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Fukudo S, Okumura T, Inamori M, Okuyama Y, Kanazawa M, Kamiya T, Sato K, Shiotani A, Naito Y, Fujikawa Y, Hokari R, Masaoka T, Fujimoto K, Kaneko H, Torii A, Matsueda K, Miwa H, Enomoto N, Shimosegawa T, Koike K. Evidence-based clinical practice guidelines for irritable bowel syndrome 2020. J Gastroenterol 2021; 56:193-217. [PMID: 33538894 PMCID: PMC7932982 DOI: 10.1007/s00535-020-01746-z] [Citation(s) in RCA: 86] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 10/27/2020] [Indexed: 02/06/2023]
Abstract
Managing irritable bowel syndrome (IBS) has attracted international attention because single-agent therapy rarely relieves bothersome symptoms for all patients. The Japanese Society of Gastroenterology (JSGE) published the first edition of evidence-based clinical practice guidelines for IBS in 2015. Much more evidence has accumulated since then, and new pharmacological agents and non-pharmacological methods have been developed. Here, we report the second edition of the JSGE-IBS guidelines comprising 41 questions including 12 background questions on epidemiology, pathophysiology, and diagnostic criteria, 26 clinical questions on diagnosis and treatment, and 3 questions on future research. For each question, statements with or without recommendations and/or evidence level are given and updated diagnostic and therapeutic algorithms are provided based on new evidence. Algorithms for diagnosis are requisite for patients with chronic abdominal pain or associated symptoms and/or abnormal bowel movement. Colonoscopy is indicated for patients with one or more alarm symptoms/signs, risk factors, and/or abnormal routine examination results. The diagnosis is based on the Rome IV criteria. Step 1 therapy consists of diet therapy, behavioral modification, and gut-targeted pharmacotherapy for 4 weeks. For non-responders, management proceeds to step 2 therapy, which includes a combination of different mechanistic gut-targeted agents and/or psychopharmacological agents and basic psychotherapy for 4 weeks. Step 3 therapy is for non-responders to step 2 and comprises a combination of gut-targeted pharmacotherapy, psychopharmacological treatments, and/or specific psychotherapy. These updated JSGE-IBS guidelines present best practice strategies for IBS patients in Japan and we believe these core strategies can be useful for IBS diagnosis and treatment globally.
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Affiliation(s)
- Shin Fukudo
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.
- Department of Behavioral Medicine Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
| | - Toshikatsu Okumura
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masahiko Inamori
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yusuke Okuyama
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Motoyori Kanazawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takeshi Kamiya
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Ken Sato
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Akiko Shiotani
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yuji Naito
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshiko Fujikawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Ryota Hokari
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tastuhiro Masaoka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazuma Fujimoto
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroshi Kaneko
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Akira Torii
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kei Matsueda
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Irritable Bowel Syndrome", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
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Sørensen J, Schantz Laursen B, Drewes AM, Krarup AL. The Incidence of Sexual Dysfunction in Patients With Irritable Bowel Syndrome. Sex Med 2019; 7:371-383. [PMID: 31604682 PMCID: PMC6963115 DOI: 10.1016/j.esxm.2019.08.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 08/19/2019] [Accepted: 08/22/2019] [Indexed: 02/07/2023] Open
Abstract
Introduction Several studies have suggested that patients with irritable bowel syndrome (IBS) frequently have symptoms of sexual dysfunction. Aim The current study aims to map the current knowledge about the burden of sexual dysfunction in patients with IBS. Methods A literature review was conducted on PubMed and EMBASE using the following search terms or combinations thereof: irritable bowel syndrome; functional colonic disease; sexual function; sexual health; sexual behavior; sexual dysfunction; dyspareunia; erectile dysfunction; quality of life; and questionnaire. Main Outcome Measure Sexual dysfunction. Results 1,273 texts were found, 331 duplicates were removed, and 844 texts were excluded because they did not meet the inclusion criteria, leaving 98 full text articles. These were examined and it was found that 41 fulfilled the criteria. 4 questionnaires were found; Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire, the Irritable Bowel Syndrome – Quality of Life (IBSQOL) questionnaire, the Irritable Bowel Syndrome-36 question (IBS-36) questionnaire, and the Arizona Sexual Experience Scale. Subscores for sexual relations in IBS-QOL ranged from 37.7−100 (11.9) for patients with IBS and 82.2−100 (6.6) for controls. The IBSQOL and IBS-36 subscores for sexual relations ranged from 49.7−90.5 (9) to 3.9−5.4 (0.8) with no healthy controls for comparison. After interventions were implemented, there was an improvement in subscores (the IBS-QOL mean changed to 10.5%, IBSQOL mean changed to 3.8%, and the IBS-36 mean changed to 40%). The study using Arizona Sexual Experience Scale showed that 51% of patients with IBS had sexual dysfunction and also scored lower on the IBSQOL questionnaire. Conclusion The information about sexual dysfunction in patients with IBS is sparse and emerges primarily from quality of life questionnaires. It seems as though patients with IBS have more sexual problems compared to controls, but further investigation regarding the extent and type of sexual dysfunction is needed. Sørensen J, Schantz Laursen B, Drewes AM, et al. The Incidence of Sexual Dysfunction in Patients With Irritable Bowel Syndrome. Sex Med 2019;7:371–383.
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Affiliation(s)
- Jeanette Sørensen
- Centre of Neurogastroenterologic Research, Clinic Medicine, The North Regional Hospital, Denmark; Department of Clinical Medicine, Aalborg University, Denmark; Centre for Clinical Research, The North Regional Hospital, Denmark
| | - Birgitte Schantz Laursen
- Sexological Research Centre, Department of Clinical Medicine, Aalborg University, Denmark; Clinical Nursing Research Unit, Aalborg University Hospital, Denmark
| | - Asbjørn Mohr Drewes
- Department of Clinical Medicine, Aalborg University, Denmark; MechSense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark
| | - Anne Lund Krarup
- Centre of Neurogastroenterologic Research, Clinic Medicine, The North Regional Hospital, Denmark; Department of Clinical Medicine, Aalborg University, Denmark; MechSense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark.
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Olden KW, Chey WD, Shringarpure R, Paul Nicandro J, Chuang E, Earnest DL. Alosetron versus traditional pharmacotherapy in clinical practice: effects on resource use, health-related quality of life, safety and symptom improvement in women with severe diarrhea-predominant irritable bowel syndrome. Curr Med Res Opin 2019; 35:461-472. [PMID: 30293448 DOI: 10.1080/03007995.2018.1533456] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Severe diarrhea-predominant irritable bowel syndrome (IBS-D) is associated with decreased health-related quality of life (HRQOL) and increased health care costs. Treatment recommendations for IBS-D often start with traditional pharmacotherapy (TP), with escalation to alosetron, rifaximin or eluxadoline if there is no success. There has been no previous head-to-head clinical trial comparing IBS-D treatment outcome for alosetron versus TP. This study, GSK protocol S3B30020, evaluated resource use, work productivity, health-related quality of life and global symptom response in women with IBS-D who were treated with alosetron or TP. METHODS A total of 1956 patients who met criteria for severe IBS-D were randomized to treatment with alosetron 1 mg twice daily (BID) or only TP for up to 24 weeks. Work productivity and resource use were evaluated by standard questionnaires, HRQOL by the IBSQOL instrument and IBS symptoms by the Global Improvement Scale (GIS). RESULTS Compared to only TP, alosetron-treated patients reported: (1) fewer clinic/office visits for any health problem (p = .0181) or for IBS-D (p = .0004); (2) reduced use of over-the-counter medications for IBS-D (p < .0001); (3) fewer days of lost work productivity (p < .0001); (4) decreased restriction of social and outdoor activities (p < .0001); and (5) greater global improvement in IBS-D symptoms (p < .0001). Alosetron treatment improved HRQOL scores for all domains (p < .0001). Incidence of adverse events during alosetron use was not remarkable and was similar to that previously reported. CONCLUSIONS Alosetron 1 mg BID significantly reduced health care utilization and lost productivity, and significantly improved global IBS symptoms, HRQOL, and participation in outdoor and social activities compared with treatment response to TP.
