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Eluxadoline: A Review in Diarrhoea-Predominant Irritable Bowel Syndrome

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Abstract

Eluxadoline (Truberzi®) is an orally administered, minimally absorbed agent that acts locally in the gastrointestinal tract as a mixed µ-opioid receptor agonist and δ-opioid receptor antagonist. The randomized, double-blind, placebo-controlled, multinational, phase 3 IBS-3001 and IBS-3002 trials examined the efficacy of eluxadoline in patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). The composite response rate (i.e. the proportion of patients with improvement in both worst abdominal pain and stool consistency on ≥50% of days; primary endpoint), was significantly higher in patients receiving eluxadoline 100 mg twice daily than in those receiving placebo after 12 and 26 weeks’ therapy. Other abdominal and bowel symptoms (e.g. bloating, urgency, frequency of bowel movement) and health-related quality of life scores were also improved with eluxadoline. Eluxadoline was generally well tolerated in patients with IBS-D. Constipation was the most commonly occurring adverse event, although no serious constipation events were reported. Pancreatitis and adverse events consistent with sphincter of Oddi spasm were uncommon. In conclusion, eluxadoline is a new option to consider in the treatment of adult patients with IBS-D.

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References

  1. Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150:1393–407.

    Article  Google Scholar 

  2. Lacy BE. Emerging treatments in neurogastroenterology: eluxadoline—a new therapeutic option for diarrhea-predominant IBS. Neurogastroenterol Motil. 2016;28(1):26–35.

    Article  CAS  PubMed  Google Scholar 

  3. Breslin HJ, Diamond CJ, Kavash RW, et al. Identification of a dual δ OR antagonist/µ OR agonist as a potential therapeutic for diarrhea-predominant irritable bowel syndrome (IBS-d). Bioorg Med Chem Lett. 2012;22(14):4869–72.

    Article  CAS  PubMed  Google Scholar 

  4. European Medicines Agency. Truberzi (eluxadoline): EU summary of product characteristics. 2016. http://www.ema.europa.eu/. Accessed 1 Feb 2017.

  5. Wade PR, Palmer JM, McKenney S, et al. Modulation of gastrointestinal function by MuDelta, a mixed µ opioid receptor agonist/µ opioid receptor antagonist. Br J Pharmacol. 2012;167(5):1111–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sobolewska-Włodarczyk A, Włodarczyk M, Storr M, et al. Clinical potential of eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome. Ther Clin Risk Manag. 2016;12:771–5.

    PubMed  PubMed Central  Google Scholar 

  7. Fujita W, Gomes I, Dove LS, et al. Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers. Biochem Pharmacol. 2014;92(3):448–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Levy-Cooperman N, McIntyre G, Bonifacio L, et al. Abuse potential and pharmacodynamic characteristics of oral and intranasal eluxadoline, a mixed µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist. J Pharmacol Exp Ther. 2016;359(3):471–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Davenport JM, Hunt T, Dove LS. Eluxadoline has no effect on cardiac repolarization [abstract no. PII-017]. Clin Pharmacol Ther. 2016;99(Suppl 1):S79.

    Google Scholar 

  10. Davenport JM, Marbury T, Berg J, et al. Effect of hepatic impairment on eluxadoline pharmacokinetics [abstract no. PI-023]. Clin Pharmacol Ther. 2016;99(Suppl 1):S37.

    Google Scholar 

  11. Davenport JM, Covington P, Bonifacio L, et al. Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015;55(5):534–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dove LS, Lembo A, Randall CW, et al. Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013;145(2):329–38.

  13. Lembo AJ, Lacy BE, Zuckerman MJ, et al. Eluxadoline for irritable bowel syndrome with diarrhea. N Engl J Med. 2016;374(3):242–53.

    Article  CAS  PubMed  Google Scholar 

  14. Lacy B, Chey W, Lembo A, et al. Eluxadoline demonstrates efficacy for the treatment of irritable bowel syndrome (IBS) with diarrhoea (IBS-D) among multiple clinically relevant patient subgroups [abstract no. OC-070]. Gut. 2016;65(Suppl 1):A42–3.

