In patients with irritable bowel syndrome with diarrhea (IBS-D), eluxadoline is a safe, effective, and tolerable alternative treatment for those who report inadequate symptom relief with loperamide, according to study results published in the American Journal of Gastroenterology.
Researchers used data from the phase 4 RELIEF trial (NCT02959983) to assess the safety, efficacy, and tolerability of twice-daily 100 mg eluxadoline in patients with IBS-D who reported inadequate symptom control with loperamide. Loperamide, is one of the most commonly used agents for the management of IBS-D despite the recent American College of Gastroenterology IBS Monograph strongly recommending against it as an IBS therapy.
For this double-blinded, randomized, placebo-controlled, prospective, multicenter, multinational study, researchers randomly assigned 346 patients to receive either a placebo or eluxadoline for 12 weeks; 85.3% of these participants completed the trial. Data were collected from 82 study sites between November 2016 to January 2018 across the United States and Canada.
At baseline, patients in both groups were similar; the mean age was 44 years, the group was 70% women, and the median time since IBS-D diagnosis was 6 years. Prior to randomization, both groups reported similar use of loperamide (15.5% vs 13.4% in the placebo and treatment groups). In approximately 85% of participants, loperamide was taken on an as-needed basis, whereas 11% used loperamide daily. In the placebo and treatment groups, 46.5% and 39.4% of patients used loperamide for longer than 1 year.
Investigators found that a “statistically significant greater proportion” of patients in the eluxadoline group achieved the primary composite responder end point of ≥40% worst abdominal pain score improvement and daily stool consistency response (22.7% vs 10.3% in the treatment vs placebo groups; P =0.002). During each 4-week analysis interval, more patients in the treatment group met the primary end point as well (weeks 1-4: 14% vs 6.9%, P =0.03; weeks 5-8: 26.7% vs 14.9%, P =0.006; weeks 9-12: 30.8% vs 16.7%, P =0.002).
In terms of secondary efficacy outcomes, more patients in the treatment group met the criteria for weekly composite responders at weeks 4 through 7, 9, 11, and 12, compared with the placebo group. Eluxadoline therapy also led to a “significantly higher proportion” of ≥6-week composite responders.
Additionally, a significantly greater proportion of patients in the treatment group met the abdominal pain response end point during the 12-week analysis period compared with the placebo group (43.6% vs 31%, P =0.02), and improvements in worst abdominal pain response scores were also noted during each 4-week interval in the treatment group.
Treatment-emergent adverse events were reported in both groups: 112 and 124 in the placebo and treatment groups, respectively. The proportion of treatment-emergent adverse event reporting was comparable between the 2 groups, although patients in the eluxadoline group experienced more events leading to premature treatment discontinuation than the placebo group. Gastrointestinal adverse events were the most common treatment-emergent adverse events, with 17% reported in the treatment group vs 6.4% in the placebo group.
“Results of the current study demonstrate positive treatment benefits for eluxadoline over placebo in patients with IBS-D,” the researchers concluded. “This study prospective validates previous findings revealing eluxadoline to be a safe, effective IBS-D treatment in patients reporting inadequate symptom relief with prior loperamide use.”
This clinical trial was supported by Allergan plc. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
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. Am J Gastroenterol. 2019;114(9):1502-1511.