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Affiliation(s)
- Kevin W Olden
- a Department of Medicine , St Joseph's Hospital and Medical Center , Phoenix , AZ , USA
| | - William D Chey
- b Division of Gastroenterology , University of Michigan Health System , Ann Arbor , MI , USA
| | | | | | - Emil Chuang
- c Prometheus Laboratories Inc. , San Diego , CA , USA
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Effect of heat-sensitive moxibustion plus psychological intervention on SP, 5-HT and quality of life in patients with irritable bowel syndrome. JOURNAL OF ACUPUNCTURE AND TUINA SCIENCE 2017. [DOI: 10.1007/s11726-017-1039-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Cash BD, Pimentel M, Rao SSC, Weinstock L, Chang L, Heimanson Z, Lembo A. Repeat treatment with rifaximin improves irritable bowel syndrome-related quality of life: a secondary analysis of a randomized, double-blind, placebo-controlled trial. Therap Adv Gastroenterol 2017; 10:689-699. [PMID: 28932270 PMCID: PMC5598815 DOI: 10.1177/1756283x17726087] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 07/05/2017] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Diarrhea-predominant irritable bowel syndrome (IBS-D) impairs patient quality of life (QOL). Rifaximin is an oral, nonsystemic antibiotic indicated for IBS-D. The objective of this secondary analysis was to evaluate rifaximin retreatment on IBS-related QOL in patients with IBS-D. METHODS Patients received open-label rifaximin 550 mg three times daily for 2 weeks. Clinical responders [simultaneously meeting weekly response criteria for abdominal pain (⩾30% improvement from baseline in mean weekly pain score) and stool consistency (⩾50% decrease from baseline in number of days/week with Bristol Stool Scale (BSS) type 6 or 7 stools) during ⩾2 of first 4 weeks posttreatment] who relapsed during an up to 18-week treatment-free observation phase were randomly assigned to receive two 2-week courses of double-blind rifaximin or placebo, separated by 10 weeks. A validated 34-item IBS-QOL questionnaire examined patient responses in 8 domains. RESULTS The 2579 patients receiving open-label rifaximin experienced a mean improvement from baseline in IBS-QOL overall score of 54.9%. Responders to open-label rifaximin (n = 1074 of 2438 evaluable; 44.1%) had significantly greater improvement from baseline in IBS-QOL overall and all eight subdomain scores, including dysphoria, food avoidance, interference with activity, body image, and sexual function versus nonresponders at 4 weeks posttreatment (n = 1364; p < 0.001 for all comparisons). A significantly greater percentage of responders to open-label rifaximin achieved the minimally clinically important difference (MCID; ⩾14-point improvement from baseline) in the overall IBS-QOL score versus nonresponders [n = 561 (52.2%) versus n = 287 (21.0%); p < 0.0001]. Among 636 patients with IBS-D relapse, the MCID in the overall IBS-QOL score was achieved by a significantly greater percentage of patients receiving double-blind rifaximin versus placebo (38.6% versus 29.6%, respectively; p = 0.009). CONCLUSIONS Open-label and blinded retreatment with a short course (2 weeks) of rifaximin improved IBS-QOL in patients with IBS-D [ClinicalTrials.gov identifier: NCT01543178].
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Affiliation(s)
- Brooks D. Cash
- University of South Alabama, Digestive Health Center, 75 S. University Blvd, Suite 6000-B, Mobile, AL 36608, USA
| | - Mark Pimentel
- GI Motility Program, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Satish S. C. Rao
- Section of Gastroenterology/Hepatology, Digestive Health Center, Medical College of Georgia Augusta University, Augusta, GA, USA
| | - Leonard Weinstock
- Specialists in Gastroenterology, LLC, Washington University School of Medicine, St Louis, MO, USA
| | - Lin Chang
- Division of Digestive Diseases/Gastroenterology, David Geffen School of Medicine at UCLA, UCLA, Los Angeles, CA, USA
| | | | - Anthony Lembo
- Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
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Boeckxstaens GE, Drug V, Dumitrascu D, Farmer AD, Hammer J, Hausken T, Niesler B, Pohl D, Pojskic L, Polster A, Simren M, Goebel-Stengel M, Van Oudenhove L, Vassallo M, Wensaas KA, Aziz Q, Houghton LA. Phenotyping of subjects for large scale studies on patients with IBS. Neurogastroenterol Motil 2016; 28:1134-1147. [PMID: 27319981 DOI: 10.1111/nmo.12886] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Accepted: 05/17/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. PURPOSE The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu).
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Affiliation(s)
- G E Boeckxstaens
- Translational Research Center for Gastrointestinal Disorders, KULeuven & Department of Gastroenterology and Hepatology, University Hospital Leuven, Leuven, Belgium
| | - V Drug
- Gastroenterology Department, University Hospital "St Spiridon", Gr. T.Popa University of Medicine and Pharmacy, Iasi, Romania
| | - D Dumitrascu
- 2nd Medical Dept., Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - A D Farmer
- Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry, London, UK
- Department of Gastroenterology, University Hospitals of North Midlands, Stoke on Trent, UK
| | - J Hammer
- Medizinische Universität Wien, Universitätsklinik für Innere Medizin 3, Vienna, Austria
| | - T Hausken
- Department of Medicine, Unit of Gastroenterology, Haukeland University Hospital, Bergen, Norway
| | - B Niesler
- Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, Germany
| | - D Pohl
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - L Pojskic
- Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - A Polster
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - M Simren
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - M Goebel-Stengel
- Department of Internal Medicine, Martin-Luther-Krankenhaus, Berlin, Germany
| | - L Van Oudenhove
- Translational Research Center for Gastrointestinal Disorders, KULeuven & Department of Gastroenterology and Hepatology, University Hospital Leuven, Leuven, Belgium
| | - M Vassallo
- Department of Medicine, Mater Dei Hospital, Tal-Qroqq, Malta
| | - K-A Wensaas
- Uni Research Health, Research Unit for General Practice, Bergen, Norway
| | - Q Aziz
- Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry, London, UK
| | - L A Houghton
- Leeds Institute of Biomedical and Clinical Sciences, University of Leeds and Leeds Gastroenterology Institute, Leeds Teaching Hospitals Trust, Leeds, UK
- Centre for Gastrointestinal Sciences, University of Manchester, Manchester, UK
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
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Abstract
OPINION STATEMENT Irritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by abdominal pain and change in bowel habits. IBS diarrhea predominant (IBS-D), which is arguably the most common subset of IBS, is also associated with rectal urgency, increased frequency, abdominal bloating, and loose to watery stools. Current treatments for diarrhea include mu-opioid agonists (i.e., loperamide, lomotil) and bile acid sequestrants (i.e., cholestyramine) while treatments for abdominal pain include antispasmodics (i.e., hyoscyamine, dicyclomine) and tricyclic antidepressants (i.e., amitriptyline). There are currently 3 FDA-approved treatments for IBS-D, which have been shown to improve both abdominal pain and diarrhea. Alosetron was initially approved by FDA 2000; however, its use is now limited to women with severe IBS-D symptoms refractory to other treatment. Eluxadoline, a mixed mu-opioid agonist, and rifaximin, a broad spectrum gut specific antibiotic, were both FDA approved in 2015. Eluxadoline has been shown to relieve abdominal pain and stool consistency in appropriate candidates. While large trials already showed the efficacy of rifaximin in treating non-constipated IBS for bloating, stool consistency, and abdominal pain, the recent TARGET 3 trial demonstrates that retreatment is also effective. While these new treatments significantly expand options for patients suffering from IBS-D, there is likely to remain a need for additional safe and effective therapies.
