Abstract
Background
Irritable bowel syndrome with diarrhea (IBS-D) is characterized by recurrent abdominal pain and diarrhea. Eluxadoline (ELX) is a mixed µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist approved for the treatment of IBS-D in adults.
Aims
To examine the efficacy of ELX for treating abdominal pain in adults with IBS-D reporting inadequate response to loperamide.
Methods
In a Phase 4 clinical trial (RELIEF) conducted in Canada and the US, adults with IBS-D who reported inadequate symptom control with loperamide in the previous 12 months were randomized to oral ELX (100 mg twice daily) or placebo (PBO) for 12 weeks. Patients recorded their daily IBS-D symptoms including worst abdominal pain (WAP) [reported on a scale of 0–10, where 0 is equal to no pain and 10 is equal to the worst imaginable pain]. Baseline WAP score was calculated as an average score in the week before randomization. Proportions of patients achieving ≥30%, ≥40%, and ≥50% improvements in WAP scores from baseline for ≥50% of treatment days were calculated weekly, for the 12-week treatment period and for each 4-week interval (Weeks 1–4, Weeks 5–8, and Weeks 9–12).
Results
Overall, 346 patients were randomized, 174 to PBO and 172 to ELX. Patients’ WAP scores decreased over time, with a notably lower WAP score in the ELX group after approximately 3 weeks and maintained over 12 weeks of treatment (Figure). Patients in the ELX group reported higher mean weekly WAP scores compared to placebo from baseline to Week 2, and lower scores from Weeks 3 to 12. The proportion of WAP responders at Weeks 1–12 and Weeks 5–8 were significantly higher with ELX than with PBO at all three pain improvement thresholds, while at Weeks 9–12, the proportion of WAP responders was only significantly greater in the ELX group compared to the PBO group at the ≥50% improvement threshold (Table).
Conclusions
A significantly greater percentage of patients treated with ELX experienced improvements in the abdominal pain component of their IBS-D over a 12-week treatment period, suggesting that ELX is effective for treating abdominal pain in patients with IBS-D who have reported inadequate response to loperamide.
This study was supported by Allergan plc. Writing assistance by Complete HealthVizion based on detailed feedback from all authors, funded by Allergan plc.
Proportion of WAP responders at ≥30%, ≥40%, and ≥50% improvement from baseline thresholds
| (%) | ≥30% WAP improvement responders a | ≥40% WAP improvement responders a | ≥50% WAP improvement responders a | |||
|---|---|---|---|---|---|---|
| Placebo | Eluxadoline | Placebo | Eluxadoline | Placebo | Eluxadoline | |
| Weeks 1–12 | 37.4 | 50.6* | 31.0 | 43.6* | 23.6 | 35.5* |
| Weeks 1–4 | 33.9 | 39.0 | 25.9 | 30.2 | 18.4 | 22.7 |
| Weeks 5–8 | 37.9 | 54.7** | 31.6 | 45.9** | 25.9 | 37.8* |
| Weeks 9–12 | 42.0 | 47.1 | 35.1 | 44.8 | 28.7 | 43.0** |
aDefined as patients achieving the defined percent improvement from baseline in WAP for ≥50% of treatment days; *p<0.05 vs. placebo; **p≤0.01 vs. placebo; WAP, worst abdominal pain
Funding Agencies
Allergan plc