Eluxadoline offers symptom relief from IBS with diarrhoea
Treatment with eluxadoline, a new oral medication, relieved two major symptoms of irritable bowel syndrome with diarrhoea (IBS-D) — abdominal pain and diarrhoea, according to a study based on two phase III randomized controlled trials. [N Engl J Med 2016;374:242-253]
Currently available treatment options for IBS-D are limited, particularly options that relieve both abdominal pain and diarrhoea. Study co-author Professor Marc Zuckerman, chief of the Division of Gastroenterology at Texas Tech University Health Sciences Center in El Paso, Texas, US, said eluxadoline provides a new option for treating IBS-D patients that do not respond to standard management with lifestyle changes and over-the-counter medication.
“This is a new first-in-class drug, with a unique mechanism of action in that it is a mu opioid receptor (OR) agonist, a kappa OR agonist, and a delta OR antagonist, targeting receptors in the gastrointestinal (GI) tract,” said Zuckerman.
Co-author Dr. Brian Lacy, professor of medicine and chief of the Section of Gastroenterology and Hepatology at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, US, said due to eluxadoline’s mixed action on different subtypes of OR and its very limited absorption from the GI tract, it should not cause any problems typical of opioids, such as somnolence or addiction.
The researchers found that by week 12, abdominal pain and diarrhoea improved in 24 (study 1, p=0.01) and 29 (study 2, p<0.001) percent of patients given the 75 mg dose of eluxadoline, and 25 (study 1, p=0.004) and 30 (study 2, p<0.001) percent of patients taking 100 mg dose; compared with the placebo group which saw an improvement in 17 (study 1) and 16 (study 2) percent of the patients. Similar efficacy results were sustained over the 6 month treatment period of the studies (study 1: p=0.11 for 75 mg, p<0.001 for 100 mg; study 2: p=0.001 for 75 mg, p<0.001 for 100 mg). The study is sponsored by Furiex Pharmaceuticals, an affiliate of Allergan.
Common adverse events associated with eluxadoline treatment were constipation, nausea, and abdominal pain; while the most serious adverse event documented was pancreatitis, affecting 0.3 percent of the 1,666 patients enrolled in the safety population. However, the authors noted that the discontinuation rate due to adverse reactions was low.
Nonetheless, erring on the side of caution, Zuckerman advised clinicians to keep in mind three conditions before prescribing eluxadoline: sphincter of Oddi dysfunction, pancreatitis, and alcohol abuse. Additionally, he said eluxadoline should be avoided in patients with chronic constipation.
“If [the patients] have a history of gallbladder problems (known stones or sludge) or biliary colic, I also caution them that they may be at increased risk,” Lacy agreed.
Lacy said that while no medication has been shown to improve IBS-D symptoms in all groups of patients, eluxadoline was effective for both men and women as well as young and old patients, in relieving abdominal pain and diarrhoea. He said the drug also worked well for IBS-D patients who have previously received but failed the diarrhoea medication loperamide.
Thus far, there are no direct comparisons with similar prescription drugs for this condition, such as rifaximin or alosetron. Lacy said it would be interesting to do a direct comparison study of eluxadoline and alosetron and/or even rifaximin in the future.