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Methotrexate (MTX) is the antimetabolite most often prescribed by dermatologists for moderate-to-severe psoriasis. Hepatotoxicity is the primary clinical concern when planning long-term methotrexate therapy. Mild transaminase elevations (less than twice the upper limit of normal) are to be expected during therapy, but these levels do not correlate with hepatic fibrosis. A 2009 consensus conference advocates following the American College of Rheumatology guidelines for patients with no risk factors for liver injury and recommend considering liver biopsy or switching to another treatment after to 4 g to total cumulative methotrexate dosage. Folic acid (FA) supplementation at 1 mg daily is recommended to abate the gastrointestinal side effects of methotrexate without reducing efficacy (although many providers hold FA on the day of MTX therapy). It also helps to prevent megaloblastic anemia.

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