Atopic dermatitis and skin disease
Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: A systematic review

https://doi.org/10.1016/j.jaci.2013.07.049Get rights and content

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.

Section snippets

Methods

We conducted a systematic review on the efficacy and safety of immunomodulating systemic treatments (further noted as “systemics”) for moderate-to-severe AD.

Results of the literature search

Of the 925 references retrieved by using the systematic search, 34 RCTs11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 were selected for review, including a total of 1653 patients (see Fig E1 in this article's Online Repository at www.jacionline.org).

Study characteristics

Twelve different types of systemic treatments for moderate-to-severe AD were investigated.

Fourteen RCTs evaluated CsA.

Discussion

This systematic review provides an evidence-based treatment algorithm for patients with moderate-to-severe AD. By ranking the quality of evidence based on the GRADE approach45 and by taking into account the efficacy and safety shown for short-term (and long-term) use and the number of participants, this review extends previous research and guidelines in which less specific treatment recommendations were made based on expert opinion46 or less systematic approaches, such as the Goodman method47

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  • Cited by (0)

    Disclosure of potential conflict of interest: P. I. Spuls is the coauthor of the MACAD trial included in this review, has consultant arrangements for Novartis, and is the principal investigator of the Department for Clinical Trials with Pharma. J. Schmitt has consultant arrangements with Novartis and has grants/grants pending with Novartis, Abbott, MSD, and Wyeth. The rest of the authors declare that they have no relevant conflicts of interest.

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