title: Combined use of systemic agents for psoriasis: a systematic review.
abstract: OBJECTIVE
  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.
  
  
  OBJECTIVE
  To summarize and critically appraise the evidence on efficacy and safety of combination therapy with systemic agents in plaque-type psoriasis.
  
  
  METHODS
  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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Celine
authors.initials: C
authors.lastname: Busard
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Zweegers
authors.affiliation: Medical Library, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Limpens
authors.affiliation: Dutch Cochrane Centre, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Miranda
authors.initials: M
authors.lastname: Langendam
authors.affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Phyllis I
authors.initials: PI
authors.lastname: Spuls
mesh_terms: D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D003879:Dermatologic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept; D008727:Methotrexate