The impact of treatment with eluxadoline on health-related quality of life among adult patients with irritable bowel syndrome with diarrhea

Jessica L Abel, Robyn T Carson, David A Andrae, Jessica L Abel, Robyn T Carson, David A Andrae

Abstract

Purpose: Irritable bowel syndrome with diarrhea (IBS-D) significantly impacts health-related quality of life (HRQOL). This post hoc analysis of two phase III trials evaluated the effects of eluxadoline treatment on disease-specific HRQOL among patients with IBS-D.

Methods: Adult patients meeting Rome III criteria for IBS-D were randomized to oral eluxadoline (75 mg or 100 mg) or placebo twice daily in two phase III clinical trials for 52 weeks (IBS-3001) and 26 weeks (IBS-3002). The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire assessed disease-specific HRQOL throughout the study. Changes from baseline to Week 26 in IBS-QOL total and subscale scores were analyzed using an analysis of covariance model. Percentages of IBS-QOL responders with ≥ 14- and 20-point changes were evaluated for IBS-QOL total and subscale scores. A longitudinal mixed-effects model was fitted to evaluate mean IBS-QOL total scores. A cumulative distribution function for change from baseline to Week 26 in IBS-QOL total score was plotted.

Results: Mean changes from baseline to Week 26 for the IBS-QOL total and all subscale scores were significantly higher for patients treated with eluxadoline (both doses) compared to placebo. A significantly greater proportion of eluxadoline-treated patients were responders compared to placebo. Mean and mixed-effects model estimated mean IBS-QOL total scores were consistently higher for eluxadoline versus placebo over 52 weeks.

Conclusions: Compared to placebo, twice-daily eluxadoline treatment significantly improved HRQOL among patients with IBS-D in two phase III trials.

Keywords: Diarrhea; Eluxadoline; Health-related quality of life; IBS-QOL; Irritable bowel syndrome.

Conflict of interest statement

Conflict of interest

JLA and RTC are employees of Allergan plc and own stock and stock options. DAA is a former employee of Allergan plc and owns stock.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Mean IBS-QOL total and subscale scores at baseline and Week 26 for the eluxadoline 75 mg and 100 mg treatment groups versus placebo. Mean differences were calculated for each treatment group, and comparisons were made between the different treatment groups. IBS-QOL Irritable Bowel Syndrome Quality of Life questionnaire. *p ≤ 0.05, **p < 0.01, ***p < 0.001 versus placebo, analysis of covariance
Fig. 2
Fig. 2
Longitudinal data on a mean IBS-QOL total scores and b mixed-effects model estimated means with 95% confidence intervals for the eluxadoline 75 mg and 100 mg treatment groups versus placebo. Data pooled from IBS-3001 and IBS-3002 for all time points up to Week 26; Weeks 36–52, IBS-3001 only. IBS-QOL Irritable Bowel Syndrome Quality of Life questionnaire
Fig. 3
Fig. 3
Cumulative distribution function plots of changes from baseline to Week 26 for IBS-QOL total scores for the eluxadoline 75 mg and 100 mg treatment groups versus placebo. IBS-QOL Irritable Bowel Syndrome Quality of Life questionnaire

