An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

In RCT (n=120), subjects received methotrexate (MTX) 17.5 mg/week or placebo for 1st 16 weeks, followed by MTX for all patients up to 52 weeks. At week 16, a PASI 75 response was achieved in 37 (41%) patients on MTX vs. 3 (10%) on placebo (RR 3.93, 95% CI 1.31–11.81; p=0.0026).

In the study, dose escalation to 22.5 mg/week was allowed after 8 weeks of methotrexate treatment if patients had not achieved at least a 50% reduction in baseline Psoriasis Area and Severity Index score (PASI).

 

The researchers note that to the best of their knowledge, this is the first double-blind, randomised, placebo-controlled study of an intensified two-step dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis. They suggest that their findings indicate methotrexate can be started at a higher dose with no detrimental effect on risk, and that a subcutaneous formulation and dosing scheme could lead to a more rapid and sustained response than that typically seen with oral regimens.

 

According to a commentary, the question that remains is whether methotrexate should remain the first-line systemic therapy for moderate to severe psoriasis. It notes that this study provides information about high-dose subcutaneous methotrexate, but only in the short term; long-term follow-up would provide information about sustainability and maintenance of disease control, and prevention of comorbidities.