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Johannesson E, Ringström G, Abrahamsson H, Sadik R. Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects. World J Gastroenterol 2015; 21:600-608. [PMID: 25593485 PMCID: PMC4294172 DOI: 10.3748/wjg.v21.i2.600] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2014] [Revised: 07/29/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the long-term effects of physical activity on irritable bowel syndrome (IBS) symptoms and on quality of life, fatigue, depression and anxiety.
METHODS: Seventy-six patients from a previous randomized controlled interventional study on increased physical activity in IBS were asked to participate in this long-term follow-up study. The included patients attended one visit in which they filled out questionnaires and they underwent a submaximal cycle ergometer test. The primary end point was the change in the IBS Severity Scoring System (IBS-SSS) at baseline, i.e., before the intervention and at follow-up. The secondary endpoints were changes in quality of life, fatigue, depression and anxiety.
RESULTS: A total of 39 [32 women, median age 45 (28-61) years] patients were included in this follow-up. Median follow-up time was 5.2 (range: 3.8-6.2) years. The IBS symptoms were improved compared with baseline [IBS-SSS: 276 (169-360) vs 218 (82-328), P = 0.001]. This was also true for the majority of the dimensions of psychological symptoms such as disease specific quality of life, fatigue, depression and anxiety. The reported time of physical activity during the week before the visit had increased from 3.2 (0.0-10.0) h at baseline to 5.2 (0.0-15.0) h at follow-up, P = 0.019. The most common activities reported were walking, aerobics and cycling. There was no significant difference in the oxygen uptake 31.8 (19.7-45.8) mL per min per kg at baseline vs 34.6 (19.0-54.6) mL/min per kg at follow-up.
CONCLUSION: An intervention to increase physical activity has positive long-term effects on IBS symptoms and psychological symptoms.
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Fukudo S, Kaneko H, Akiho H, Inamori M, Endo Y, Okumura T, Kanazawa M, Kamiya T, Sato K, Chiba T, Furuta K, Yamato S, Arakawa T, Fujiyama Y, Azuma T, Fujimoto K, Mine T, Miura S, Kinoshita Y, Sugano K, Shimosegawa T. Evidence-based clinical practice guidelines for irritable bowel syndrome. J Gastroenterol 2015; 50:11-30. [PMID: 25500976 DOI: 10.1007/s00535-014-1017-0] [Citation(s) in RCA: 92] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Accepted: 11/06/2014] [Indexed: 02/05/2023]
Abstract
New strategies for the care of irritable bowel syndrome (IBS) are developing and several novel treatments have been globally produced. New methods of care should be customized geographically because each country has a specific medical system, life style, eating habit, gut microbiota, genes and so on. Several clinical guidelines for IBS have been proposed and the Japanese Society of Gastroenterology (JSGE) subsequently developed evidence-based clinical practice guidelines for IBS. Sixty-two clinical questions (CQs) comprising 1 definition, 6 epidemiology, 6 pathophysiology, 10 diagnosis, 30 treatment, 4 prognosis, and 5 complications were proposed and statements were made to answer to CQs. A diagnosis algorithm and a three-step treatment was provided for patients with chronic abdominal pain or abdominal discomfort and/or abnormal bowel movement. If more than one alarm symptom/sign, risk factor and/or routine examination is positive, colonoscopy is indicated. If all of them, or the subsequent colonoscopy, are/is negative, Rome III or compatible criteria is applied. After IBS diagnosis, step 1 therapy consisting of diet therapy, behavioral modification and gut-targeted pharmacotherapy is indicated for four weeks. Non-responders to step 1 therapy proceed to the second step that includes psychopharmacological agents and simple psychotherapy for four weeks. In the third step, for patients non-responsive to step 2 therapy, a combination of gut-targeted pharmacotherapy, psychopharmacological treatments and/or specific psychotherapy is/are indicated. Clinical guidelines and consensus for IBS treatment in Japan are well suited for Japanese IBS patients; as such, they may provide useful insight for IBS treatment in other countries around the world.
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Affiliation(s)
- Shin Fukudo
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for irritable bowel syndrome", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13 Ginza, Chuo, Tokyo, 104-0061, Japan,
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Nee J, Zakari M, Lembo AJ. Current and emerging drug options in the treatment of diarrhea predominant irritable bowel syndrome. Expert Opin Pharmacother 2015; 16:2781-92. [PMID: 26558923 DOI: 10.1517/14656566.2015.1101449] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Irritable bowel syndrome diarrhea predominant (IBS-D) is a highly prevalent GI disease, affecting nearly a third of all patients diagnosed with irritable bowel syndrome. Current treatment options are limited. AREAS COVERED This review discusses the pharmacotherapeutic options for IBS-D including currently used medications, the two newly FDA approved medications, as well as emerging therapies with potential benefit in IBS-D. Particular emphasis is placed on rifaximin and eluxadoline and their possible use in IBS-D. EXPERT OPINION Current pharmacological treatment of IBS-D includes loperamide, bile acid sequestrants, antispasmodics, tricyclic antidepressants, alosetron, eluxadoline and rifaximin. The latter two treatments have significantly added to the pharmacotherapeutic options for patients suffering from IBS-D.
