title: Treatment of active Crohn's disease with MLN0002, a humanized antibody to the alpha4beta7 integrin.
abstract: OBJECTIVE
  Selective blockade of lymphocyte-vascular endothelium interactions in the gastrointestinal tract is a promising therapeutic strategy for inflammatory bowel disease. This randomized, double-blind, controlled trial assessed the efficacy and safety of MLN0002, a monoclonal antibody targeting the alpha4beta7 integrin, in patients with active Crohn's disease.
  
  
  METHODS
  Patients were randomized to receive MLN0002 2.0 mg/kg (n = 65), MLN0002 0.5 mg/kg (n = 62), or placebo (n = 58) by intravenous infusion on days 1 and 29. The primary efficacy end point was clinical response (>or=70-point decrement in the Crohn's Disease Activity Index [CDAI] score) on day 57. Secondary end points were the proportions of patients with clinical remission (CDAI score <or=150) and with an enhanced clinical response (>or=100-point decrement in CDAI). Human anti-human antibody levels were measured.
  
  
  RESULTS
  Clinical response rates at day 57 were 53%, 49%, and 41% in the MLN0002 2.0 mg/kg, MLN0002 0.5 mg/kg, and placebo groups. Clinical remission rates at day 57 were 37%, 30%, and 21%, respectively (P = .04 for the 2.0 mg/kg vs placebo comparison). At day 57, 12% and 34% of patients in the 2.0- and 0.5-mg/kg groups had clinically significant human anti-human antibody levels (titers > 1:125). There was one infusion-related hypersensitivity reaction. The most common serious adverse event was worsening of Crohn's disease.
  
  
  CONCLUSIONS
  This phase 2 study was suggestive of a dose-dependent beneficial effect of MLN0002 therapy on clinical remission. MLN0002 was well tolerated in patients with active Crohn's disease.
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, London, Ontario, Canada. bfeagan@robarts.ca
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Greenberg
authors.forename: Gary
authors.initials: G
authors.lastname: Wild
authors.forename: Richard N
authors.initials: RN
authors.lastname: Fedorak
authors.forename: Pierre
authors.initials: P
authors.lastname: Paré
authors.forename: John W D
authors.initials: JW
authors.lastname: McDonald
authors.forename: Albert
authors.initials: A
authors.lastname: Cohen
authors.forename: Alain
authors.initials: A
authors.lastname: Bitton
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Baker
authors.forename: Réjean
authors.initials: R
authors.lastname: Dubé
authors.forename: Steven B
authors.initials: SB
authors.lastname: Landau
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Vandervoort
authors.forename: Asit
authors.initials: A
authors.lastname: Parikh
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D016023:Integrins / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016023:Integrins; D010919:Placebos; C071777:integrin alpha4beta7; C543529:vedolizumab