Abstract
Background: Patients with irritable bowel syndrome with diarrhea (IBS-D) experience a range of abdominal and bowel symptoms; successful management requires alleviation of this constellation of symptoms. Eluxadoline, a locally active mixed μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist, is approved for the treatment of IBS-D in adults based on the results of 2 Phase 3 studies. Radar plots can facilitate comprehensive, visual evaluation of diverse but interrelated efficacy endpoints. Methods: Two double-blind, placebo-controlled, Phase 3 trials (IBS-3001 and IBS-3002) randomized patients meeting Rome III criteria for IBS-D to twice-daily eluxadoline 75 or 100 mg or placebo. Radar plots were prepared showing pooled Weeks 1-26 response rates for the primary efficacy composite endpoint (simultaneous improvement in abdominal pain and stool consistency), stool consistency, abdominal pain, urgency-free days, and adequate relief, and change from baseline to Week 26 in IBS-D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and daily number of bowel movements. Key Results: The studies enrolled 2428 patients. Eluxadoline increased Weeks 1-26 responder proportions vs placebo for the composite endpoint, stool consistency, abdominal pain, urgency-free days, and adequate relief. Changes from baseline to Week 26 in IBS-D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and number of bowel movements were greater with eluxadoline vs placebo. Conclusions and Inferences: Data presentation in radar plot format facilitates interpretation across multiple domains, demonstrating that eluxadoline treatment led to improvements vs placebo across 13 endpoints representing the range of symptoms experienced by patients with IBS-D.
Original language | English (US) |
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Article number | e13331 |
Journal | Neurogastroenterology and Motility |
Volume | 30 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2018 |
Funding
The authors received no compensation related to the development of the manuscript. Financial arrangements of the authors with companies whose products may be related to the present report are listed below, as declared by the authors. Darren M. Brenner has served as a consultant, advisor, and speaker for Allergan plc, AstraZeneca, Daiichi Sankyo, the GI Health Foundation, Ironwood Pharmaceuticals, Inc., Medscape LLC, Salix Pharmaceuticals/ValeantPharmaceuticals,andSynergyPharmaceuticals. Leonard S. Dove serves as a scientific consultant to Allergan plc. David A. Andrae is a former employee of Allergan plc. Paul S. Covington has acted as a scientific consultant for Actavis, Inc., an affiliate of Allergan plc. Catherine Gutman is an employee of Allergan plc and has received company stock options as part of compensation. William D. Chey has received grant support from Ironwood Pharmaceuticals, Inc., Nestlé, and Prometheus Laboratories; has served as an advisor or consultant for Allergan plc, Biomerica, IM Health, Ironwood Pharmaceuticals, Inc., Nestlé, Proctor & Gamble Pharmaceuticals, Prometheus Laboratories, QOL Medical, Ritter, and Salix Pharmaceuticals; and has served as a speaker for the GI Health Foundation. Funding information These studies were funded by Allergan plc. The authors had complete access to the data that support the studies. The authors thank Helen Woodroof, PhD, of Complete HealthVizion, for editorial assistance in the writing and revision of the draft manuscript on the basis of detailed discussion and feedback from all the authors; this assistance was funded by Allergan plc.
Keywords
- abdominal pain
- diarrhea
- eluxadoline
- irritable bowel syndrome
- radar plots
ASJC Scopus subject areas
- Endocrine and Autonomic Systems
- Gastroenterology
- Physiology