Safety and Efficacy of Eluxadoline in Patients with Irritable Bowel Syndrome-Diarrhea With or Without Bile Acid Diarrhea: Open-Label Study

Background Eluxadoline, a peripherally acting, mixed mu- and kappa-opioid receptor (OR) agonist and delta-OR antagonist, is approved for treatment of adults with irritable bowel syndrome-diarrhea (IBS-D). About a third of IBS-D patients has bile acid diarrhea (BAD); opioids may stimulate TGR5 (bile acid) receptors. Aim To evaluate eluxadoline's efficacy on altered bowel functions and safety in IBS-D patients with or without BAD. Methods In a single-center, phase 4, parallel-group, open-label study, patients with IBS-D (cohort 1) and patients with BAD were treated with eluxadoline, 100 mg tablets BID, with food for 4 weeks. Patients recorded bowel functions by electronic daily diary. BAD was based on fasting serum 7 alpha C4 (> 52.5 ng/mL) or concurrent criteria of increased total or primary fecal BAs excreted in 48 h. We assessed efficacy on treatment compared to baseline in the two cohorts. Primary outcome measures were changes from baseline in average stool consistency Bristol Stool Form Scale (BSFS) score (range 1-7) and safety. Results Mean changes from baseline in cohorts 1 and 2 (data presented in this order) were similar for: BSFS score averaged over 4 weeks' treatment (- 1.25 and - 1.09); daily bowel movement frequency (- 1.48 and - 0.79); daily urgent bowel movements (- 0.52 and - 0.80); IBS-QoL (5.9 and 13.6); serum 7 alpha C4 (- 5.59 and - 8.78 ng/mL). There were no deaths, serious treatment-emergent adverse events, or discontinuations due to adverse events during the study. Conclusion Eluxadoline is similarly efficacious in the treatment of IBS-D and BAD, and it appears to be safe and efficacious as documented in large clinical trials.