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Affiliation(s)
- Judy Nee
- a Harvard Medical School, Beth Israel Deaconess Medical Center , Boston , MA , USA
| | - Mohammed Zakari
- a Harvard Medical School, Beth Israel Deaconess Medical Center , Boston , MA , USA
| | - Anthony J Lembo
- a Harvard Medical School, Beth Israel Deaconess Medical Center , Boston , MA , USA
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Lazaraki G, Chatzimavroudis G, Katsinelos P. Recent advances in pharmacological treatment of irritable bowel syndrome. World J Gastroenterol 2014; 20:8867-8885. [PMID: 25083060 PMCID: PMC4112893 DOI: 10.3748/wjg.v20.i27.8867] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 03/13/2014] [Accepted: 06/23/2014] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a highly prevalent functional disorder that reduces patients’ quality of life. It is a chronic disorder characterized by abdominal pain or discomfort associated with disordered defecation in the absence of identifiable structural or biochemical abnormalities. IBS imposes a significant economic burden to the healthcare system. Alteration in neurohumoral mechanisms and psychological factors, bacterial overgrowth, genetic factors, gut motility, visceral hypersensitivity, and immune system factors are currently believed to influence the pathogenesis of IBS. It is possible that there is an interaction of one or more of these etiologic factors leading to heterogeneous symptoms of IBS. IBS treatment is predicated upon the patient’s most bothersome symptoms. Despite the wide range of medications and the high prevalence of the disease, to date no completely effective remedy is available. This article reviews the literature from January 2008 to July 2013 on the subject of IBS peripherally acting pharmacological treatment. Drugs are categorized according to their administration for IBS-C, IBS-D or abdominal pain predominant IBS.
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Abstract
Irritable bowel syndrome (IBS), characterized by abdominal pain or discomfort associated with a change in bowel patterns, is one of the most common functional gastrointestinal disorders. Because no single drug effectively relieves all IBS symptoms, management relies on dietary and lifestyle modifications, as well as pharmacologic and nonpharmacologic therapies. The authors review current approaches to treatment and discuss nursing implications.
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Cremonini F, Nicandro JP, Atkinson V, Shringarpure R, Chuang E, Lembo A. Randomised clinical trial: alosetron improves quality of life and reduces restriction of daily activities in women with severe diarrhoea-predominant IBS. Aliment Pharmacol Ther 2012; 36:437-48. [PMID: 22779693 PMCID: PMC3464357 DOI: 10.1111/j.1365-2036.2012.05208.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2012] [Revised: 05/21/2012] [Accepted: 06/16/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND Patients with irritable bowel syndrome with diarrhoea (IBS-D) experience restriction in daily activities and decreased health-related quality of life (QOL). AIM To investigate effects of alosetron on patient-reported health-related QOL, satisfaction and productivity in women with severe IBS-D. METHODS A total of 705 women (severe IBS-D, Rome II criteria) randomised to alosetron 0.5 mg QD, 1 mg QD, 1 mg BID, or placebo for 12 weeks were studied. IBSQOL, treatment satisfaction, daily activities, and lost workplace productivity (LWP) were evaluated at randomisation and Week 12. RESULTS One or more doses of alosetron significantly improved all IBSQOL domains except for sexual function from baseline vs. placebo. The magnitude of IBSQOL changes was consistent with a clinically meaningful effect. Alosetron 0.5 mg QD and 1 mg BID significantly reduced IBS interference with social/leisure activities and LWP from baseline vs. placebo [social/leisure (mean ±S.E.) days lost: -6.7 ± 0.8, -7.0 ± 0.9, P < 0.01; LWP (mean ± S.E.) h lost: -11.0 ± 3.3, -21.1 ± 4.1, P < 0.05 respectively]. Significantly more patients treated with alosetron reported satisfaction vs. placebo. Improvements in IBSQOL, LWP, and treatment satisfaction significantly correlated with global improvement of IBS symptoms. The incidence of adverse events with alosetron was low with constipation being the most commonly reported event. A single case of ischaemic colitis occurred, in a patient receiving alosetron 0.5 mg QD. CONCLUSIONS In women with severe IBS-D, alosetron treatment, including 0.5 mg QD, resulted in statistically significant and clinically relevant improvements in health-related QOL, restriction of daily activities and treatment satisfaction over placebo. IBS symptom improvement corresponded with positive changes in IBSQOL, LWP and treatment satisfaction.
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Affiliation(s)
- F Cremonini
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA02215, USA.
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15
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Ringström G, Störsrud S, Simrén M. A comparison of a short nurse-based and a long multidisciplinary version of structured patient education in irritable bowel syndrome. Eur J Gastroenterol Hepatol 2012; 24:950-7. [PMID: 22617366 DOI: 10.1097/meg.0b013e328354f41f] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Structured multidisciplinary patient group education has positive effects on symptoms, health-related quality of life, and disease-related knowledge in patients with irritable bowel syndrome (IBS), but few studies comparing different forms of educational interventions are available. Our aim was to compare the effects of long multidisciplinary group education with a short nurse-based group education with regard to symptoms, knowledge, quality of life, and satisfaction with the intervention in IBS patients. METHODS Patients with IBS according to the Rome II criteria were randomized to either short nurse-based or a long multidisciplinary-based education. The effects were evaluated by self-administered questionnaires at 3, 6, and 12 months after baseline, and compared between the groups. RESULTS No differences in effects were detected in the between-group comparisons at any of the follow-up assessments. However, positive effects on symptoms, knowledge, quality of life, and satisfaction with the intervention were found in both the short and the long version. CONCLUSION A short, nurse-based educational intervention seems to be as efficacious as a longer multidisciplinary version. In both groups, positive effects on patients' well-being were found to a similar extent. This is an important finding that, from a cost-effective perspective, could contribute toward an optimized management of patients with IBS.
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Affiliation(s)
- Gisela Ringström
- Department of Internal Medicine, Section of Gastroenterology & Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden.
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16
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Lucak S. Irritable bowel syndrome and ischemic colitis: evidence supporting the increased use of alosetron. Therap Adv Gastroenterol 2012; 5:215-8. [PMID: 22778787 PMCID: PMC3388526 DOI: 10.1177/1756283x12450934] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Susan Lucak
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, 121 East 69th Street, New York, NY 10021, USA
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17
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Abstract
Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients’ daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1) for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong) 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT3 receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT3 receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized treatment plans for patients with this heterogeneous disorder.
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Affiliation(s)
- Kevin W Olden
- Department of Medicine, St Joseph's Hospital and Medical Center, Phoenix, AZ, USA
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Mangel AW, Hicks GA. Asimadoline and its potential for the treatment of diarrhea-predominant irritable bowel syndrome: a review. Clin Exp Gastroenterol 2012; 5:1-10. [PMID: 22346361 PMCID: PMC3278196 DOI: 10.2147/ceg.s23274] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a multifactorial condition with principal symptoms of pain and altered bowel function. The kappa-opioid agonist asimadoline is being evaluated in Phase III as a potential treatment for IBS. Asimadoline, to date, has shown a good safety profile and the target Phase III population - diarrhea-predominant IBS patients with at least moderate pain - was iteratively determined in a prospective manner from a Phase II dose-ranging study. The clinical data in support of this population are reviewed in this article. Furthermore, the scientific rationale for the use of asimadoline in the treatment of IBS is reviewed. Considering the high patient and societal burdens of IBS, new treatments for IBS represent therapeutic advances.
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Abstract
Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients' daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1) for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong) 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT(3) receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT(3) receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized treatment plans for patients with this heterogeneous disorder.