  15. Lacy BE, Chey WD, Cash BD, et al. Eluxadoline efficacy in IBS-D patients who report prior loperamide use. Am J Gastroenterol. 2017. doi:10.1038/ajg.2017.72.

    Google Scholar 

  16. Chey WD, Dove LS, Andrae DA, et al. Early response predicts a sustained response to eluxadoline in patients with irritable bowel syndrome with diarrhoea in two phase 3 studies. Aliment Pharmacol Ther. 2017;45(10):1319–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cash BD, Lacy BE, Schoenfeld PS, et al. Safety of eluxadoline in patients with irritable bowel syndrome with diarrhea. Am J Gastroenterol. 2017;112(2):365–74.

    Article  CAS  PubMed  Google Scholar 

  18. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102–11.

    Article  PubMed  Google Scholar 

  19. Fant RV, Henningfield JE, Cash BD, et al. Eluxadoline demonstrates a lack of abuse potential in phase 2 and 3 studies of patients with irritable bowel syndrome with diarrhea. Clin Gastroenterol Hepatol. 2017. doi:10.1016/j.cgh.2017.01.026.

    PubMed  Google Scholar 

  20. Ford AC, Moayyedi P, Lacy BE, et al. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(Suppl 1):S2–26.

    Article  PubMed  Google Scholar 

  21. Lacy BE, Moreau JC. Diarrhea-predominant irritable bowel syndrome: diagnosis, etiology, and new treatment considerations. J Am Acad Nurse Pract. 2016;28(7):393–404.

    Google Scholar 

  22. Quigley EMM, Fried M, Gwee K-A, et al. World Gastroenterology Organisation global guidelines irritable bowel syndrome: a global perspective update September 2015. J Clin Gastroenterol. 2016;50(9):704–13.

    Article  PubMed  Google Scholar 

  23. National Institute for Health Care and Excellence. Irritable bowel syndrome in adults: diagnosis and management. Clinical guideline. 2015. https://www.nice.org.uk/. Accessed 23 Mar 2017.

  24. Cash BD. Eluxadoline: a promising therapy that raises many questions. Transl Gastroenterol Hepatol. 2016;1:76.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Buono JL, Carson RT, Flores NM. Health-related quality of life, work productivity, and indirect costs among patients with irritable bowel syndrome with diarrhea. Health Qual Life Outcomes. 2017;15(1):35.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Buono JL, Mathur K, Averitt AJ, et al. Economic burden of inadequate symptom control among US commercially insured patients with irritable bowel syndrome with diarrhea. J Med Econ. 2017;20(4):353–62.

    Article  PubMed  Google Scholar 

  27. McNeil Products Ltd. Imodium original 2 mg capsules: summary of product characteristics. 2016. http://www.medicines.org.uk/emc/medicine/23101. Accessed 23 Mar 2017.

  28. Afghani E, Lo SK, Covington PS, et al. Sphincter of Oddi function and risk factors for dysfunction. Front Nutr. 2017. doi:10.3389/fnut.2017.00001.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

During the peer review process, the manufacturer of eluxadoline was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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  1. Springer, Private Bag 65901, Mairangi Bay 0754, Auckland, New Zealand

    Gillian M. Keating

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  1. Gillian M. Keating
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Correspondence to Gillian M. Keating.

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The preparation of this review was not supported by any external funding.

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Gillian Keating is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: B.D. Cash, University of Southern Alabama, Gastroenterology Division, Mobile, AL, USA; F. Mearin, Centro Médico Teknon, Institute of Functional and Motor Digestive Disorders, Barcelona, Spain; E. Rey, Hospital Clínico San Carlos, Division of Digestive Diseases, Universidad Complutense, Madrid, Spain; L.R. Schiller, Baylor University Medical Center, Division of Gastroenterology, Dallas, TX, USA.

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Keating, G.M. Eluxadoline: A Review in Diarrhoea-Predominant Irritable Bowel Syndrome. Drugs 77, 1009–1016 (2017). https://doi.org/10.1007/s40265-017-0756-7

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