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.