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Affiliation(s)
- Kevin W Olden
- Department of Medicine, St Joseph's Hospital and Medical Center, Phoenix, AZ, USA
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20
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Practical Considerations for Recognizing and Managing Severe Irritable Bowel Syndrome. Gastroenterol Nurs 2012; 35:12-21; quiz 22-3. [DOI: 10.1097/sga.0b013e31823ff0e8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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Chey WD, Maneerattaporn M, Saad R. Pharmacologic and complementary and alternative medicine therapies for irritable bowel syndrome. Gut Liver 2011; 5:253-66. [PMID: 21927652 PMCID: PMC3166664 DOI: 10.5009/gnl.2011.5.3.253] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2011] [Accepted: 06/25/2011] [Indexed: 12/11/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by episodic abdominal pain or discomfort in association with altered bowel habits (diarrhea and/or constipation). Other gastrointestinal symptoms, such as bloating and flatulence, are also common. A variety of factors are believed to play a role in the development of IBS symptoms, including altered bowel motility, visceral hypersensitivity, psychosocial stressors, altered brain-gut interactions, immune activation/low grade inflammation, alterations in the gut microbiome, and genetic factors. In the absence of biomarkers that can distinguish between IBS subgroups on the basis of pathophysiology, treatment of this condition is predicated upon a patient's most bothersome symptoms. In clinical trials, effective therapies have only offered a therapeutic gain over placebos of 7-15%. Evidence based therapies for the global symptoms of constipation predominant IBS (IBS-C) include lubiprostone and tegaserod; evidence based therapies for the global symptoms of diarrhea predominant IBS (IBS-D) include the probiotic Bifidobacter infantis, the nonabsorbable antibiotic rifaximin, and alosetron. Additionally, there is persuasive evidence to suggest that selected antispasmodics and antidepressants are of benefit for the treatment of abdominal pain in IBS patients. Finally, several emerging therapies with novel mechanisms of action are in development. Complementary and alternative medicine therapies including probiotics, herbal therapies and acupuncture are gaining popularity among IBS sufferers, although concerns regarding manufacturing standards and the paucity of high quality efficacy and safety data remain.
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Affiliation(s)
- William D Chey
- Division of Gastroenterology, University of Michigan Health System, Ann Arbor, MI, USA
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22
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Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol 2011; 106:915-22. [PMID: 21206488 DOI: 10.1038/ajg.2010.480] [Citation(s) in RCA: 213] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Physical activity has been shown to be effective in the treatment of conditions, such as fibromyalgia and depression. Although these conditions are associated with irritable bowel syndrome (IBS), no study has assessed the effect of physical activity on gastrointestinal (GI) symptoms in IBS. The aim was to study the effect of physical activity on symptoms in IBS. METHODS We randomized 102 patients to a physical activity group and a control group. Patients of the physical activity group were instructed by a physiotherapist to increase their physical activity, and those of the control group were instructed to maintain their lifestyle. The primary end point was to assess the change in the IBS Severity Scoring System (IBS-SSS). RESULTS A total of 38 (73.7% women, median age 38.5 (19-65) years) patients in the control group and 37 (75.7% women, median age 36 (18-65) years) patients in the physical activity group completed the study. There was a significant difference in the improvement in the IBS-SSS score between the physical activity group and the control group (-51 (-130 and 49) vs. -5 (-101 and 118), P=0.003). The proportion of patients with increased IBS symptom severity during the study was significantly larger in the control group than in the physical activity group. CONCLUSIONS Increased physical activity improves GI symptoms in IBS. Physically active patients with IBS will face less symptom deterioration compared with physically inactive patients. Physical activity should be used as a primary treatment modality in IBS.
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Saad RJ. Peripherally acting therapies for the treatment of irritable bowel syndrome. Gastroenterol Clin North Am 2011; 40:163-82. [PMID: 21333906 DOI: 10.1016/j.gtc.2010.12.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Gut-acting therapies are common therapies for irritable bowel syndrome (IBS). Most of these peripheral acting agents are primarily targeted at individual symptoms. The evidence supporting the use of these agents in IBS is largely anecdotal. Serotonergic agents and the chloride channel activator lubiprostone have shown efficacy in treating symptoms of IBS. The clinical evidence supporting the use of these agents is based on data from high-quality clinical trials. The use of serotonergic agents for IBS in the United States is limited to the 5-hydroxytryptamine-3 antagonist alosetron in the treatment of women with severe IBS with diarrhea refractory to traditional therapy.
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Affiliation(s)
- Richard J Saad
- Division of Gastroenterology, University of Michigan Health System, 3912 Taubman Center, 1500 East Medical Center Drive, SPC 5362, Ann Arbor, MI 48109, USA.
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Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common gastrointestinal disorder often diagnosed and managed by primary care physicians (PCPs). Despite the high prevalence of IBS, symptom severity is often underappreciated and inadequately managed. The goal of this review is to discern IBS treatment gaps and identify opportunities for improving its management in the primary care setting, as well as describe the most current clinical experience with alosetron, a targeted treatment for severe diarrhea-predominant IBS (IBS-D) in women. SCOPE PubMed was searched for English language articles using combinations of the following key words: 'irritable bowel syndrome,' 'diarrhea-predominant irritable bowel syndrome,' 'diagnosis,' 'guidelines,' 'general practice,' 'primary care,' 'quality of life,' 'burden,' 'prevalence,' 'patient satisfaction,' 'patient survey,' 'severe,' 'severity,' and 'alosetron.' FINDINGS Establishing the diagnosis of IBS in primary care represents a clinical challenge for many healthcare professionals. While many patients seek care for IBS symptoms in the primary care setting, evidence shows that PCPs are often unaware of established diagnostic criteria for IBS. Establishing the severity of IBS is also problematic, given the lack of consensus guidelines defining severe IBS, which in turn complicates treatment decisions. Severe IBS is often inferred after inadequate response to conventional agents; the level of disease impact on quality of life and patient functioning also defines severity. The selective 5-HT(3) antagonist alosetron has been shown to provide improvement across multiple symptom domains, and the incidence of adverse events continues to be low since the implementation of the Prescribing Program for Lotronex. Alosetron is the only agent approved by the US Food and Drug Administration for treatment of severe IBS-D in women. CONCLUSION PCPs often are required to evaluate and treat suspected IBS. The diagnosis and management of IBS in the primary care setting could be optimized through the use of published diagnostic criteria, adequate assessment of symptom severity, and a thorough knowledge of the therapeutic agents that have provided evidence of effectiveness. In the subset of women who suffer from IBS-D, targeted serotonergic therapy with alosetron has been shown to provide symptom relief across multiple domains, including improvement of the patient's quality of life.
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Affiliation(s)
- Scott Bleser
- Bellbrook Medical Center, Inc., Bellbrook, OH 45305-2742, USA.
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25
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Mangel AW, Williams VSL. Asimadoline in the treatment of irritable bowel syndrome. Expert Opin Investig Drugs 2010; 19:1257-64. [DOI: 10.1517/13543784.2010.515209] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Abstract
Patients with irritable bowel syndrome (IBS) account for >$20 billion in direct and indirect costs annually, a large portion of which relates to making the diagnosis. The diagnosis of IBS is challenging because symptoms can vary between patients and overlap with those of other disorders. This review examines the current diagnostic approach in IBS and discusses new tools that may improve diagnostic confidence earlier in the process. The prevalence of organic disease among patients who meet symptom-based criteria for IBS (eg, Rome III) is generally low; therefore, in the absence of "alarm features," the probability for organic disease is very low. Increased public awareness of IBS symptoms and physician awareness of symptom-based criteria for IBS are needed to facilitate earlier diagnosis. Accumulating evidence suggests that fecal and/or serum biomarkers may be helpful in differentiating IBS from non-IBS disorders. These tools may help minimize unnecessary testing and diagnostic delays. As biomarkers are further studied and developed, they are likely to become an integral part of the diagnosis of IBS and reduce the potential for incorrect diagnosis and treatment delays.
