Teduglutide, a novel mucosally active analog of glucagon-like peptide-2 (GLP-2)
for the treatment of moderate to severe Crohn's disease.
Author(s): Buchman AL(1), Katz S, Fang JC, Bernstein CN, Abou-Assi SG; Teduglutide Study
Group.
Collaborators: Ertan A, Fang J, Wo J, Bassan I, Goff J, Lashner B, Katz S,
Prakash J, Hanauer S, Krone C, Lebovitz P, Buchman A, Abou-Assi S, Ziegler T,
Hamilton J, Saucego J, Loewe C, Oranglo G, Anderson F, Bernstein C, Cohen L,
Leddin D, Weiss LM, Zwick A, Kornbluth A, Petrunia D, Dhana S, Barish C, Chiba N,
Liebermann T, Hogin J, Cortese F.
Affiliation(s): Author information:
(1)Division of Gastroenterology, Feinberg School of Medicine, Northwestern
University, Chicago, Illinois 60611, USA. a-buchman@northwestern.edu
Publication date & source: 2010, Inflamm Bowel Dis. , 16(6):962-73
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.
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