Introduction Eluxadoline (ELX) is a mixed µ- and κ-opioid receptor (OR) agonist and δ-OR antagonist. It is locally active and approved for the treatment of IBS-D. The effectiveness of ELX was evaluated in clinically relevant subgroups from pooled data from Phase 3 clinical trials.
Methods Two double-blind, placebo (PBO)-controlled, Phase 3 clinical trials (IBS-3001 and IBS-3002) randomised patients meeting Rome III criteria for IBS-D to twice-daily treatment with ELX (75 or 100 mg) or PBO. Patients rated IBS symptoms daily including worst abdominal pain (WAP; 0–10 scale) and stool consistency (Bristol Stool Scale). The primary endpoint was composite response (based on simultaneous daily improvement in WAP and stool consistency with ≥50% of days demonstrating a response) evaluated over Weeks 1–12. Subgroup analyses were conducted on the pooled ITT population with comparisons based on a Cochran–Mantel–Haenszel analysis. Subgroups aincluded those based on gender, histories of gastroesophageal reflux disease (GERD) and depression, and prior cholecystectomy status. The impact of baseline IBS pain severity (<5, 5– <8, and ≥8) was examined with a stratified analysis.
Results 2423 patients with IBS-D were included. The majority of patients were female (66%) and had baseline WAP scores of 5– <8. Histories of GERD and depression were reported for 31% and 25% of patients, respectively, and 20% of patients had a prior cholecystectomy. In males and females, significantly more patients (p ≤ 0.002) receiving ELX 75 and 100 mg were composite responders than patients receiving PBO (Table). Additionally, significantly greater responder proportions were seen with ELX treatment among patients with histories of GERD (75 and 100 mg) and depression (100 mg), or among patients with a prior cholecystectomy (75 and 100 mg) [Table]. When stratified by baseline WAP, responder proportions were significantly higher for both eluxadoline groups (p < 0.001) vs. placebo.
Conclusion Overall, treatment with ELX is effective in both male and female patients with IBS-D and multiple relevant subgroup populations based on composite response.
Reference 1 Previously presented at ACG 2015. Abstract #1760, Am J Gastroenterol 2015;110:S739–S766. doi:10.1038/ajg.2015.275.
Disclosure of Interest B. Lacy Consultant for: Ironwood, Takeda, Salix, Allergan plc, Covidien, W. Chey Grant/research support from: Ironwood, Nestle, Prometheus, Vibrant, Perrigo, Consultant for: Allergan plc, Ardelyx, Asubio, AstraZeneca, Ironwood, Nestle, Prometheus, Salix/Valeant, Sucampo, Takeda, Conflict with: My GI Health, My Nutrition Health, Digital Monometry, My Total Health, A. Lembo Consultant for: Allergan plc, L. Dove Consultant for: Allergan plc, P. Covington: None Declared
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