title: Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Evelien
authors.initials: E
authors.lastname: Roekevisch
authors.affiliation: Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Phyllis Ira
authors.initials: PI
authors.lastname: Spuls
authors.affiliation: Centre for Evidence-based Healthcare, University Hospital Dresden, Dresden, Germany; Institute for Occupational and Social Medicine, Technical University Dresden, Dresden, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Kuester
authors.affiliation: Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Limpens
authors.affiliation: Centre for Evidence-based Healthcare, University Hospital Dresden, Dresden, Germany; Institute for Occupational and Social Medicine, Technical University Dresden, Dresden, Germany. Electronic address: jochen.schmitt@uniklinikum-dresden.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schmitt
mesh_terms: D001379:Azathioprine / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine; D008727:Methotrexate
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