References

    1. Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: A clinical review. Journal of the American Medical Association. 2015;313(9):949–958. doi: 10.1001/jama.2015.0954.
    1. Lacy BE, Mearin F, Chang L, Chey WD, Lembo AJ, Simren M, Spiller R. Bowel disorders. Gastroenterology. 2016;150(6):1393–1407. doi: 10.1053/j.gastro.2016.02.031.
    1. Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clinical Epidemiology. 2014;6:71–80.
    1. Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: A meta-analysis. Clinical Gastroenterology and Hepatology. 2012;10(7):712–721. doi: 10.1016/j.cgh.2012.02.029.
    1. Su AM, Shih W, Presson AP, Chang L. Characterization of symptoms in irritable bowel syndrome with mixed bowel habit pattern. Neurogastroenterology and Motility. 2014;26(1):36–45. doi: 10.1111/nmo.12220.
    1. Spiller R, Aziz Q, Creed F, Emmanuel A, Houghton L, Hungin P, Jones R, Kumar D, Rubin G, Trudgill N, Whorwell P. Guidelines on the irritable bowel syndrome: Mechanisms and practical management. Gut. 2007;56(12):1770–1798. doi: 10.1136/gut.2007.119446.
    1. American Gastroenterological Association. (2015). IBS in America: Survey summary findings. Retrieved November 05, 2016, from .
    1. 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 and Quality of Life Outcomes. 2017;15(1):35. doi: 10.1186/s12955-017-0611-2.
    1. Singh P, Staller K, Barshop K, Dai E, Newman J, Yoon S, Castel S, Kuo B. Patients with irritable bowel syndrome-diarrhea have lower disease-specific quality of life than irritable bowel syndrome-constipation. World Journal of Gastroenterology. 2015;21(26):8103–8109. doi: 10.3748/wjg.v21.i26.8103.
    1. European Medicines Agency. (2016). Truberzi (eluxadoline) EPAR summary for the public. Retrieved February 14, 2018, from .
    1. Wade PR, Palmer JM, McKenney S, Kenigs V, Chevalier K, Moore BA, Mabus JR, Saunders PR, Wallace NH, Schneider CR, Kimball ES, Breslin HJ, He W, Hornby PJ. Modulation of gastrointestinal function by MuDelta, a mixed µ opioid receptor agonist/µ opioid receptor antagonist. British Journal of Pharmacology. 2012;167(5):1111–1125. doi: 10.1111/j.1476-5381.2012.02068.x.
    1. US Food and Drug Administration. (2015). Viberzi (eluxadoline) highlights of prescribing information. Retrieved February 14, 2018, from .
    1. Lembo AJ, Lacy BE, Zuckerman MJ, Schey R, Dove LS, Andrae DA, Davenport JM, McIntyre G, Lopez R, Turner L, Covington PS. Eluxadoline for irritable bowel syndrome with diarrhea. New England Journal of Medicine. 2016;374(3):242–253. doi: 10.1056/NEJMoa1505180.
    1. Chey WD, Dove LS, Andrae DA, Covington PS. Early response predicts a sustained response to eluxadoline in patients with irritable bowel syndrome with diarrhoea in two phase 3 studies. Alimentary Pharmacology and Therapeutics. 2017;45(10):1319–1328. doi: 10.1111/apt.14031.
    1. Cash BD, Lacy BE, Schoenfeld PS, Dove LS, Covington PS. Safety of eluxadoline in patients with irritable bowel syndrome with diarrhea. American Journal of Gastroenterology. 2017;112(2):365–374. doi: 10.1038/ajg.2016.542.
    1. Chang L. Review article: Epidemiology and quality of life in functional gastrointestinal disorders. Alimentary Pharmacology and Therapeutics. 2004;20(Suppl 7):31–39. doi: 10.1111/j.1365-2036.2004.02183.x.
    1. Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006;130(5):1377–1390. doi: 10.1053/j.gastro.2006.03.008.
    1. Patrick DL, Drossman DA, Frederick IO, DiCesare J, Puder KL. Quality of life in persons with irritable bowel syndrome: Development and validation of a new measure. Digestive Diseases and Sciences. 1998;43(2):400–411. doi: 10.1023/A:1018831127942.
    1. Andrae DA, Patrick DL, Drossman DA, Covington PS. Evaluation of the Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire in diarrheal-predominant irritable bowel syndrome patients. Health and Quality of Life Outcomes. 2013;11:208. doi: 10.1186/1477-7525-11-208.
    1. Andrae DA, Covington PS, Patrick DL. Item-level assessment of the irritable bowel syndrome quality of life questionnaire in patients with diarrheal irritable bowel syndrome. Clinical Therapeutics. 2014;36(5):663–679. doi: 10.1016/j.clinthera.2014.04.009.
    1. Drossman D, Morris CB, Hu Y, Toner BB, Diamant N, Whitehead WE, Dalton CB, Leserman J, Patrick DL, Bangdiwala SI. Characterization of health related quality of life (HRQOL) for patients with functional bowel disorder (FBD) and its response to treatment. American Journal of Gastroenterology. 2007;102(7):1442–1453. doi: 10.1111/j.1572-0241.2007.01283.x.
    1. Molenberghs G, Kenward MG. Missing data in clinical studies. Chichester: Wiley; 2007.
    1. El-Serag HB, Olden K, Bjorkman D. Health-related quality of life among persons with irritable bowel syndrome: A systematic review. Alimentary Pharmacology and Therapeutics. 2002;16(6):1171–1185. doi: 10.1046/j.1365-2036.2002.01290.x.
    1. Frank L, Kleinman L, Rentz A, Ciesla G, Kim JJ, Zacker C. Health-related quality of life associated with irritable bowel syndrome: Comparison with other chronic diseases. Clinical Therapeutics. 2002;24(4):675–689. doi: 10.1016/S0149-2918(02)85143-8.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner