Eluxadoline appears to be a safe and effective treatment for the symptoms of irritable bowel syndrome with diarrhea (IBS-D) in patients with intact gallbladders who have previously reported inadequate relief with loperamide, according to a study published in The American Journal of Gastroenterology.
The functional gastrointestinal disorder IBS-D has limited effective treatment options. The typical initial therapeutic interventions include dietary and lifestyle modifications, along with over-the-counter antidiarrheals.
This prospective, multicenter, placebo-controlled, double-blind, multinational phase 4 study assessed the safety and efficacy of eluxadoline in adult patients (N=346) with IBS-D who experienced inadequate control of symptoms with loperamide. Participants were randomly assigned to 100 mg of eluxadoline twice daily (n=172) or placebo (n=174) for 12 weeks, during which time they recorded daily symptoms, including consistency of stool according to the Bristol Stool Scale and worst abdominal pain (WAP). Primary efficacy endpoint was proportion of composite responders, which was defined as participants meeting the daily composite response criteria (≥40% WAP improvement in the preceding 24 hours and <5 Bristol Stool Scale score) for >50% of treatment days, and recorded ≥60 days of diary entries over the 12-week period.
During the 12-week study, a statistically significantly greater proportion of participants taking eluxadoline achieved the primary composite endpoint compared with participants taking placebo (22.7% vs 10.3%; P =.002), as well as the component endpoints of improvements in WAP (43.6% vs 31.0%, P =.02) and stool consistency (27.9% vs 16.7%, P =.01). Furthermore, a greater proportion of participants taking eluxadoline met the primary composite endpoint as assessed at monthly intervals compared with participants taking placebo (weeks 1-4: 14.0% vs 6.9%, P =.03; weeks 5-8: 26.7% vs 14.9%, P =.006; weeks 9-12: 30.8% vs 16.7%, P =.002). No serious treatment-related adverse events, cases of pancreatitis, or of sphincter of Oddi spasm were reported, and adverse events rates were comparable between groups (37.4% vs 35.3%).
Study investigators concluded that, “results of the current study demonstrate positive treatment beneﬁts for eluxadoline over placebo in patients with IBS-D reporting inadequate symptom relief from loperamide, based on improvements in both abdominal pain and stool consistency, the cardinal symptoms of IBS. Moreover, the safety proﬁle of eluxadoline was comparable to placebo, with no new safety concerns identiﬁed. We conclude that this study prospectively validates previous ﬁndings revealing eluxadoline to be a safe, eﬀective IBS-D treatment in patients reporting inadequate symptom relief with prior loperamide use.”
Disclosure: This clinical trial was supported by Allergan plc, Dublin, Ireland. Several study authors declared affiliations with the pharmaceutical industry.
Brenner DM, Sayuk GS, Gutman CR, et al. Efficacy and safety of eluxadoline in patients with irritable bowel syndrome with diarrhea who report inadequate symptom control with loperamide: RELIEF phase 4 study [published online July 26, 2019]. Am J Gastroenterol. doi: 10.14309/ajg.0000000000000327