Eluxadoline has a dual mechanism of action in the gut, acting as both a mu and kappa opioid receptor agonist and a delta opioid antagonist, slowing down GI transit and thus increasing absorption and reducing defaecation.
Further informationView eluxadoline drug record
"IBS-D can have a significant and profound impact on patient quality of life, often manifested through dietary restrictions, emotional distress and activity limitations," said Professor Jan Tack, Professor of Internal Medicine at the University of Leuven. "Truberzi, as the only licensed treatment for IBS-D, is a welcome new treatment option for patients in Europe."
Reduced abdominal pain and diarrhoea
Researchers evaluated the efficacy and safety of eluxadoline in two double-blind, placebo-controlled phase III trials, IBS-3001 and IBS-3002, in adults with IBS-D (n=2427).
Patients met Rome III criteria for IBS and were required to report an average worst abdominal pain score of >3 on a scale of 0 to 10 (0 indicating no pain and 10 the worst imaginable pain), an average score for stool consistency of ≥5.5 on the Bristol Stool Form Scale (BSFS) which ranges from 1 to 7 (1 indicating hard stools and 7 watery diarrhoea), a score of ≥5 on the BSFS for at least 5 days and an average IBS-D global symptom score of ≥2 (0 indicating no symptoms of IBS-D and 4 very severe symptoms).
For the collection of efficacy data, patients were randomised to receive eluxadoline 75mg or 100mg or placebo, twice daily for 26 weeks. The primary efficacy endpoint was the proportion of patients who recorded a reduction of ≥30% from their average baseline score for their worst abdominal pain for at least 50% of the treatment days and, on the same days, a daily stool-consistency score of <5.
Both doses of eluxadoline were shown to be significantly superior to placebo. At week 26, the proportion of patients who experienced an endpoint response in IBS-3001 was 23.4% with the 75mg dose and 29.3% with the 100mg dose compared to 19.0% with placebo (p=0.11 and p<0.001, respectively). The corresponding rates in IBS-3002 were 30.4% and 32.7% versus 20.2% (p=0.001 and p<0.001, respectively).
Risk of pancreatitis
The most common adverse effects seen in the two trials were nausea, constipation and abdominal pain. Owing to its limited bioavailability, the pharmacodynamic activity of eluxadoline is based predominantly on local action within the GI tract, reducing the risk of CNS-mediated adverse effects.
Five cases of pancreatitis (0.3%) and 8 cases of abdominal pain with elevated levels of hepatic enzymes (0.5%) occurred in the studies. Nine of these 13 cases were judged to be associated with spasm of the sphincter of Oddi.
Eluxadoline is contraindicated in patients with known or suspected sphincter of Oddi dysfunction, those with biliary tract or pancreatic disease, and those who are missing a gallbladder.
Patients receiving the drug should be instructed to stop treatment and seek medical attention if they experience symptoms suggestive of sphincter of Oddi spasm or pancreatitis, such as acute worsening abdominal pain. Prescribers should advise all patients taking eluxadoline to avoid excessive alcohol use during treatment.