title: Secukinumab retreatment-as-needed versus fixed-interval maintenance regimen for moderate to severe plaque psoriasis: A randomized, double-blind, noninferiority trial (SCULPTURE).
abstract: BACKGROUND
  Secukinumab has demonstrated high, sustained efficacy in psoriasis to 52 weeks on a fixed-interval regimen.
  
  
  OBJECTIVE
  We sought to compare a retreatment-as-needed versus a fixed-interval regimen.
  
  
  METHODS
  In this double-blind study, adults with moderate to severe plaque psoriasis were randomized 1:1 to subcutaneous secukinumab at 300 mg (n = 484) or 150 mg (n = 482) weekly from baseline until week 4, and at week 8. At week 12, patients achieving 75% or more improvement from baseline Psoriasis Area and Severity Index score (PASI 75) were rerandomized to 2 dose levels of secukinumab retreatment as needed (n = 217, 300 mg; n = 206, 150 mg) or fixed interval (n = 217; n = 203). Primary end point was noninferiority of retreatment as needed versus fixed interval for maintaining PASI 75 to week 52.
  
  
  RESULTS
  Secukinumab induced high responses by week 12 (84.4%-91.1% PASI 75 responders). From week 12 to week 52, more patients on fixed interval (78.2%, 300 mg; 62.1%, 150 mg) maintained PASI 75 versus retreatment as needed (67.7%; 52.4%); statistical noninferiority of retreatment as needed was not established. Overall safety, including very low incidences of treatment-emergent anti-drug antibodies (<0.5%), was similar between regimens.
  
  
  CONCLUSIONS
  The primary end point was developed without any known precedent.
  
  
  CONCLUSIONS
  Secukinumab fixed interval showed clear benefit versus the study-specified retreatment-as-needed regimen for maintaining efficacy. Both regimens exhibited safety consistent with previous trials. The potential of retreatment as needed with secukinumab warrants further investigation.
authors.affiliation: Psoriasis Center, Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. Electronic address: umrowietz@dermatology.uni-kiel.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mrowietz
authors.affiliation: Saint Louis University School of Medicine, St Louis, Missouri.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Leonardi
authors.affiliation: Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Girolomoni
authors.affiliation: XLR8 Medical Research, Windsor, Ontario, Canada.
authors.forename: Darryl
authors.initials: D
authors.lastname: Toth
authors.affiliation: Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Akimichi
authors.initials: A
authors.lastname: Morita
authors.affiliation: Shree Hospital and Critical Care Center, Nagpur, India.
authors.forename: Shyamal A
authors.initials: SA
authors.lastname: Balki
authors.affiliation: Department of Dermatology, Venereology, and Allergology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Jacek C
authors.initials: JC
authors.lastname: Szepietowski
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Regnault
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Helen
authors.initials: H
authors.lastname: Thurston
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Charis
authors.initials: C
authors.lastname: Papavassilis
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D019233:Retreatment; D012720:Severity of Illness Index
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C555450:secukinumab
keywords: clinical trial; dosing; immunogenicity; noninferiority; psoriasis; retreatment as needed; secukinumab