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Evidence-Based Dermatology
November 2014

Combined Use of Systemic Agents for Psoriasis: A Systematic Review

Author Affiliations
  • 1Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
  • 2Department of Dermatology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
  • 3Medical Library, Academic Medical Center, Amsterdam, the Netherlands
  • 4Dutch Cochrane Centre, Academic Medical Center, Amsterdam, the Netherlands
JAMA Dermatol. 2014;150(11):1213-1220. doi:10.1001/jamadermatol.2014.1111

Importance  Combined use of systemic agents may be necessary to achieve disease control in therapy-resistant patients. However, to our knowledge, an overview of evidence, including quality assessments, is not yet available, and no guidance on monitoring, contraindications, and interactions exists.

Objectives  To summarize and critically appraise the evidence on efficacy and safety of combination therapy with systemic agents in plaque-type psoriasis.

Evidence Review  Through March 2013, an electronic search limited to randomized clinical trials was performed in MEDLINE, EMBASE, The Cochrane Library, and ongoing trial registers. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach.

Findings  The initial search retrieved 2583 records, of which 17 met the inclusion criteria. Most studies favored combination therapy, albeit with low significance and low quality of evidence. Etanercept plus methotrexate was the only combination therapy investigated with an adequate sample size (n = 478). In the short term, this combination had superior efficacy with a moderate quality of evidence compared with etanercept monotherapy (Psoriasis Area and Severity Index, 75; relative risk, 1.28; 95% CI, 1.14-1.45). Although this finding coincided with an increase in adverse events (relative risk, 1.25; 95% CI, 1.10-1.42), the overall safety profile remained acceptable.

Conclusions and Relevance  This systematic review provides a comprehensive overview on the validity of different systemic combination therapies. For most combinations, insufficient evidence is available. Initial results indicate that combined therapy with etanercept plus methotrexate may be beneficial in patients that are therapy resistant under intensive follow-up. Dose reductions should be taken into account to minimize adverse effects.

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