title: A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis.
abstract: BACKGROUND
  The interleukin-17 cytokine family plays a central role in psoriasis pathogenesis.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of brodalumab, a human anti-interleukin-17 receptor antibody, in treating patients with moderate-to-severe plaque psoriasis.
  
  
  METHODS
  In this phase III, double-blind, placebo-controlled study (NCT01708590; AMAGINE-1), adult patients in the U.S.A., Canada and Europe were randomized to brodalumab (140 or 210 mg) or placebo every 2 weeks (Q2W), with an additional dose at week 1, for a 12-week induction phase. At week 12, patients receiving brodalumab who achieved static Physician's Global Assessment 0 or 1 (sPGA success) were rerandomized to the placebo or induction dose. After week 16, patients with sPGA ≥ 3 were re-treated with the induction dose. After ≥ 12 weeks of retreatment, patients with sPGA 2 for ≥ 4 weeks or sPGA ≥ 3 were rescued with brodalumab 210 mg Q2W. At week 12, patients randomized to brodalumab with sPGA ≥ 2 or placebo received brodalumab 210 mg Q2W. Coprimary end points were the percentage of patients with ≥ 75% improvement in Psoriasis Area and Severity Index score (PASI 75) and sPGA success at week 12.
  
  
  RESULTS
  There were 661 patients randomized: 220 placebo, 219 brodalumab 140 mg and 222 brodalumab 210 mg. At week 12, 60% (140 mg) and 83% (210 mg) vs. 3% (placebo) achieved PASI 75, and 54% (140 mg) and 76% (210 mg) vs. 1% (placebo) achieved sPGA success. The safety profile was considered acceptable.
  
  
  CONCLUSIONS
  Brodalumab therapy resulted in significant clinical benefit and an acceptable safety profile in patients with moderate-to-severe plaque psoriasis.
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: Dermatologikum Hamburg and SCIderm Research Institute, Hamburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Reich
authors.affiliation: Paul Sabatier University, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Paul
authors.affiliation: Oregon Medical Research Center, Portland, OR, U.S.A.
authors.forename: A
authors.initials: A
authors.lastname: Blauvelt
authors.affiliation: Wroclaw Medical University, Wroclaw, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Baran
authors.affiliation: The University of Montreal and Innovaderm Research, Montreal, QC, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Bolduc
authors.affiliation: XLR8 Medical Research and Probity Medical Research, Windsor, ON, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Toth
authors.affiliation: Dalhousie University, Halifax, NS, Canada.
authors.forename: R G
authors.initials: RG
authors.lastname: Langley
authors.affiliation: Modern Research Associates, Modern Dermatology, A Baylor Health Texas Affiliate, and Probity Medical Research, Dallas, TX, U.S.A.
authors.forename: J
authors.initials: J
authors.lastname: Cather
authors.affiliation: Tufts Medical Center, Boston, MA, U.S.A.
authors.forename: A B
authors.initials: AB
authors.lastname: Gottlieb
authors.affiliation: University of Lübeck, Lübeck, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Thaçi
authors.affiliation: The Rockefeller University, New York, NY, U.S.A.
authors.forename: J G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Amgen Inc., Thousand Oaks, CA, U.S.A.
authors.forename: C B
authors.initials: CB
authors.lastname: Russell
authors.affiliation: Amgen Inc., Thousand Oaks, CA, U.S.A.
authors.forename: C E
authors.initials: CE
authors.lastname: Milmont
authors.affiliation: Amgen Inc., Thousand Oaks, CA, U.S.A.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Amgen Inc., Thousand Oaks, CA, U.S.A.
authors.forename: P A
authors.initials: PA
authors.lastname: Klekotka
authors.affiliation: Amgen Inc., Thousand Oaks, CA, U.S.A.
authors.forename: G
authors.initials: G
authors.lastname: Kricorian
authors.affiliation: Amgen Inc., Thousand Oaks, CA, U.S.A.
authors.forename: A
authors.initials: A
authors.lastname: Nirula
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D001008:Anxiety Disorders / Q000517:prevention & control; D015415:Biomarkers / Q000378:metabolism; D003866:Depressive Disorder / Q000517:prevention & control; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D057915:Drug Substitution; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D011565:Psoriasis / Q000188:drug therapy* / Q000523:psychology; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D003879:Dermatologic Agents; C571216:brodalumab