title: Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study.
abstract: BACKGROUND
  Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients, and although current biologic treatments are generally well tolerated, concerns exist with respect to long-term safety. Interleukin (IL)-17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells, a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity.
  
  
  OBJECTIVE
  To assess the efficacy and safety of different doses of secukinumab, a fully human anti-IL-17A IgG1κ monoclonal antibody, in patients with moderate-to-severe plaque psoriasis.
  
  
  METHODS
  Patients (n = 125) were randomized 1 : 1 : 1 : 1 : 1 to receive subcutaneous doses of placebo (n = 22) or secukinumab [1 × 25 mg (n = 29), 3 × 25 mg (n = 26), 3 × 75 mg (n = 21) or 3 × 150 mg (n = 27)] at weeks 0, 4 and 8. After the 12-week treatment period, patients entered a follow-up period of 24 weeks. The primary efficacy outcome was at least 75% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 75); secondary outcomes included the Investigator's Global Assessment (IGA) and PASI 90 and 50 response rates.
  
  
  RESULTS
  After 12 weeks of treatment, secukinumab 3 × 150 mg and 3 × 75 mg resulted in significantly higher PASI 75 response rates vs. placebo (82% and 57% vs. 9%; P < 0·001 and P = 0·002, respectively). Higher PASI 75 response rates compared with placebo were maintained throughout the follow-up period with these dosages [week 36, 26% (n = 7) and 19% (n = 4) vs. 4% (n = 1), respectively], with a gradual decline of PASI 75 response over time after the dosing period. IGA response rates were significantly higher in the 3 × 150 mg group vs. placebo at week 12 (48% vs. 9%; P = 0·005) and were consistently higher for the 3 × 150 mg and 3 × 75 mg groups vs. placebo at all time points from week 4 onward. The PASI 90 response rate was significantly higher in the 3 × 150 mg group vs. placebo (52% vs. 5%) at week 12 and remained higher during the follow-up period. Secukinumab was well tolerated. Two cases of neutropenia (≤ grade 2) were reported in the 3 × 150 mg cohort.
  
  
  CONCLUSIONS
  Treatment with subcutaneous secukinumab 3 × 75 mg and 3 × 150 mg met the primary outcome of PASI 75 response achievement after 12 weeks, demonstrating efficacy in moderate-to-severe psoriasis.
authors.affiliation: Probity Medical Research, 135 Union Street East, Waterloo, ON N2J 1C4, Canada. kapapp@probitymedical.com
authors.forename: K A
authors.initials: KA
authors.lastname: Papp
authors.forename: R G
authors.initials: RG
authors.lastname: Langley
authors.forename: B
authors.initials: B
authors.lastname: Sigurgeirsson
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: D R
authors.initials: DR
authors.lastname: Baker
authors.forename: P
authors.initials: P
authors.lastname: Konno
authors.forename: S
authors.initials: S
authors.lastname: Haemmerle
authors.forename: H J
authors.initials: HJ
authors.lastname: Thurston
authors.forename: C
authors.initials: C
authors.lastname: Papavassilis
authors.forename: H B
authors.initials: HB
authors.lastname: Richards
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D001835:Body Weight; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003879:Dermatologic Agents; C555450:secukinumab