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

J Allergy Clin Immunol. 2014 Feb;133(2):429-38. doi: 10.1016/j.jaci.2013.07.049. Epub 2013 Oct 24.


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.

Keywords: AD; AE; AZA; Adverse event; Atopic dermatitis; Azathioprine; CsA; Cyclosporin A; EASI; EC-MPS; Eczema Area and Severity Index; Enteric-coated mycophenolate sodium; GRADE; Grading of Recommendations Assessment, Development and Evaluation; IVIG; Intravenous immunoglobulin; MTX; Methotrexate; RCT; Randomized controlled trial; SAE; Serious adverse event; TCHM; TP-5; Thymopentin; Traditional Chinese herbal medicine; evidence-based medicine/systematic review; immunomodulator; immunosuppressive therapy; recommendations; systemic treatment.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Azathioprine / therapeutic use
  • Cyclosporine / therapeutic use
  • Dermatitis, Atopic / drug therapy*
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-gamma / therapeutic use
  • Methotrexate / therapeutic use
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use


  • Glucocorticoids
  • Immunosuppressive Agents
  • Interferon-gamma
  • Cyclosporine
  • Mycophenolic Acid
  • Azathioprine
  • Methotrexate