title: Briakinumab for treatment of Crohn's disease: results of a randomized trial.
abstract: BACKGROUND
  This study assessed the efficacy and safety of briakinumab, a human anti-IL-12/23p40 monoclonal antibody, compared with placebo for the induction and maintenance of remission in patients with moderately to severely active Crohn's disease.
  
  
  METHODS
  In this phase 2b, multicenter, double-blind, parallel group study, 246 patients stratified by prior tumor necrosis factor-antagonist use and response, were randomized (1:1:1:3) to 4 intravenous induction regimens: placebo, 200, 400, or 700 mg briakinumab, at weeks 0/4/8. At week 12, responders in the placebo or 400-mg induction groups entered the maintenance phase with the same regimen, whereas responders in the 700-mg induction group were rerandomized (1:1:1) to receive placebo, 200, or 700 mg briakinumab at weeks 12/16/20. At week 24, patients in remission stopped receiving study drug (withdrawal phase) until relapse. Patients experiencing relapse, nonresponders, and nonremitters could enter the open-label phase.
  
  
  RESULTS
  The primary end point of clinical remission at week 6 was not met. There were numerically greater rates of remission and response at 6, 12, or 24 weeks in patients treated with briakinumab. The safety and tolerability profile of briakinumab was similar in the induction and maintenance phases of the trial.
  
  
  CONCLUSIONS
  Briakinumab showed a similar safety and tolerability profile to placebo in the induction and maintenance phases, and comparable rates of serious adverse events, adverse events leading to discontinuation, and malignancy. These data provide support for the potential efficacy of briakinumab and other IL-12/23 inhibitors in the treatment of moderate-to-severe Crohn's disease.
authors.affiliation: *Inflammatory Bowel Disease Unit, Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, AB, Canada; †Division of Gastroenterology, University of California San Diego, La Jolla, California; ‡Center for Digestive and Liver Diseases, Inc., Mexico, Missouri; §Division of Gastroenterology, School of Medicine, University of Washington Medical Center, Seattle, Washington; ‖Consultants for Clinical Research, Cincinnati, Ohio; ¶Gastroenterology Associates of Central Georgia, Macon, Georgia; **Robarts Research Institute, University of Western Ontario, London, ON, Canada; ††University of Chicago, Chicago, Illinois; ‡‡Department of Medicine, McMaster University, Hamilton, ON, Canada; §§Inflammatory Bowel Disease Program, Gastroenterology, Hepatology and Nutrition, University of Utah, Salt Lake City, Utah; ‖‖Data and Statistical Sciences, AbbVie Inc., North Chicago, Illinois; and ¶¶Therapeutic Area Immunology, Pharmaceutical Development, AbbVie GmbH & Co. KG, Ludwigshafen, Germany.
authors.forename: Remo
authors.initials: R
authors.lastname: Panaccione
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: Glenn L
authors.initials: GL
authors.lastname: Gordon
authors.forename: Scott D
authors.initials: SD
authors.lastname: Lee
authors.forename: Alan
authors.initials: A
authors.lastname: Safdi
authors.forename: Shahriar
authors.initials: S
authors.lastname: Sedghi
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanauer
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.forename: John F
authors.initials: JF
authors.lastname: Valentine
authors.forename: Bidan
authors.initials: B
authors.lastname: Huang
authors.forename: Roberto
authors.initials: R
authors.lastname: Carcereri
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053762:Interleukin-12 Subunit p40; D014409:Tumor Necrosis Factor-alpha; C544528:briakinumab