SOURCE: Lembo AJ, et al. Eluxadoline for irritable bowel syndrome with diarrhea. N Engl J Med 2016;374:242-253.
The burden of suffering sustained by persons with diarrhea-predominant irritable bowel syndrome (IBS-D) is substantial, and clinicians often underestimate the condition. While OTC remedies (e.g., loperamide, fiber) may provide some relief for IBS-D, residual symptoms continue to plague most patients.
Eluxadoline is a recently FDA-approved pharmacologic treatment for IBS-D. Mu-receptors are prominently active in the GI system, as evidenced by the commonplace development and persistence of constipation in patients using opioid analgesics. The primary mechanism of eluxadoline is peripheral (i.e., not in the CNS) mu-receptor mediated reduction in colonic visceral hypersensitivity. At the same time, an additional mechanism of eluxadoline — delta-receptor antagonism — appears to reduce the degree of constipation typically induced by pure mu-receptor agonists.
Lembo et al reported results from placebo-controlled trials of eluxadoline in IBS-D (n = 2427). The primary outcome was the number of patients who experienced decreased abdominal pain as well as improved stool consistency for at least half the days throughout the studies (one study lasted 12 weeks, the other lasted 26 weeks).
Eluxadoline demonstrated a modest but statistically significant greater ability to reach the primary endpoint and was generally well tolerated. Cases of pancreatitis occurred during eluxadoline treatment, but not during placebo treatment. Because these cases occurred in post-cholecystectomy patients or in persons who used excessive alcohol, until more information is available, clinicians would be wise to avoid eluxadoline in these populations.
Eluxadoline demonstrated a modest but statistically significant greater ability to reach the primary endpoint and was generally well tolerated.
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