Subcutaneous methotrexate in patients with moderate to severe psoriasis: a critical appraisal

Summary

Aim

Warren et al¹ set out to assess the effect of an intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe chronic plaque psoriasis.

Setting and design

This is a prospective, double-blind, randomised (3:1), placebo-controlled study, conducted across 16 centres in Germany, France, the Netherlands, and the UK.

Study exposure

Methotrexate-naïve adults with a diagnosis of moderate to severe chronic plaque psoriasis for at least 6 months before baseline were randomly assigned to receive weekly subcutaneous injections of either methotrexate at a starting dose of 17.5 mg, or placebo for 16 weeks (first phase).Dose escalation to 22.5 mg/week was implemented after 8 weeks if patients did not achieve PASI 50. Treatment was combined with folic acid 5 mg/week. The first phase of the study was followed by an open-label period from 16-52 weeks (second phase), in which both groups received weekly methotrexate injections. At week 24, dose escalation to 22.5 mg/week was possible in patients not achieving PASI 50.

Outcomes

Psoriasis severity was measured using the PASI (Psoriasis Area and Severity Index). The authors also used two other psoriasis severity measures and two quality of life measures, looked at safety indices and performed a sub-study analysing paired skin biopsies at baseline and week 16 (histopathology, immunohistochemistry and expression of interleukin (IL)17A, interferon-γ and tumour necrosis factor-α).

Primary outcome measures

The primary outcome was the proportion of patients reaching PASI 75 at week 16.

Results

120 patients were included in this trial, most of whom were middle-aged white men with longstanding psoriasis and a mean BMI of 30.1 kg/m². PASI 75 was achieved in 41% of patients receiving methotrexate vs. 10% of patients receiving placebo (RR 3.93, 95% CI 1.31–11.81; p=0.0026) at week 16. Subcutaneous methotrexate was generally well tolerated, with no serious adverse events related to this treatment over the 52-week study.

Conclusions

Warren et al conclude that the 52-week risk-benefit profile of subcutaneous methotrexate is favourable in patients with psoriasis.

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