Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review.

BACKGROUND: Many patients with moderate-to-severe atopic dermatitis (AD) require systemic immunomodulating treatment to achieve adequate disease control. OBJECTIVE: We sought to systematically evaluate the efficacy and safety of systemic treatments for moderate-to-severe AD. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, and CENTRAL (until June 2012). Randomized controlled trials (RCTs) evaluating systemic immunomodulating treatments for moderate-to-severe AD were included. Selection, data extraction, quality assessment, and generation of treatment recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach were performed independently by 2 reviewers. Efficacy outcomes were clinical signs, symptoms, quality of life, and the course of AD. Safety data were compared by calculating the weekly incidence rates (as percentages) for adverse events. RESULTS: Thirty-four RCTs with 12 different systemic treatments and totaling 1653 patients were included. Fourteen trials consistently indicate that cyclosporin A efficaciously improves clinical signs of AD. Cyclosporin A is recommended as first-line treatment for short-term use. A second-line treatment option is azathioprine, but efficacy is lower, and evidence is weaker. Methotrexate can be considered a third-line treatment option. Recommendations are impossible for mycophenolate, montelukast, intravenous immunoglobulins, and systemic glucocorticosteroids because of limited evidence. A meta-analysis was not performed because of a lack of standardization in outcome measures. CONCLUSION: Although 12 different interventions for moderate-to-severe AD have been studied in 34 RCTs, strong recommendations are only possible for the short-term use of cyclosporin A. Methodological limitations in the majority of trials prevent evidence-based conclusions. Large head-to-head trials evaluating long-term treatments are required.

A randomized trial of methotrexate versus azathioprine for severe atopic eczema.

BACKGROUND: Patients with severe atopic eczema frequently require systemic treatment to control their disease. Methotrexate and azathioprine are proposed as off-label treatment options, but direct comparisons are lacking. OBJECTIVES: We sought to compare the efficacy and safety of methotrexate versus azathioprine in adults with severe atopic eczema. METHODS: Patients with severe atopic eczema were randomly assigned in a 1:1 ratio to receive either methotrexate (dosage, 10-22.5 mg/wk) or azathioprine (dosage, 1.5-2.5 mg/kg/d) for 12 weeks, followed by a 12-week follow-up period. Primary outcome was the mean change in the severity scoring of atopic dermatitis index after 12 weeks. Efficacy assessors blinded for allocation of treatment were used to perform clinical outcome assessment. Analyses were done on an intention-to-treat basis. RESULTS: Of the 45 patients screened, 42 were included. At week 12, patients in the methotrexate group had a mean relative reduction in the severity scoring of atopic dermatitis index of 42% (SD, 18%) compared with 39% (SD, 25%) in the azathioprine group (P = .52). Proportions of patients achieving at least mild disease and reductions on impact of quality of life, symptoms, and levels of thymus and activation-regulated chemokine 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. No serious adverse events occurred. CONCLUSION: Both treatments achieved clinically relevant improvement and were safe in the short term. Methotrexate and azathioprine are appropriate options for the treatment of severe atopic eczema.