PUTTING PAPERS INTO PRACTICE BJD British Journal of Dermatology A randomized trial of methotrexate vs. azathioprine for severe atopic eczema: a critical appraisal DOI: 10.1111/j.1365-2133.2012.10872.x ORIGINAL ARTICLE: Schram ME, Roekevisch E, Leeflang MMG, Bos JD, Schmitt J, Spuls PI. A randomized trial of methotrexate versus azathioprine for severe atopic eczema. J Allergy Clin Immunol 2011; 128: 353–9 Summary 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 metho- trexate (10–22Æ5 mg weekly) or azathioprine (1Æ5– 2Æ5 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 =0Æ52). 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. Comment What is already known about this topic? Eczema is a common chronic inflammatory skin disorder that affects both child and adult populations. There is a need for novel, medium to long term treatment options for patients with severe eczema. 1 Although effective, ciclosporin and pred- nisolone are best used as short-term treatments, the former being nephrotoxic and the latter predisposing to osteoporosis, hypertension and other side-effects. 2 As healthcare costs increase, dermatologists are keen to know which treatments achieve disease control safely and with minimum cost. 1 Methotrexate and azathioprine are both low-cost steroid- sparing systemic agents that are used to treat eczema, but both are unlicensed for this indication. There is a paucity of evi- dence for the use of methotrexate in eczema. No randomized controlled trial (RCT) of methotrexate in eczema exists and the only published evidence for its efficacy consists of case series and open-label studies. 3–6 There is more evidence to support the use of azathioprine to treat eczema, although the only two published RCTs of azathioprine in eczema were pla- cebo controlled. 7,8 Uncontrolled studies on azathioprine also exist, showing similar results. An RCT comparing metho- trexate and azathioprine in eczema has not been previously performed. Schram et al. 1 are to be congratulated for undertak- ing the first study comparing azathioprine and methotrexate in eczema. Strengths of research This study is the first head-to-head comparison of methotrex- ate against azathioprine in patients with severe atopic eczema. This study was not industry sponsored and the investigators had no relevant conflict of interest, making biased interpreta- tion of results less likely. The study is well reported, closely following the CONSORT guidelines for reporting of RCTs. 9 Markers of good reporting in this study include: clearly stated primary and secondary outcome measures; the use of a table showing the baseline characteristics of participants in each group and a flow diagram to show the fate of participants who entered the study; full reporting of side-effects; registra- tion of the study on the Dutch Trials Register; and a thorough Ó 2012 The Authors BJD Ó 2012 British Association of Dermatologists 2012 166, pp701–707 701