title: Off-label biologic regimens in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy.
abstract: OBJECTIVE
  While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment) with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment.
  
  
  METHODS
  We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospective clinical trials that studied biologic therapy for psoriasis treatment in adults. Individual articles were screened for studies that examined escalated, reduced, or interrupted therapy with etanercept, adalimumab, infliximab, ustekinumab, or alefacept.
  
  
  RESULTS
  A total of 23 articles with 12,617 patients matched the inclusion and exclusion criteria for the systematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non-responders, dose escalation with etanercept, adalimumab, ustekinumab, and alefacept typically resulted in greater efficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial response rates for most biologics. Safety data on off-label dosing regimens are limited.
  
  
  CONCLUSIONS
  Dose escalation in non-responders generally resulted in increased efficacy in the examined biologics used to treat moderate-to-severe psoriasis. Continuous treatment with anti-TNF agents and anti-IL12/23 agent results in superior efficacy over interrupted therapy. The decision to use off-label dosing needs to account for both benefits and risks and be individualized to patients' disease severity, quality of life, and existence of comorbidities.
authors.affiliation: School of Medicine, University of California Davis, Sacramento, California, United States of America.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Brezinski
authors.forename: April W
authors.initials: AW
authors.lastname: Armstrong
mesh_terms: D017277:Drug Approval; D054796:Drug Dosage Calculations; D006801:Humans; D056687:Off-Label Use / Q000331:legislation & jurisprudence / Q000706:statistics & numerical data*; D011565:Psoriasis / Q000188:drug therapy*; D012449:Safety; D028761:Withholding Treatment / Q000706:statistics & numerical data*