Potential Alternative for IBS-D Patients Whose Current Treatment Offers Poor Symptom Relief

As HCPLive reported earlier this year, data from a pair of phase 3 clinical trials showed that treatment with eluxadoline, a locally active, mixed mu-opioid receptor (µOR) agonist and delta-opioid receptor (δOR) antagonist, improved symptoms in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). In the studies, Eluxadoline met the primary objective of a pre-defined composite endpoint (CEP) of simultaneous improvements in stool consistency and abdominal pain, as well as improvements in urgency, frequency, and adequate relief.

In study results presented at the American College of Gastroenterology 2014 Annual Scientific Meeting and Postgraduate Course, researchers looked at a subset of participants in the phase 3 trials who had reported using the antidiarrhea medication loperamide during the year prior to enrolling in the trials. They looked at how often patients reported using loperamide (ie as an acute “rescue” medication or as a chronic “controller” medication) and compared the CEP response rates between patients who had previously experienced adequate control of IBS-D symptoms with loperamide and those who did not.

Prior to enrollment in the phase 3 trials, participants were asked whether they used loperamide acutely or chronically in the previous year, and whether it had provided adequate control of IBS-D symptoms. Once patients were enrolled and randomized into the trials, they were permitted to use loperamide as rescue therapy.

A total of 2,423 patients were enrolled in the phase 3 trials. Of these, 873 used loperamide in the year prior to enrollment, with 751 (86%) using it acutely and 122 (14%) using it chronically. More than one-third (38%) of users reported adequate IBS-D symptom control with loperamide; 61% reported inadequate symptom control.

The researchers divided the participants who used loperamide into 2 cohorts (those who achieved symptom control and those who did not) and looked at differences in CEP response rates between patients in the trials who received placebo and those who received eluxadoline. Patients who did not experience symptom control with loperamide had a lower placebo response rate compared with patients who had achieved symptom control with loperamide. Response rates in eluxadoline-treated patients who had achieved symptom control were 37% (eluxadoline 75 mg) and 42% (eluxadoline 100 mg). In eluxadoline-treated patients who had not achieved prior symptom control, response rates were 26% (eluxadoline 75 mg) and 27% (eluxadoline 100 mg).

Use of loperamide as rescue medication during the trials was “infrequent and occurred at comparable rates in both eluxadoline and placebo groups,” the authors wrote.

In their summary of these results, the authors noted that both patient subsets (those who had achieved prior symptom control with loperamide and those who had not) “demonstrated significant efficacy with eluxadoline,” suggesting that there is “differentiation between eluxadoline and loperamide, and that eluxadoline may be useful in patients whose symptoms are not adequately managed with loperamide.”