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. Inflamm Bowel Dis 2009
1Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
2Long Island Jewish Hospital, New Hyde Park, New York
3Division of Gastroenterology, University of Utah, Salt Lake City, Utah
4Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada
5Medical College of Virginia, Richmond, Virginia
*Reprints: Director, IBD Center, Medical Director, Intestinal Rehabilitation and Transplant Center Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, 676 N. St. Clair St., Suite 1400, Chicago, IL 60611
Received for publication 17 August 2009; Accepted 19 August 2009.
Published online 9 October 2009 in Wiley InterScience (www.interscience.wiley.com).
Grant sponsor: NPS Pharmaceuticals, Bedminster, NJ.
List of participating investigators and centers: Ertan, Atilla (Houston, TX); Fang, John (University of Utah), Wo, John (University of Louisville); Bassan, Issac (North Miami Beach, FL); Goff, John (Lakewood, CO); Lashner, Brett (Cleveland Clinic); Katz, Seymour (Great Neck, NY); Prakash, Jay (Atlanta, GA); Hanauer, Stephen (University of Chicago); Krone, Charles (Tucson, AZ); Lebovitz, Paul (Pittsburgh); Buchman, Alan (Northwestern University, Chicago); Abou‐Assi, Sounen (McGuire VAMC, Richmond, VA); Ziegler, Thomas (Emory University, Atlanta); Hamilton, John (Madison, WI); Saucego, Juno (Washington DC); Loewe, Charles (Sarasota, FL); Oranglo, Guy (Atlanta, GA); Anderson, Frank (Vancouver, BC); Bernstein, Charles (Univ of Manitoba, Winnepeg); Cohen Lawrence (Toronto, ON); Leddin, Desmond (Halifax, NS); Weiss, L Michael (Clearwater, FL); Zwick, Andrew (Boca Raton, FL); Kornbluth, Asher (Mt. Sinai Hospital, New York); Petrunia, Dennis (Victoria, BC); Dhana, Sonny (Brandon, MD); Barish, Charles (Raleigh, NC); Chiba, Naoki (Guelph, ON); Liebermann, Thomas (Austin, TX); Hogin James (Oklahoma, OK); Cortese, Florian (Butte, MT).