1. Eluxadoline appeared to be effective in relieving symptoms of patients with irritable bowel syndrome (IBS) with diarrhea.
2. In these randomized controlled studies, among patients treated with IBS with diarrhea treated with eluxadoline, there were significant improvements in abdominal pain and stool consistency.
Evidence Rating Level: 1 (Excellent)
Study Rundown: IBS, the most common diagnosis in gastroenterology practices, is a poorly understood condition with important public health impacts. Eluxadoline is a peripherally acting mixed m- and k-opioid receptor agonist and d-opioid receptor antagonist. A prior phase 2 study showed that a significantly greater proportion of patients treated with eluxadoline experienced reduction in symptoms of IBS with diarrhea compared to placebo.
In this set of two randomized controlled studies, the authors evaluated the clinical response over 26 weeks of patients with IBS with diarrhea who received either eluxadoline or placebo, with safety monitoring occurring through 52 weeks. Over 26 weeks, among those treated with 100mg twice daily of the study drug, there were statistically significant decreases in the proportion of patients who had a composite response of decrease in abdominal pain and improvement in stool consistency.
These results are effected by the large sample sizes and the randomized, controlled design, that provided support for an emerging therapy for a poorly understood medical condition. However, it is worth noting the substantial improvement of symptoms of patients in the placebo arms. Future studies will help determine the risk/benefit profile of starting these medications and help define subpopulations with highest likelihood of benefit.
In-Depth [randomized controlled trial]: This study involved two randomized controlled studies with 2427 adults who had IBS with diarrhea who were assigned to receive eluxadoline at a dose of 75mg or 100mg or placebo twice daily for 26 weeks (trial #1) or 52 weeks (trial #2, for adverse event monitoring). The primary end point was the proportion of patients achieving a composite response of decrease in abdominal pain (³30% reduction in abdominal pain score from baseline) and improvement in stool consistency for at least 50% of the days from weeks 1 through 12 or weeks 1 through 26. Patients with a history of IBD or celiac disease, thyroid abnormalities, alcohol abuse or binge drinking, pancreatitis, sphincter of Oddi dysfunction, or allergies to opioids were excluded from the study. In the intention-to-treat analysis, from weeks 1 through 12, patients receiving eluxadoline at a dose of 75mg or 100mg twice daily had a significantly improved primary end point (in trial #1, 23.9% with 75-mg dose; 25.1% with 100-mg dose vs. 17.1% with placebo, p=0.01 and p=0.004 respectively; in trial #2, 28.9% and 29.6% respectively, compared to placebo of 16.2%, p<0.001 for both comparisons).
In one of the studies, comparisons for weeks 1 through 26 were not significantly different for the 75mg eluxadoline group versus placebo (p=0.11); however, there was a statistically significant benefit of eluxadoline at the higher dose of 100mg twice daily (p<0.001 for both comparisons) across 26 weeks of follow-up. The most common adverse events affecting patients treated with eluxadoline were nausea (7.7%), constipation (8.0%), and abdominal pain (6.5%); five patients in the treatment groups developed pancreatitis, while none in the placebo group were affected.
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