title: Fontolizumab in moderate to severe Crohn's disease: a phase 2, randomized, double-blind, placebo-controlled, multiple-dose study.
abstract: BACKGROUND
  The safety and efficacy of fontolizumab, a humanized anti-interferon gamma antibody, was investigated in patients with Crohn's disease (CD). Elevated gut mucosal levels of interferon gamma, a key cytokine involved in the inflammatory process of CD, are associated with disease symptoms.
  
  
  METHODS
  A total of 201 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450 were randomized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo, followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks. Clinical response at day 29, the primary efficacy endpoint, was defined as a decrease in the CDAI of at least 100 points from baseline levels.
  
  
  RESULTS
  Of 201 patients, 135 (67%) completed the study. Day 29 response rates were similar in all treatment groups (31%-38%). At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo. All fontolizumab groups had significant improvement in C-reactive protein levels. The overall frequency of adverse events was similar in all groups (58%-75%); most events were related to exacerbation of CD. There was a low frequency (5.2%) of neutralizing antibodies to fontolizumab.
  
  
  CONCLUSIONS
  Although a strong clinical response to fontolizumab was not observed, significant decreases in C-reactive protein levels suggest a biological effect. Fontolizumab was well tolerated, and further studies to assess its efficacy are warranted.
authors.affiliation: Clinic of Internal Medicine III, Department of Gastroenterology and Hepatology, University of Vienna, Vienna, Austria. walter.reinisch@meduniwien.ac.at
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.forename: Williem
authors.initials: W
authors.lastname: de Villiers
authors.forename: László
authors.initials: L
authors.lastname: Bene
authors.forename: László
authors.initials: L
authors.lastname: Simon
authors.forename: István
authors.initials: I
authors.lastname: Rácz
authors.forename: Seymour
authors.initials: S
authors.lastname: Katz
authors.forename: István
authors.initials: I
authors.lastname: Altorjay
authors.forename: Brian
authors.initials: B
authors.lastname: Feagan
authors.forename: Dennis
authors.initials: D
authors.lastname: Riff
authors.forename: Charles N
authors.initials: CN
authors.lastname: Bernstein
authors.forename: Daniel
authors.initials: D
authors.lastname: Hommes
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: Antoine
authors.initials: A
authors.lastname: Cortot
authors.forename: Michael
authors.initials: M
authors.lastname: Gaspari
authors.forename: May
authors.initials: M
authors.lastname: Cheng
authors.forename: Tillman
authors.initials: T
authors.lastname: Pearce
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D055104:Infusions, Subcutaneous; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005765:Gastrointestinal Agents; C505731:fontolizumab