Modest Efficacy for Methotrexate in Psoriasis Save

Doubt remains regarding the appropriateness, efficacy and safety of methotrexate in the treatment of moderate to severe cutaneous psoriasis. Moreover, high dose, subcutaneous methotrexate has not been studied in a well-designed trial.

The METOP study was a 52-week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial performed in 120 European patients with chronic, moderate to severe plaque psoriasis who were methotrexate (MTX)-naive.

Patients were predominantly Caucasian, with a mean PASI score of 15 and BSA of 20%. They were randomized to either MTX 17·5 mg/week subcutaneously or placebo for the first 16 weeks, followed by MTX for up to 52 weeks. Dose escalation to 22·5 mg/week was allowed after 8 weeks for those not achieving a PASI 50% response.Treatment was combined with folic acid 5 mg/week.

At week 16, a PASI 75 response was achieved in 41% of those on MTX (compare to a 10% PBO response (p=0·0026).

Subcutaneous MTX was generally well tolerated; no patients died or had serious infections, malignancies, or major adverse cardiovascular events. Hepatic enzyme elevation was seen in 13% of MTX and 7% of PBO patients. Serious adverse events were seen only three (3%) patients on MTX.

These results strongly indicate the safety and efficacy of subcutaneous methotrexate in patients with psoriasis. 

An editorial by Dr. Dafna Gladman points out these results affirm the findings of earlier investigations showing the efficacy of MTX in psoriasis.  Yet she points out that these ~40% PASI75 results are inferior to many current biologic therapies (60-80% responses).  She notes the value of the current study but stresses the need for longer-term studies, comparative studies, that will address skin, systemic and comorbid outcomes as well.