IBS-D drug worked better than placebo in patients already using loperamide

The industry-funded analysis looked at two phase 3 randomized, controlled trials of patients who were randomized to placebo or eluxadoline (75 or 100 mg) twice daily for 26 or 52 weeks.


Eluxadoline, which was approved by the FDA in 2015, may effectively and safely treat symptoms of irritable bowel syndrome with diarrhea (IBS-D) in patients who self-report either adequate or inadequate control of their symptoms with loperamide, according to an industry-funded analysis of two phase 3 randomized, controlled trials.

Researchers enrolled 2,428 patients with IBS-D (Rome III criteria), of whom 36.0% reported using loperamide. Of that group, 61.8% reported prior inadequate IBS-D symptom control. Patients were randomized to placebo or eluxadoline (75 or 100 mg) twice daily for 26 or 52 weeks. They reported loperamide use over the previous year and recorded using rescue loperamide. Furiex Pharmaceuticals, which manufactures eluxadoline, funded the research and was responsible for design and data analysis, in collaboration with the authors.

The mean daily worst abdominal pain score was >6 across all treatment groups. The average number of daily bowel movements ranged from 4.7±2.2 to 5.0±3.0. Patients were defined as responders if they achieved ≥30% improvement in abdominal pain, with a simultaneous improvement in symptoms of diarrhea (assessed using the Bristol Stool Scale) on ≥50% of days during the 12- or 26-week study period.

Results were published online by the American Journal of Gastroenterology on April 18.

Among patients with prior loperamide use and inadequate symptom control, a significantly greater proportion treated with eluxadoline (75 and 100 mg) responded compared to patients treated with placebo over weeks 1 to 12 (26.3%, 27.0%, and 12.7%; P=0.001 and P<0.001 compared to placebo, respectively). Similar results were seen over weeks 1 to 26. Also, among patients reporting prior loperamide use and adequate symptom control, a significantly greater proportion of patients treated with eluxadoline, 100 mg, responded compared with those treated with placebo (41.8% vs. 25.0%; P=0.006).

A significantly greater proportion of patients treated with eluxadoline were responders based on stool consistency over weeks 1 to 12 compared with those treated with placebo (eluxadoline, 100 mg: 35.6%; eluxadoline, 75 mg: 33.3%; placebo: 19.3%; P<0.001 and P=0.002 compared to placebo, respectively). Response rates were similar among patients with adequate symptom control at baseline (eluxadoline, 100 mg: 49.2% responded; eluxadoline, 75 mg: 47.9%; placebo: 33.6%; P=0.012 and P=0.037 compared to placebo, respectively). Similar findings were also observed for weeks 1 to 26.

Approximately one-quarter of patients reported use of rescue loperamide through weeks 1 to 12, with a slightly greater percentage of patients in the placebo group using it compared with patients treated with either dose of eluxadoline, 75 or 100 mg (31.3%, 26.7%, and 25.6%, respectively). Through weeks 1 to 26, more rescue use was reported in the placebo group than in either of the eluxadoline groups, 75 or 100 mg (36.0%, 32.8%, and 31.3%, respectively).

The authors noted that their sample size was large, that the analyses were prospective, and that previous loperamide use was based on self-report. However, they concluded, “These findings are clinically relevant as they demonstrate to health-care providers that eluxadoline is an efficacious and safe treatment option for the majority of patients diagnosed with IBS-D, irrespective of prior treatment experience with loperamide.”