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Affiliation(s)
- Albena D Halpert
- Center for Digestive Disorders, Boston University School of Medicine, Boston, MA 02118, USA.
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27
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Structured patient education is superior to written information in the management of patients with irritable bowel syndrome: a randomized controlled study. Eur J Gastroenterol Hepatol 2010; 22:420-8. [PMID: 19923998 DOI: 10.1097/meg.0b013e3283333b61] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Education and reassurance are proposed to be of great importance in the management of patients with irritable bowel syndrome (IBS), but few trials supporting this are available. Our aim was to compare the effects of a structured patient group education (IBS school) versus receiving written information in the form of an IBS guidebook, on knowledge, symptoms, and quality of life in IBS patients. METHODS Patients with IBS according to the Rome II criteria were randomized to participate in the group education or to receive the guidebook. The effects were evaluated by self-administered questionnaires at 3 and 6 months after baseline. RESULTS One hundred and forty-three patients - 71 in the guidebook group and 72 in the IBS school group - completed the study. Compared with the guidebook group, the patients in the education group showed greater reduction in IBS symptom severity and gastrointestinal (GI)-specific anxiety, as well as greater improvement in perceived knowledge of IBS. Several aspects of health-related quality of life were significantly improved after the group education, but not in the group who received the written information. CONCLUSION A structured patient group education is superior to written information to enhance knowledge of IBS, and improve GI symptoms and GI-specific anxiety in IBS patients.
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Lewis JH. Alosetron for severe diarrhea-predominant irritable bowel syndrome: safety and efficacy in perspective. Expert Rev Gastroenterol Hepatol 2010; 4:13-29. [PMID: 20136586 DOI: 10.1586/egh.09.72] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Irritable bowel syndrome affects 5-10% of North Americans, with an estimated one-third having a diarrhea-predominant form. Alosetron hydrochloride (Lotronex) is a serotonin receptor type 3 antagonist approved in early 2000 for use in women with diarrhea-predominant irritable bowel syndrome (IBS-D). Initial use was widespread, but infrequent serious adverse events of ischemic colitis and severe constipation-related complications prompted alosetron's voluntary withdrawal from the US market in November 2000. Unprecedented public request prompted its reintroduction in 2002 under a Risk Management Plan, including a more restricted indication and a Prescribing Program for Lotronex. Despite these measures, the use of alosetron has been very limited since its reintroduction. Possible deterrents to its use include concerns over safety and the possible medical-legal implications raised by the Risk Management Plan. It is also possible that changes in the natural history and/or diagnosis of IBS-D have reduced the target population. Given the unique regulatory history of alosetron, these issues continue to engender controversy. This article profiles these concerns and reviews the pharmacology, clinical efficacy and safety, and post-marketing experience with alosetron. Myths and misconceptions related to alosetron use, or lack thereof, are addressed to provide the reader with the evidence needed to make informed treatment decisions for their female patients with severe IBS-D.
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Affiliation(s)
- James H Lewis
- Division of Gastroenterology, Director of Hepatology, Georgetown University Medical Center, 3800 Reservoir Road, NW Washington, DC 20007, USA.
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29
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Mangel AW, Fehnel SE. Design of treatment trials in irritable bowel syndrome: opioid agonists and atypical benzodiazepine antagonists. Neurogastroenterol Motil 2008; 20:1086-93. [PMID: 18826559 DOI: 10.1111/j.1365-2982.2008.01198.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel function. Few agents are available for the treatment of IBS. Historically, one impediment to the development of agents to treat IBS was lack of a uniform and robust clinical trial design. Studies occurred with different durations of treatment, endpoints and with different target populations. Great advances have been made over the past decade in trial design including: optimal duration of study, mode of data collection, populations to evaluate and identification of endpoints. Using these refinements, it was possible to demonstrate the efficacy of some new agents. These advances are illustrated by a review of trials with kappa opioid agonists and atypical benzodiazepine antagonists, which appear to be promising new classes of treatments for symptoms in IBS.
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Affiliation(s)
- A W Mangel
- RTI Health Solutions, Research Triangle Park, NC 27709, USA.
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Andresen V, Montori VM, Keller J, West CP, Layer P, Camilleri M. Effects of 5-hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol 2008; 6:545-55. [PMID: 18242143 PMCID: PMC2587294 DOI: 10.1016/j.cgh.2007.12.015] [Citation(s) in RCA: 159] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We performed a systematic review and meta-analyses to estimate treatment efficacy and constipation rate of 5-hydroxytryptamine (serotonin) (5-HT(3)) antagonists in patients with nonconstipated (NC) or diarrhea-predominant (D)-irritable bowel syndrome (IBS). METHODS Two reviewers independently searched MEDLINE, EMBASE, and Web of Science (January 1, 1966 to December 15, 2006) for randomized controlled trials of 5-HT(3) antagonists in IBS reporting clinical end points of the IBS symptom complex and safety parameters. Study characteristics, markers of methodologic quality, and outcomes for the intention-to-treat population for each randomized controlled trial were extracted independently. RESULTS We found 14 eligible randomized controlled trials of alosetron (n = 3024) or cilansetron (n = 1116) versus placebo (n = 3043) or mebeverine (n = 304). Random-effects meta-analyses found 5-HT(3) antagonists more effective than the comparators in achieving global improvement in IBS symptoms (pooled relative risk, 1.60; 95% confidence interval [CI], 1.49-1.72; I(2) = 0%) and relief of abdominal pain and discomfort (pooled relative risk, 1.30; 95% CI, 1.22-1.39; I(2) = 22%). Benefit was apparent for both agents, in patients of either sex. These agents were more likely to cause constipation (pooled relative risk, 4.28; 95% CI, 3.28-5.60, I(2) = 65%); there was less constipation with 5-HT(3) antagonists in D-IBS patients than in mixed populations (NC-IBS and D-IBS; relative risk ratio, 0.65; 95% CI, 0.41-0.99). Nine patients (0.2%) using 5-HT(3) antagonists had possible ischemic colitis versus none in control groups. CONCLUSIONS 5-HT(3) antagonists significantly improve symptoms of NC-IBS or D-IBS in men and women. There is an increased risk of constipation with 5-HT(3) antagonists, although the risk is lower in those with D-IBS.
