Using Radar Plots to Display Disparate Global Effects of Eluxadoline in Patients With Irritable Bowel Syndrome With Diarrhea

Abstract

Introduction: Eluxadoline (ELX), a locally active mixed μ-opioid receptor (OR) and κ-OR agonist and δ-OR antagonist, is approved for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults based on results of two Phase 3 studies.1 IBS-D patients (pts) experience a range of symptoms, and presentation of data in radar plots can facilitate understanding of improvements seen with ELX across a disparate range of efficacy measures. Methods: Two double-blind, placebo (PBO)-controlled, Phase 3 clinical trials (IBS-3001 and IBS-3002) randomized pts meeting Rome III criteria for IBS-D to twice-daily treatment with ELX 75 or 100 mg or PBO. Pts rated IBS symptoms daily: abdominal pain, abdominal bloating, and abdominal discomfort (0-10 scales), stool consistency (Bristol Stool Scale [BSS]; 1-7 scale), and IBS-D Global Symptom Score (GSS; 0-5 scale). Pts reported number of bowel movements (BMs) and urgency episodes daily. Adequate relief (AR) of IBS symptoms was assessed weekly. Response rates over Weeks 1-26 and change from baseline to Week 26 are displayed in radar plot format for these endpoints: primary efficacy composite response, based on simultaneous daily improvement of ≥30% in abdominal pain score vs. baseline and BSS score < 5 with ≥50% of days demonstrating a response; stool consistency response as per the primary endpoint; abdominal pain response calculated using criteria of ≥30%, ≥40%, or ≥50% improvement vs. baseline; urgency-free response calculated using criteria of ≥50% or ≥75% of days with no urgency episode; AR response defined as a weekly “yes” response for ≥50% of treatment weeks. Results: The pooled intent-to-treat analysis set included 2423 pts. Baseline characteristics were similar across treatment groups (Table). Treatment with ELX improved responder proportions vs. PBO over Weeks 1-26 for the composite endpoint,1 stool consistency, urgency-free days (≥50% and ≥75% of days), AR, and abdominal pain (≥30%, ≥40%, and ≥50% improvement vs. baseline) [Figure 1]. Changes from baseline to Week 26 in GSS, abdominal discomfort, abdominal pain, abdominal bloating, and number of BMs were greater with ELX vs. PBO (Figure 2).FigureFigureTable: No Caption availableConclusion: Presentation in radar plots facilitates interpretation of efficacy data across multiple domains, demonstrating that ELX treatment led to improvements vs. PBO across 13 endpoints representing the range of symptoms experienced by IBS-D pts. 1. Lembo AJ et al. N Engl J Med 2016;374:242-253.