Drug use and toxicity in psoriatic disease: Focus on methotrexate

Methotrexate (MTX) toxicity in psoriatic disease was the focus of discussion at the 2007 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Plenary presentations and results of a Web-based opinion survey of rheumatologists and dermatologists from GRAPPA, and others from New Zealand, Australia, and Canada, provided topics of discussion for small-group breakout sessions, including hepatotoxicity, alcohol use, fertility and pregnancy, and combination therapy. As a framework, topics were considered under headings: importance, knowledge deficit, sufficient data for a recommendation, and research agenda. Breakout session conclusions/consensus were as follows: (1) Data are insufficient to recommend routine serial liver biopsy to prevent MTX-induced liver fibrosis; further research is needed to establish whether serial liver chemistry tests or propeptide of type III collagen can detect hepatotoxicity without the need for liver biopsy. (2) Insufficient data are available to establish a dose-response relationship between alcohol use and MTX hepatotoxicity, so no safe limit of alcohol intake can be recommended. (3) Although cessation of MTX 3 months prior to conception is reasonable, inadequate data are available to specify duration or to quantify the risk of adverse fetal outcome; registries to track pregnancy outcome are potentially useful. (4) Combination therapy with anti-TNF agents or sulfasalazine is safe, but insufficient data are available for combinations with leflunomide or cyclosporine.