title: Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3).
abstract: BACKGROUND
  Patients with psoriasis who have an inadequate response to one biologic may benefit from switching to a new biologic, such as ixekizumab, a high affinity monoclonal antibody that selectively targets interleukin (IL)-17A.
  
  
  OBJECTIVE
  Our aim was to assess the response to ixekizumab in patients with moderate-to-severe plaque psoriasis who did not respond adequately to etanercept using a post-hoc analysis in two phase III studies.
  
  
  METHODS
  For the subanalyses in two phase III trials (UNCOVER-2 and -3), non-response was defined by either failure to have a static physician global assessment (sPGA) of 0/1 in UNCOVER-2 or failure to have at least 75% improvement in psoriasis area and severity index (PASI 75) in UNCOVER-3 at Week 12 of each study. Non-responders treated with twice-weekly etanercept 50 mg in the first 12 weeks received two injections of placebo at Week 12 (4-week wash-out period), followed by ixekizumab every 4 weeks (Q4W) for Weeks 16-60. Non-responders to placebo in the first 12 weeks were administered ixekizumab 160 mg at Week 12, followed by ixekizumab Q4W for Weeks 16-60.
  
  
  RESULTS
  After switching to ixekizumab Q4W, a substantial proportion of patients with moderate-to-severe psoriasis who did not respond to etanercept experienced rapid and durable improvement in all efficacy evaluations. Among sPGA 0/1 (UNCOVER-2) and PASI 75 (UNCOVER-3) non-responders to etanercept, 73.0% achieved sPGA 0/1 and 78.2% achieved PASI 75, respectively, after 12 weeks of ixekizumab treatment. Safety profiles in patients switched from etanercept to ixekizumab were similar to those in patients switched from placebo to ixekizumab.
  
  
  CONCLUSIONS
  Patients who were non-responders to etanercept after 12 weeks, as defined by failure to meet sPGA 0/1 (UNCOVER-2) or PASI 75 (UNCOVER-3), achieved high levels of response 12 weeks after switching to ixekizumab. Studies are registered with ClinicalTrials.gov (NCT01597245 and NCT01646177).
authors.affiliation: Oregon Medical Research Center, 9495 SW Locust St., Suite G, Portland, OR, 97223, USA. ablauvelt@oregonmedicalresearch.com.
authors.forename: Andrew
authors.initials: A
authors.lastname: Blauvelt
authors.affiliation: K Papp Clinical Research and Probity Medical Research, Waterloo, Canada.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Papp
authors.affiliation: Dermatology Centre, Salford Royal Hospital, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
authors.forename: Christopher E M
authors.initials: CEM
authors.lastname: Griffiths
authors.affiliation: Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Puig
authors.affiliation: Medical Dermatology Specialists, Inc., Atlanta, GA, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Weisman
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Yves
authors.initials: Y
authors.lastname: Dutronc
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Lisa Farmer
authors.initials: LF
authors.lastname: Kerr
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Dapo
authors.initials: D
authors.lastname: Ilo
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Lotus
authors.initials: L
authors.lastname: Mallbris
authors.affiliation: Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Augustin
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D057915:Drug Substitution; D000068800:Etanercept / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D012720:Severity of Illness Index; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D061067:Antibodies, Monoclonal, Humanized; C508717:IL17A protein, human; D020381:Interleukin-17; C549079:ixekizumab; D000068800:Etanercept