nausea, headache, fatigue, and gastrointestinal upset were noted in four Group 1 patients and 30 Group 2 patients ( P ‐value 0.0001). Conclusion Nausea, vomiting, headache, and fatigue were significantly less common side effects in our patients who received MTX daily, but liver enzyme abnormalities were less common, and clinical efficacy was greater in the patients who received MTX weekly.