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Affiliation(s)
- Viola Andresen
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Program, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Department of Internal Medicine, Israelitic Hospital, University of Hamburg, Germany
| | - Victor M. Montori
- Knowledge and Encounter Research Unit, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Jutta Keller
- Department of Internal Medicine, Israelitic Hospital, University of Hamburg, Germany
| | - Colin P. West
- Division of General Internal Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Peter Layer
- Department of Internal Medicine, Israelitic Hospital, University of Hamburg, Germany
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Program, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
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Feagan BG, Sandborn WJ, Hass S, Niecko T, White J. Health-related quality of life during natalizumab maintenance therapy for Crohn's disease. Am J Gastroenterol 2007; 102:2737-46. [PMID: 18042106 DOI: 10.1111/j.1572-0241.2007.01508.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES We evaluated the effects of treatment on health-related quality of life (HRQoL) during a randomized controlled trial of natalizumab maintenance therapy (ENACT-2) using both disease-specific and generic measures. METHODS Crohn's disease patients who received natalizumab as induction therapy in ENACT-1 (N=724) and responded (N=339) were re-randomized to ENACT-2 in which they received natalizumab 300 mg (N=168) or placebo (N=171) every 4 wk for 48 additional wk. Outcome measures were the change from baseline on the inflammatory bowel disease questionnaire (IBDQ), the short form-36 (SF-36), the EuroQol-5D (EQ-5D), and a subject global assessment. RESULTS At entry into ENACT-1, scores indicated substantially impaired HRQoL for both the disease-specific and general measures. Natalizumab responders showed clinically meaningful improvement in HRQoL over the course of the ENACT-1 study. During maintenance therapy, IBDQ and SF-36 scale scores of patients who responded to natalizumab induction and were re-randomized to receive the drug in ENACT-2 (N=168) remained stable, while those re-randomized to placebo (N=171) worsened. At week 60, 48 wk after the initiation of maintenance therapy, the mean change from ENACT-1 baseline of all scales of the IBDQ and the SF-36 was significantly higher for those who continued to receive natalizumab (P<0.001 for all scales). The scores of patients who received maintenance natalizumab treatment were not statistically different from those of a cross-section of the U.S. population for 6 of 8 scales of the SF-36. CONCLUSIONS The substantial improvement in HRQoL experienced by patients who responded to natalizumab induction therapy was maintained during an additional 48 wk of maintenance therapy.
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Affiliation(s)
- Brian G Feagan
- Robarts Research Institute, University of Western Ontario, London, Canada
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Guyonnet D, Chassany O, Ducrotte P, Picard C, Mouret M, Mercier CH, Matuchansky C. Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial. Aliment Pharmacol Ther 2007; 26:475-86. [PMID: 17635382 DOI: 10.1111/j.1365-2036.2007.03362.x] [Citation(s) in RCA: 232] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Health-related quality of life (HRQoL) has been rarely evaluated as a primary endpoint in the assessment of the effect of probiotics on the irritable bowel syndrome (IBS). AIM To study the effects of fermented milk containing Bifidobacterium animalis DN-173 010 and yoghurt strains on the IBS in a multicentre, double-blind, controlled trial. METHODS A total of 274 primary care adults with constipation-predominant IBS (Rome II) were randomized to consume for 6 weeks either the test fermented milk or a heat-treated yoghurt (control). HRQoL and digestive symptoms were assessed after 3 and 6 weeks on an intention-to-treat population of 267 subjects. RESULTS The HRQoL discomfort score, the primary endpoint, improved (P < 0.001) in both groups at weeks 3 and 6. The responder rate for the HRQoL discomfort score was higher (65.2 vs. 47.7%, P < 0.005), as was the decrease in bloating score [0.56 +/- (s.d.)1.01 vs. 0.31 +/- 0.87, P = 0.03], at week 3 in the test vs. the control group. In those subjects with <3 stools/week, stool frequency increased (P < 0.001) over 6 weeks in the test vs. control group. CONCLUSIONS This study suggests a beneficial effect of a probiotic food on discomfort HRQoL score and bloating in constipation-predominant IBS, and on stool frequency in subjects with <3 stools/week.
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Affiliation(s)
- D Guyonnet
- Danone Research, Route Départementale 128, 91767 Palaiseau, France.
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Krause R, Ameen V, Gordon SH, West M, Heath AT, Perschy T, Carter EG. A randomized, double-blind, placebo-controlled study to assess efficacy and safety of 0.5 mg and 1 mg alosetron in women with severe diarrhea-predominant IBS. Am J Gastroenterol 2007; 102:1709-19. [PMID: 17509028 DOI: 10.1111/j.1572-0241.2007.01282.x] [Citation(s) in RCA: 83] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Alosetron is indicated for women with chronic, severe diarrhea-predominant IBS (d-IBS) who have not responded adequately to conventional therapy. Constipation is the most common adverse event with alosetron treatment. Multiple dosing regimens were assessed in a randomized, double-blind, placebo-controlled study (S3B30040) to determine efficacy, tolerability, and evaluate constipation rate. METHODS 705 women with severe d-IBS were randomized to placebo, alosetron 0.5 mg once daily, 1 mg once daily, or 1 mg twice daily for 12 wk. The primary end point was the proportion of week 12 responders (patients with moderate or substantial improvement in IBS symptoms) on the 7-point Likert Global Improvement Scale (GIS). Secondary end points were average rate of adequate relief of IBS pain and discomfort, and bowel symptom improvements. RESULTS The proportion of GIS responders at week 12 (primary time point) was significantly greater in all alosetron groups compared with placebo (54/176 [30.7%], 90/177 [50.8%], 84/175 [48%], and 76/177 [42.9%] for placebo, 0.5, 1 mg once daily, and 1 mg twice daily alosetron groups, respectively; P< or = 0.02). Results were similar for the average adequate relief rate (treatment effects > or =12%, P< or = 0.038). Bowel symptoms were improved in all alosetron groups. Constipation was the most common adverse event (9%, 16%, and 19% patients in the 0.5 mg, 1 mg once daily, and 1 mg twice daily groups, respectively). One event of intestinal obstruction and one of ischemic colitis occurred in the 0.5 mg group, and one event of fecal impaction occurred in the 1 mg twice-daily group. All were self-limited and resolved without sequelae. CONCLUSION Alosetron 0.5 mg and 1 mg once daily as well as 1 mg twice daily are effective in providing global improvement in IBS symptoms, adequate relief of IBS pain and discomfort, and improvement in bowel symptoms in women with severe d-IBS. Lower dosing regimens resulted in a decreased constipation rate.
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Mearin F. [Drug treatment of irritable bowel syndrome: an unmet need]. GASTROENTEROLOGIA Y HEPATOLOGIA 2007; 30:130-7. [PMID: 17374325 DOI: 10.1157/13100075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Affiliation(s)
- Fermín Mearin
- Instituto de Trastornos Funcionales y Motores Digestivos, Servicio de Aparato Digestivo, Centro Médico Teknon, Barcelona, España.
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36
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Müller-Lissner S. "My patients are the sickest". Eur J Gastroenterol Hepatol 2006; 18:465-7. [PMID: 16607139 DOI: 10.1097/00042737-200605000-00002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
People with symptoms of the irritable bowel syndrome represent a broad spectrum with respect to severity of symptoms. Only a minority of them seek medical help and thereby become patients. The more severe are the symptoms that are experienced, the lower are the quality of life ratings, but patients will be more prone to participate in enquiries. This makes it very difficult to gain a representative picture of quality of life in irritable bowel syndrome.
