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      Spotlight on eluxadoline for the treatment of patients with irritable bowel syndrome with diarrhea

      review-article
      Clinical and Experimental Gastroenterology
      Dove Medical Press
      eluxadoline, irritable bowel syndrome, diarrhea, stool consistency, pain

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          Abstract

          Background

          Irritable bowel syndrome with diarrhea (IBS-D) has limited options for treatment currently, including mainly anti-motility medications, antispasmodics, and antidepressants. This review discusses the properties of a new drug, eluxadoline, a gut-targeting mu- and kappa-opioid receptor agonist and a delta-opioid receptor antagonist, and its efficacy and safety in patients with IBS-D.

          Materials and methods

          A systematic review of the literature was undertaken to identify studies that had investigated eluxadoline as a treatment in IBS-D. A narrative review of other information is provided with respect to pharmacological and chemical properties. Where suitable, meta-analysis was performed with a random-effects model to produce a pooled estimate.

          Results

          Eluxadoline showed efficacy improving stool consistency (standardized mean difference [SMD]: −0.29 at 12 weeks, p = 0.0004; −0.46 at 26 weeks, p = 0.0001), global symptoms (SMD: −0.15 at 12 weeks, p = 0.006; −0.14 at 26 weeks, p = 0.02), quality of life (SMD: 0.21 at 12 weeks, p < 0.0001; 0.16 at 26 weeks, p = 0.007), pain (SMD: −0.17 at 12 weeks, p = 0.001; −0.16 at 26 weeks, p = 0.01), and adequate relief (odds ratio [OR]: 1.99 at 12 weeks, p < 0.00001; 1.78 at 26 weeks, p < 0.0001). It also improved IBS severity and other abdominal symptoms such as bloating, discomfort, and risk of urgency and fecal incontinence. Its main side effects included constipation (OR: 3.49, p < 0.00001), vomiting (OR: 3.42, p = 0.0002), abdominal pain (OR: 1.78, p = 0.007), and nausea (OR: 1.42, p = 0.07). The overall quality of trials was satisfactory with the meta-analyses providing largely homogeneous outcomes.

          Conclusion

          Eluxadoline’s place in clinical practice might prove useful since the pharmacological options of IBS-D are limited and eluxadoline showed a positive effect in treating the symptoms of IBS-D.

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          Most cited references43

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          Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis.

          Many cross-sectional surveys have reported the prevalence of irritable bowel syndrome (IBS), but there have been no recent systematic review of data from all studies to determine its global prevalence and risk factors. MEDLINE, EMBASE, and EMBASE Classic were searched (until October 2011) to identify population-based studies that reported the prevalence of IBS in adults (≥15 years old); IBS was defined by using specific symptom-based criteria or questionnaires. The prevalence of IBS was extracted for all studies and based on the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Of the 390 citations evaluated, 81 reported the prevalence of IBS in 80 separate study populations containing 260,960 subjects. Pooled prevalence in all studies was 11.2% (95% CI, 9.8%-12.8%). The prevalence varied according to country (from 1.1% to 45.0%) and criteria used to define IBS. The greatest prevalence values were calculated when ≥3 Manning criteria were used (14%; 95% CI, 10.0%-17.0%); by using the Rome I and Rome II criteria, prevalence values were 8.8% (95% CI, 6.8%-11.2%) and 9.4% (95% CI, 7.8%-11.1%), respectively. The prevalence was higher for women than men (OR, 1.67; 95% CI, 1.53-1.82) and lower for individuals older than 50 years, compared with those younger than 50 (OR, 0.75; 95% CI, 0.62-0.92). There was no effect of socioeconomic status, but only 4 studies reported these data. The prevalence of IBS varies among countries, as well as criteria used to define its presence. Women are at slightly higher risk for IBS than men. The effects of socioeconomic status have not been well described. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
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            The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress.

            The clinical assessment and investigation of irritable bowel syndrome would be greatly facilitated by the introduction of a simple, easy to use severity scoring system. Such a system, developed in our department over a number of years, has been submitted to validation in a total of 141 patients and 40 healthy controls. The system, incorporating pain, distension, bowel dysfunction and quality of life/global well-being, was assessed for its ability to reliably score patients previously classified as mild, moderate or severe. The reproducibility and sensitivity to change of the system was also assessed. The maximum achievable score was 500. Mild, moderate and severe cases were indicated by scores of 75 to 175, 175 to 300 and > 300 respectively. Controls scored below 75 and patients scoring in this range can be considered to be in remission. There was a highly significant difference between controls and patients as a whole (P = 0.0001) as well as significant differences (P < 0.01) between all severity categories. Scores repeated within 24 h were very reproducible and sensitivity to change was also extremely good (P < 0.001) with a change of 50 reliably indicating improvement. These results suggest that this scoring system should prove to be a valuable instrument in helping to meet the many challenges offered by irritable bowel syndrome.
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              • Article: not found

              Quality of life in persons with irritable bowel syndrome: development and validation of a new measure.

              How irritable bowel syndrome (IBS) and its treatment affect quality of life (QOL) is important. To develop a quality-of-life measure specific to irritable bowel syndrome, items were generated using a conceptual model and qualitative interviews with persons diagnosed using the Rome criteria. Symptom frequency and bothersomeness indices were created. Psychometric evaluation methods involved an initial cross-sectional survey followed by a repeat survey. The resulting 34-item measure demonstrated high internal consistency (Cronbach's alpha = 0.95) and high reproducibility (ICC = 0.86) with average time of seven days (SD = 1). For discriminant validity: number of symptoms (P < 0.05), self-reported severity of symptoms (P < 0.001), and the functional bowel disorder severity index (P < 0.001) significantly predicted IBS-QOL scores. Convergent validity and analyses confirmed predictions that scores are more closely related to psychological well-being (0.45) than to function (0.36). We conclude this measure meets established psychometric criteria for reliability and validity; testing of its responsiveness is warranted.
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                Author and article information

                Journal
                Clin Exp Gastroenterol
                Clin Exp Gastroenterol
                Clinical and Experimental Gastroenterology
                Clinical and Experimental Gastroenterology
                Dove Medical Press
                1178-7023
                2017
                25 September 2017
                : 10
                : 229-240
                Affiliations
                Gastrointestinal Services, University College London Hospitals, London, UK
                Author notes
                Correspondence: Konstantinos C Fragkos, Gastrointestinal Services, University College London Hospitals, 250 Euston Road, London NW1 2PG, UK, Tel +44 7960 340 489, Email constantinos.frangos.09@ 123456ucl.ac.uk
                Article
                ceg-10-229
                10.2147/CEG.S123621
                5624596
                f8c23a5c-77bb-407c-80b7-2395f02d7383
                © 2017 Fragkos. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Review

                Gastroenterology & Hepatology
                eluxadoline,irritable bowel syndrome,diarrhea,stool consistency,pain
                Gastroenterology & Hepatology
                eluxadoline, irritable bowel syndrome, diarrhea, stool consistency, pain

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