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Identifying a subpopulation with higher likelihoods of early response to treatment in a heterogeneous rare disease: a post hoc study of response to teduglutide for short bowel syndrome

Authors Chen KS, Xie J, Tang W, Zhao J, Jeppesen PB, Signorovitch JE

Received 21 February 2018

Accepted for publication 20 May 2018

Published 25 July 2018 Volume 2018:14 Pages 1267—1277

DOI https://doi.org/10.2147/TCRM.S166081

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Professor Garry Walsh


Kristina S Chen,1 Jipan Xie,2 Wenxi Tang,3 Jing Zhao,4 Palle B Jeppesen,5 James E Signorovitch4

1Outcomes Research and Epidemiology, Shire Human Genetic Therapies, Inc., Cambridge, MA, USA; 2Analysis Group, Inc., Los Angeles, CA, USA; 3Analysis Group, Inc., New York, NY, USA; 4Analysis Group, Inc., Boston, MA, USA; 5Department of Medical Gastroenterology, Rigshospitalet, Copenhagen, Denmark

Purpose: Teduglutide, a glucagon-like peptide-2 analog, has demonstrated efficacy in reducing parenteral support (PS) among patients with short bowel syndrome with intestinal failure (SBS–IF). This study aims to identify a subpopulation of SBS–IF patients for whom teduglutide has an especially pronounced effect.
Patients and methods: Data were from a 24-week, Phase III trial (Study of Teduglutide Effectiveness in Parenteral Nutrition-Dependent SBS Subjects; NCT00798967) that randomized SBS–IF patients with PS dependency to receive teduglutide (n=43) or placebo (n=43). Two prediction models (1 for each arm) were developed for response, defined as 20% reduction in weekly PS at Weeks 20 and 24. Potential predictors included demographics, disease characteristics, and concomitant medications. Patients were then ranked based on the effect score, an individualized predicted response rate difference with teduglutide versus placebo. A subpopulation of patients with a pronounced benefit from teduglutide versus placebo was identified. Baseline characteristics and clinical outcomes were compared between patients included versus those not included in the subpopulation.
Results: Six predictors of response to teduglutide were selected: older age, volvulus as the cause of major intestinal resection, baseline PS volume >6 L per week, longer time since start of PS dependency, absence of ileocecal valve, and lower percentage of colon remaining. Higher percentage of colon remaining and volvulus were the selected predictors for response to placebo. A subpopulation of patients more likely to respond to teduglutide was identified as those with the top 60% effect scores. The difference in response rate between teduglutide and placebo was 62% in the subpopulation, which was substantially higher than the difference of 33% in the overall population. Mean PS day reduction was also significantly higher for teduglutide compared to placebo in the subpopulation.
Conclusion: Pretreatment characteristics as predictors of response to teduglutide versus placebo within 24 weeks were identifiable in the clinical trial population of SBS–IF patients.

Keywords: SBS, intestinal failure, teduglutide, subpopulation

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