Eluxadoline Efficacy in IBS-D Patients Who Report Prior Loperamide Use

Abstract

Objectives: Irritable bowel syndrome with diarrhea (IBS-D) is often managed with over-the-counter therapies such as loperamide, though with limited success. This analysis evaluated the efficacy of eluxadoline in patients previously treated with loperamide in two phase 3 studies.

Methods: Adults with IBS-D (Rome III criteria) were enrolled and randomized to placebo or eluxadoline (75 or 100 mg) twice daily for 26 (IBS-3002) or 52 (IBS-3001) weeks. Patients reported loperamide use over the previous year and recorded their rescue loperamide use during the studies. The primary efficacy end point was the proportion of patients with a composite response of simultaneous improvement in abdominal pain and reduction in diarrhea.

Results: A total of 2,428 patients were enrolled; 36.0% reported prior loperamide use, of whom 61.8% reported prior inadequate IBS-D symptom control with loperamide. Among patients with prior loperamide use, a greater proportion treated with eluxadoline (75 and 100 mg) were composite responders vs. those treated with placebo with inadequate prior symptom control, over weeks 1-12 (26.3% (P=0.001) and 27.0% (P<0.001) vs. 12.7%, respectively); similar results were observed over weeks 1-26. When daily rescue loperamide use was imputed as a nonresponse day, the composite responder rate was still higher in patients receiving eluxadoline (75 and 100 mg) vs. placebo over weeks 1-12 (P<0.001) and weeks 1-26 (P<0.001). Adverse events included nausea and abdominal pain.

Conclusions: Eluxadoline effectively and safely treats IBS-D symptoms of abdominal pain and diarrhea in patients who self-report either adequate or inadequate control of their symptoms with prior loperamide treatment, with comparable efficacy and safety irrespective of the use of loperamide as a rescue medication during eluxadoline treatment.

Figure 1

Composite response rates by prior symptom control with loperamide during (a) weeks 1–12 and (b) weeks 1–26: pooled analysis for eluxadoline phase 3 studies. BID, twice daily. *P≤0.001 vs. placebo; ^†P<0.01 vs. placebo; ^‡P<0.05 vs. placebo.

Figure 2

Response rates for improvement in stool consistency by prior symptom control with loperamide during (a) weeks 1–12 and (b) weeks 1–26: pooled analysis for eluxadoline phase 3 studies. BID, twice daily. *P≤0.001 vs. placebo; ^†P<0.01 vs. placebo; ^‡P<0.05 vs. placebo.

Figure 3

Response rates for improvement in abdominal pain by prior symptom control with loperamide (a) during weeks 1–12 and (b) weeks 1–26: pooled analysis for eluxadoline phase 3 studies. BID, twice daily. *P≤0.001 vs. placebo; ^†P<0.01 vs. placebo; ^‡P<0.05 vs. placebo.

Figure 4

Composite response rates in patients not using any rescue loperamide during (a) weeks 1–12 and (b) weeks 1–26: pooled analysis for eluxadoline phase 3 studies. BID, twice daily. *P<0.001 vs. placebo; ^†P<0.01 vs. placebo; P values calculated using χ² test statistic.

Figure 5

Composite response rates with imputed nonresponse when rescue loperamide was used during (a) weeks 1–12 and (b) weeks 1–26: pooled analysis for eluxadoline phase 3 studies. BID, twice daily. *P<0.001 vs. placebo; P values calculated using χ² test statistic. Patients were assumed to be nonresponders for the daily response on any day during weeks 1–12 and weeks 1–26 where rescue loperamide was used. Percentages calculated from total number of patients receiving placebo or eluxadoline 75 or 100 mg.