title: Continuous dosing versus interrupted therapy with ixekizumab: an integrated analysis of two phase 3 trials in psoriasis.
abstract: BACKGROUND
  Continuous treatment is recommended for patients with moderate-to-severe psoriasis; however, treatment may need to be interrupted in routine clinical practice.
  
  
  OBJECTIVE
  To assess outcomes in patients continuously treated with ixekizumab versus those who interrupted therapy and were subsequently retreated with ixekizumab (IXE).
  
  
  METHODS
  This analysis used data pooled from two phase 3 trials, UNCOVER-1 and UNCOVER-2. Patients were randomized to placebo (PBO), IXE every 4 (Q4W) or IXE every 2 weeks (Q2W) for 12 weeks. Patients with a static Physician's Global Assessment (sPGA) 0, 1 at Week 12 were rerandomized to IXEQ4W, IXE every 12 weeks (not presented) or PBO. We examined outcomes in patients who were continuously treated (IXEQ2W/IXEQ4W; IXEQ4W/IXEQ4W) or withdrawn (IXEQ2W/PBO; IXEQ4W/PBO), and in patients who were withdrawn and retreated with IXEQ4W for 24 weeks after disease relapse (sPGA ≥3).
  
  
  RESULTS
  A total of 1226 treated patients achieved an sPGA 0, 1 at Week 12 and entered the maintenance phase; of these patients, 402 and 416 were rerandomized to PBO and IXEQ4W, respectively. Among patients interrupting treatment, 157 (82.2%) of IXEQ4W/PBO and 176 (83.4%) of IXEQ2W/PBO had an sPGA ≥3 by Week 60; median time to relapse was approximately 20 weeks irrespective of induction dose. At Week 60, continuously treated patients maintained high levels of PASI and sPGA responses (90.0% PASI 75 IXEQ2W/IXEQ4W; 81.9% sPGA 0, 1 IXEQ2W/IXEQ4W, non-responder imputation). After 24 weeks of retreatment with IXEQ4W (IXEQ2W/PBO/IXEQ4W and IXEQ4W/PBO/IXEQ4W), 87.0% (107 of 123) and 95.1% (97 of 102) (observed), respectively, of patients recaptured PASI 75 and 70.7% (104 of 147) and 82.3% (107 of 130) (observed) recaptured an sPGA 0, 1. Overall, adverse events in continuously treated and retreated patients were comparable.
  
  
  CONCLUSIONS
  High levels of response were sustained with continuous ixekizumab treatment through 60 weeks. Most patients who were withdrawn experienced disease relapse, and most of those patients recaptured response after 24 weeks of retreatment.
authors.affiliation: Oregon Medical Research Center, Portland, OR, USA.
authors.forename: A
authors.initials: A
authors.lastname: Blauvelt
authors.affiliation: Probity Medical Research and K. Papp Clinical Research, Waterloo, ON, Canada.
authors.forename: K A
authors.initials: KA
authors.lastname: Papp
authors.affiliation: Department of Medicine (Dermatology), David Geffen School of Medicine, Los Angeles, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sofen
authors.affiliation: Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Augustin
authors.affiliation: Department of Dermatology, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: G
authors.initials: G
authors.lastname: Yosipovitch
authors.affiliation: Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Katoh
authors.affiliation: Psoriasis-Center, Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Mrowietz
authors.affiliation: Department of Dermatology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohtsuki
authors.affiliation: Department of Medicine, Université Laval, Hôpital Hôtel-Dieu de Québec, Quebec, QC, Canada.|Centre de Recherche Dermatologique du Québec Métropolitain, Quebec, QC, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Poulin
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: D
authors.initials: D
authors.lastname: Shrom
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: R
authors.initials: R
authors.lastname: Burge
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: K
authors.initials: K
authors.lastname: See
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: L
authors.initials: L
authors.lastname: Mallbris
authors.affiliation: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Gordon
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D010919:Placebos; D011565:Psoriasis / Q000188:drug therapy*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D010919:Placebos; C549079:ixekizumab