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

Abstract

Eluxadoline, a peripherally acting, mixed µ- and κ-opioid receptor (OR) agonist and δ-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. To evaluate eluxadoline's efficacy on altered bowel functions and safety in IBS-D patients with or without BAD. 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, 100mg tablets BID, with food for 4weeks. Patients recorded bowel functions by electronic daily diary. BAD was based on fasting serum 7αC4 (> 52.5ng/mL) or concurrent criteria of increased total or primary fecal BAs excreted in 48h. 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. Mean changes from baseline in cohorts 1 and 2 (data presented in this order) were similar for: BSFS score averaged over 4weeks' 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 7αC4 (-5.59 and -8.78ng/mL). There were no deaths, serious treatment-emergent adverse events, or discontinuations due to adverse events during the study. 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.