title: Secukinumab in plaque psoriasis--results of two phase 3 trials.
abstract: BACKGROUND
  Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis.
  
  
  METHODS
  In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points).
  
  
  RESULTS
  The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators). The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept.
  
  
  CONCLUSIONS
  Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.).
authors.affiliation: From Dalhousie University, Halifax, NS (R.G.L.), Clinical Research (K.P.) and Probity Medical Research (K.P., L.S.), Waterloo, ON, and Stratica Medical and Probity Medical Research, Edmonton, AB (N.W.) - all in Canada; University of Alabama, Birmingham (B.E.E.); Mount Sinai Hospital, New York (M.L.); Dermatologikum Hamburg and Georg-August-Universität, Göttingen, Germany (K.R.); Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom (C.E.M.G.); Hospital de Sant Pau, Barcelona (L.P.); Jikei University School of Medicine, Tokyo (H.N.); Veracity Clinical Research, Woolloongabba, QLD, Australia (L.S.); Faculty of Medicine, Department of Dermatology, University of Iceland, Reykjavik (B.S.); Dermos, Guatemala City, Guatemala (E.R.); Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei (T.-F.T.); University of Texas Health Science Center and Center for Clinical Studies, Houston (S.T.); and Novartis Pharma, Basel, Switzerland (T.S., I.H., M.N., A.K., S.H., C.P.).
authors.forename: Richard G
authors.initials: RG
authors.lastname: Langley
authors.forename: Boni E
authors.initials: BE
authors.lastname: Elewski
authors.forename: Mark
authors.initials: M
authors.lastname: Lebwohl
authors.forename: Kristian
authors.initials: K
authors.lastname: Reich
authors.forename: Christopher E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: Kim
authors.initials: K
authors.lastname: Papp
authors.forename: Lluís
authors.initials: L
authors.lastname: Puig
authors.forename: Hidemi
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Lynda
authors.initials: L
authors.lastname: Spelman
authors.forename: Bárður
authors.initials: B
authors.lastname: Sigurgeirsson
authors.forename: Enrique
authors.initials: E
authors.lastname: Rivas
authors.forename: Tsen-Fang
authors.initials: TF
authors.lastname: Tsai
authors.forename: Norman
authors.initials: N
authors.lastname: Wasel
authors.forename: Stephen
authors.initials: S
authors.lastname: Tyring
authors.forename: Thomas
authors.initials: T
authors.lastname: Salko
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hampele
authors.forename: Marianne
authors.initials: M
authors.lastname: Notter
authors.forename: Alexander
authors.initials: A
authors.lastname: Karpov
authors.forename: Silvia
authors.initials: S
authors.lastname: Helou
authors.forename: Charis
authors.initials: C
authors.lastname: Papavassilis
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D000068800:Etanercept; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007239:Infections / Q000209:etiology; D007279:Injections, Subcutaneous; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C508717:IL17A protein, human; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D018124:Receptors, Tumor Necrosis Factor; C555450:secukinumab; D000068800:Etanercept