Chisom Anosike, LECOM School of Pharmacy
Gastrointestinal diseases affect more than 60 to 70 million Americans annually. The United State spends approximately $142 billion per year in direct and indirect costs due to gastrointestinal diseases.  Symptoms of irritable bowel syndrome (IBS) are stated to include recurring abdominal pain, bloating, and loose, frequent stools in the absence of structural, inflammatory, or biochemical abnormalities. Diarrhea with IBS has been considered to be correlated with impairment in quality of life and a substantial financial burden on society because of reduced work productivity. 
|Title: Eluxadoline for Irritable Bowel Syndrome with Diarrhea|
|Design||Two randomized, double-blind, placebo-controlled, parallel-group, multicenter trials; N = 2,428|
|Objective||To evaluate the clinical response of patients with IBS with diarrhea to eluxadoline, as compared with placebo, through 26 weeks and to evaluate the safety of eluxadoline up to 52 weeks|
|Study Groups||Eluxadoline 75 mg (n = 810)
Eluxadoline 100 mg (n = 808)
Placebo (n = 809)
|Methods||Patients who were 18 to 80 years of age, who had IBS with diarrhea were enrolled in this trial. During the first 26 weeks of the IBS-3001 trial and first 30 weeks of the IBS-3002 trial, assessments by patients were recorded daily that included the score for the worst abdominal pain, the extent of discomfort and bloating, a stool consistency score, the number of bowel movements and whether they were associated with urgency or fecal incontinence, and the IBS-D (irritable bowel syndrome with diarrhea) global symptom score. Additionally, adequate relief of IBS symptoms was assessed weekly. Patient visits occurred at weeks 2, 4, 8, 12, 18, 26, 36, 44, and 52.|
|Duration||May 29, 2012 through July 29, 2014|
|Primary Outcome Measure||Proportion of patients who had a composite response, that is, patients who recorded a reduction of abdominal pain ≥ 30% on ≥ 50% of the days from their average baseline score for worst abdominal pain, and a stool-consistency score of < 5|
|IBS-3001 trial (n = 1,282)||IBS- 3002 trial (n = 1,146)|
|Placebo (n= 427)||Eluxadoline 75mg (n= 429)||Eluxadoline 100mg (n= 426)||Placebo (n= 382)||Eluxadoline 75mg (n= 381)||Eluxadoline 100mg (n= 382)|
|Sex- no. of patients %:|
|History of cholecystectomy- no. of patients %||89 (20.8)||85 (19.8)||98 (23.0)||69 (18.1)||81 (21.3)||74 (19.3)|
|Mean daily scores:|
|Abdominal bloating score||6.1||5.9||5.8||5.7||5.7||5.6|
|IBS-diarrhea global symptom score||2.9||2.8||2.9||2.8||2.8||2.8|
|IBS-quality of life (QOL) questionnaire score||44.1||46.2||45.9||46.7||50.6||48.7|
|Results||For weeks one through twelve, patients in the eluxadoline groups (75 mg and 100 mg) and in the placebo group reached the primary end point were:
IBS-3001 trial: 23.9% with the 75-mg dose and 25.1% with the 100-mg dose versus 17.1% with placebo; p= 0.01 and p= 0.004, respectively
IBS-3002 trial: 28.9% with the 75-mg dose and 29.6% with the 100-mg dose versus 16.2% with placebo; p< 0.001 for both comparisons
For weeks one through 26, the corresponding rates in IBS-3001 were 23.4% and 29.3% versus 19.0% (p= 0.11 and p< 0.001, respectively), and the corresponding rates in IBS-3002 were 30.4% and 32.7% versus 20.2% (p= 0.001 and p< 0.001, respectively).
|Adverse Events||Common Adverse Events: nausea (8.1% in 75 mg group, 7.5% in 100 mg group), constipation (7.4% in 75 mg group, 8.6% in 100 mg group), and abdominal pain (5.8% in 75 mg group, 7.2% in 100 mg group)|
|Serious Adverse Events: abdominal pain with elevated levels of hepatic enzymes (0.1% in 75 mg group, 0.8% in 100 mg group) and pancreatitis (0.2% in 75 mg group, 0.3% in 100 mg group)|
|Percentage that Discontinued due to Adverse Events: due to constipation (1.1% in 75 mg group, 1.7% in 100 mg group), nausea (0.6% in 75 mg group, 0% in 100 mg group)|
|Study Author Conclusions||Eluxadoline is a new therapeutic agent that reduced symptoms of IBS with diarrhea in men and women, with sustained efficacy over six months in patients who received the 100-mg dose twice daily.|
In these studies, eluxadoline was effective in relieving abdominal pain and diarrhea. The primary outcome measure required simultaneous improvement in the daily scores for the worst abdominal pain and stool consistency on the same day for at least 50% of the days assessed; this end point is presently one of those recommended by the regulatory agencies in the United States and Europe to show treatment effect in trials involving patients with IBS and diarrhea.
- Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology. 2012;143(5):1179-87.e1-3.
- Lembo AJ, Lacy BE, Zuckerman MJ, et al. Eluxadoline for Irritable Bowel Syndrome with Diarrhea. N Engl J Med. 2016;374(3):242-53.