AIM: Schram et al. aimed to compare the efficacy and safety of methotrexate vs. azathioprine in adults with severe atopic eczema. SETTING AND DESIGN: This single-blind, parallel-group (ratio 1 : 1), randomized controlled trial was conducted in a secondary care setting in the Netherlands between July 2009 and December 2010. STUDY EXPOSURE:  Patients with severe atopic eczema were randomly assigned in a 1 : 1 ratio to receive either methotrexate (10-22·5 mg weekly) or azathioprine (1·5-2·5 mg kg(-1) daily) for 12 weeks, followed by a 12-week follow-up period. OUTCOMES: The outcome measures comprised various eczema severity measures including: SCORing of Atopic Dermatitis index (SCORAD); Investigator Global Assessment (IGA); Patient Global Assessment (PGA); Eczema Area and Severity Index (EASI); and Patient-Oriented Eczema Measurement (POEM). Further outcomes included a visual analogue scale of itch and sleeplessness; Skindex-17; serum levels of thymus and activation-regulated chemokine; quantity of topical corticosteroids used; and the number of courses of rescue medication (oral prednisolone) used. PRIMARY OUTCOME MEASURE:   The primary outcome was the mean change in SCORAD after 12 weeks of treatment. RESULTS: Forty-five patients were screened and 42 of these were included in the trial. At week 12, patients in the methotrexate group had a mean ± SD relative reduction in SCORAD of 42 ± 18% compared with 39 ± 25% in the azathioprine group (P = 0·52). Proportions of patients achieving at least mild disease and reductions in impact on quality of life and symptoms were similar in both groups at weeks 12 and 24. No statistically significant differences were found in the number and severity of adverse events. Abnormalities in blood count were more common in the azathioprine group but no serious adverse events occurred in either group. CONCLUSIONS: Schram et al. conclude that both methotrexate and azathioprine achieved clinically relevant improvement and were safe in the short term. They also conclude that both treatments are appropriate treatment options for severe atopic eczema in adult populations.