title: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Brodalumab in Patients With Moderate-to-Severe Crohn's Disease.
abstract: OBJECTIVE
  To assess the safety and efficacy of brodalumab, a human anti-interleukin-17 receptor monoclonal antibody, in patients with moderate-to-severe Crohn's disease (CD).
  
  
  METHODS
  Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study in patients with moderate-to-severe CD and evidence of active inflammation. Patients were randomized 1:1:1:1 to receive brodalumab (210, 350, or 700 mg at baseline and week 4) or placebo. The primary end point was proportion of patients achieving Crohn's disease activity index (CDAI) remission (≤150) at week 6. Secondary end points included proportion of patients with CDAI response (reduction from baseline of ≥100) at week 6 and change from baseline in CDAI at week 6.
  
  
  RESULTS
  The study was terminated early based on an imbalance in worsening CD in active treatment groups. At the time of termination, 130 patients had been randomized. At week 6, remission rates were 3% (210 mg), 15% (350 mg), 9% (700 mg), and 3% (placebo) and CDAI response occurred in 16% (210 mg), 27% (350 mg), 15% (700 mg), and 13% (placebo) of patients. Mean change in CDAI at week 6 was -8.7 (95.3) (210 mg), -35.4 (105.6) (350 mg), -0.6 (105.9) (700 mg), and -28.2 (86.0) (placebo). Besides worsening of CD, overall incidences of adverse events were similar across treatment groups.
  
  
  CONCLUSIONS
  Treatment with brodalumab resulted in a disproportionate number of cases of worsening CD in patients with active CD and no evidence of meaningful efficacy. These analyses did not suggest additional safety risks of brodalumab beyond worsening of CD symptoms in patients with active CD.
authors.affiliation: Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
authors.affiliation: Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Feagan
authors.affiliation: Department of Gastroenterology, University Hospitals KU Leuven, Leuven, Belgium.
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: University of Calgary, Calgary, Alberta, Canada.
authors.forename: Remo
authors.initials: R
authors.lastname: Panaccione
authors.affiliation: Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Gil Y
authors.initials: GY
authors.lastname: Melmed
authors.affiliation: Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Landers
authors.affiliation: Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Dalin
authors.initials: D
authors.lastname: Li
authors.affiliation: Amgen, Thousand Oaks, California, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Russell
authors.affiliation: Amgen, Thousand Oaks, California, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Newmark
authors.affiliation: Amgen, Thousand Oaks, California, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Amgen, Thousand Oaks, California, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chon
authors.affiliation: Amgen, Thousand Oaks, California, USA.
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Amgen, Thousand Oaks, California, USA.
authors.forename: Shao-Lee
authors.initials: SL
authors.lastname: Lin
authors.affiliation: Amgen, Thousand Oaks, California, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Klekotka
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053722:Receptors, Interleukin-17 / Q000037:antagonists & inhibitors; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C109985:IL17RA protein, human; D053722:Receptors, Interleukin-17; C571216:brodalumab