title: Teduglutide, a novel mucosally active analog of glucagon-like peptide-2 (GLP-2) for the treatment of moderate to severe Crohn's disease.
abstract: BACKGROUND
  Teduglutide, an analog of glucagon-like peptide-2 (GLP-2), is associated with trophic effects on gut mucosa. Its role in the treatment of active Crohn's disease (CD) was assessed in a pilot, randomized, placebo-controlled, double-blinded, dose-ranging study.
  
  
  METHODS
  Subjects with moderate-to-severe CD were randomized 1:1:1:1 to placebo or 1 of 3 doses of teduglutide (0.05, 0.10, or 0.20 mg/kg daily) delivered as a daily subcutaneous injection for 8 weeks. The primary outcome measure was the percentage of subjects in each group that responded to treatment, defined as a decrease in Crohn's Disease Activity Index (CDAI) score to <150 or a decrease of > 100 points. At week 8 there was an optional 12-week open-label period of treatment with teduglutide 0.10 mg/kg/d.
  
  
  RESULTS
  One hundred subjects were enrolled and 71 completed the study. The mean baseline CDAI score was 290.8 +/- 57.6 and was similar across groups. There were numerically higher response and remission rates in all teduglutide-treated groups as compared with placebo, although the percentage of subjects who achieved a clinical response or remission was more substantial, and seen as early as week 2 of treatment in the highest dose (0.2 mg/kg/d) group (44% response and 32% remission versus 32% response and 20% remission in the placebo group). Of subjects who had not achieved remission during the 8-week placebo-controlled phase in the higher-dose group, 50% achieved remission during the more prolonged, open-label treatment phase. Plasma citrulline was similar across groups at baseline, but increased substantially over time in all teduglutide groups when compared with placebo at week 8. Adverse events were not different between placebo and active treatment groups.
  
  
  CONCLUSIONS
  Teduglutide is a novel and potentially effective therapy for inducing remission and mucosal healing in patients with active moderate-to-severe CD. Further clinical investigation of this growth factor is warranted.
authors.affiliation: Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. a-buchman@northwestern.edu
authors.forename: Alan L
authors.initials: AL
authors.lastname: Buchman
authors.forename: Seymour
authors.initials: S
authors.lastname: Katz
authors.forename: John C
authors.initials: JC
authors.lastname: Fang
authors.forename: Charles N
authors.initials: CN
authors.lastname: Bernstein
authors.forename: Souheil G
authors.initials: SG
authors.lastname: Abou-Assi
mesh_terms: D000293:Adolescent; D000328:Adult; D002956:Citrulline / Q000097:blood; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D053767:Glucagon-Like Peptide 2 / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; D053767:Glucagon-Like Peptide 2; D010455:Peptides; D002956:Citrulline; C494910:teduglutide