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Affiliation(s)
- Stefan Müller-Lissner
- Department of Internal Medicine, Humboldt University, Park-Klinik Weissensee, Schoenstrasse 80, 13086 Berlin, Germany.
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Whitehead WE, Palsson OS, Levy RL, Feld AD, VonKorff M, Turner M. Reports of "satisfactory relief" by IBS patients receiving usual medical care are confounded by baseline symptom severity and do not accurately reflect symptom improvement. Am J Gastroenterol 2006; 101:1057-65. [PMID: 16573774 DOI: 10.1111/j.1572-0241.2006.00535.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Treatment trials for irritable bowel syndrome (IBS) usually define a responder as a patient who reports satisfactory relief or adequate relief of symptoms at the end of the trial. However, these measures have not been adequately validated. AIMS (1) Compare a binary satisfactory relief measure to alternative ways of defining a treatment responder. (2) Determine whether baseline IBS symptom severity or psychological distress influence the sensitivity of these outcome measures. METHODS A total of 350 patients (81% females, average age 50 yr) who had a medical diagnosis of IBS and satisfied Rome II criteria, were recruited from Group Health Cooperative of Puget Sound. At baseline the Irritable Bowel Severity Scale (IBSS) was used to assess symptom severity and to classify patients as mild, moderate, or severe. Psychological distress and IBS-specific quality of life (IBS-QOL) were also assessed. After 6 months treatment with standard medical care, IBSS and IBS-QOL were reassessed, and patients were asked whether they had experienced satisfactory relief and whether they were somewhat or markedly better. RESULTS Initial severity of IBS significantly affected the proportion who reported satisfactory relief (mild, 72%; moderate, 53%; severe, 44%) and the proportion who were somewhat or markedly better (mild, 62%; moderate, 44%; severe, 38%), but did not affect the proportion with a 50% reduction in symptoms (mild, 26%; moderate, 25%; severe, 23%). Although mild patients were the most likely to report satisfactory relief, they showed no average decrease in symptom severity or improvement in IBS-QOL. Conversely, severe patients, who were the least likely to report satisfactory relief, had the largest reductions in IBS symptom severity and the largest improvements in IBS-QOL. Psychological distress had no significant effect on the responder rate after adjusting for IBS symptom severity. CONCLUSIONS These data from a descriptive study suggest that satisfactory relief is confounded with initial IBS symptom severity and is poorly correlated with the amount of symptom improvement. Confirmation of these findings in a clinical trial is needed.
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Affiliation(s)
- William E Whitehead
- Division of Gastroenterology and Hepatology and Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7080, USA
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Irvine EJ, Whitehead WE, Chey WD, Matsueda K, Shaw M, Talley NJ, Veldhuyzen van Zanten SJO. Design of treatment trials for functional gastrointestinal disorders. Gastroenterology 2006; 130:1538-51. [PMID: 16678567 DOI: 10.1053/j.gastro.2005.11.058] [Citation(s) in RCA: 243] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2005] [Accepted: 11/03/2005] [Indexed: 02/07/2023]
Abstract
This document addresses the design of trials to assess the efficacy of new treatments for functional gastrointestinal disorders (FGID), emphasizing trials in irritable bowel syndrome and dyspepsia, because most research has been undertaken in these conditions. The double-blind, randomized, placebo-controlled, parallel group trial remains the preferred design. Randomized withdrawal designs, although encouraged by the European Agency for the Evaluation of Medicinal Products, have the same potential disadvantages as a crossover design, including carryover effects, unmasking (unblinding), and overestimation of the potential benefit for clinical practice. Innovative trial designs that evaluate intermittent (on demand) treatment are likely to become more common in the future. Investigators should include as broad a spectrum of patients as possible and should report recruitment strategies, inclusion/exclusion criteria, and attrition data. The primary analysis should be based on the proportion of patients in each treatment arm who satisfy an a priori treatment responder definition, or a prespecified clinically meaningful change in a patient-reported symptom improvement measure. Such measures of improvement are psychometrically validated subjective global assessments or a change from baseline in a validated symptom severity questionnaire. It is unethical to change the responder definition after a trial begins. Data analysis should address all patients enrolled, using an intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include an analysis of harms data and secondary outcome measures to support or explain the primary outcome. Trials should be registered in a public location, prior to initiation, and should be published even if the results are negative or inconclusive.
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Andrews EB, Eaton SC, Hollis KA, Hopkins JS, Ameen V, Hamm LR, Cook SF, Tennis P, Mangel AW. Prevalence and demographics of irritable bowel syndrome: results from a large web-based survey. Aliment Pharmacol Ther 2005; 22:935-42. [PMID: 16268967 DOI: 10.1111/j.1365-2036.2005.02671.x] [Citation(s) in RCA: 122] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Irritable bowel syndrome is a common gastrointestinal disorder, and its prevalence and demographics have been evaluated by different methodologies with varying results. AIM To evaluate irritable bowel syndrome demographic and prevalence characteristics utilizing a web-enabled panel. METHODS From an existing 150 000-member panel, 31 829 individuals were randomly selected and sent screening questionnaires to evaluate irritable bowel syndrome symptoms. Individuals who agreed to participate and completed the screening questionnaire received a second questionnaire related to a diagnosis of irritable bowel syndrome, a more detailed symptom description, and additional burden of illness data. RESULTS Irritable bowel syndrome prevalence was 7%. Prevalence was higher in women vs. men, unmarried individuals vs. married individuals and unemployed individuals vs. employed individuals. Of those completing the second questionnaire, 51% had seen their physicians for irritable bowel syndrome symptoms in the past year and most had an episode within the past 3 months. During the past year, approximately half of the participants had used a prescription medication, and over 90% had used an over-the-counter medication for irritable bowel syndrome. Participants with irritable bowel syndrome demonstrated quality-of-life reductions relative to norms of the United States population. CONCLUSIONS Web-enabled data collection represents a novel tool for rapidly surveying a large population of individuals with irritable bowel syndrome symptoms.
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Affiliation(s)
- E B Andrews
- RTI Health Solutions, Research Triangle Park, NC 27709, USA
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Coremans G. Cilansetron: a novel, high-affinity 5-HT3receptor antagonist for irritable bowel syndrome with diarrhea predominance. ACTA ACUST UNITED AC 2005. [DOI: 10.2217/14750708.2.4.559] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Abstract
Treatment of irritable bowel syndrome (IBS) remains challenging for patients and practitioners. Current therapeutic choices include antidepressants and psychotherapy, which are thought to target central nervous system triggers of symptoms. Data supporting these treatments are reviewed. Therapeutic agents targeted at receptors in the enteric nervous system have recently been developed to act locally in the gut. Alosetron, an antagonist for serotonin-3 receptors, reduces intestinal motility, secretion, and possibly sensitivity. It is effective for diarrhea predominant IBS, although there are some potentially serious side effects. Tegaserod, a serotonin-4 receptor agonist, is a prokinetic agent that speeds small bowel transit and right colon transit in IBS, reducing symptoms of constipation, pain, and bloating. IBS symptoms are improved with integration of old and new therapies, combined with reassurance, education, and lifestyle adjustments.
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Affiliation(s)
- Howard Mertz
- Department of Medicine, Vanderbilt University, Nashville, TN 37205, USA.
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Nam JH, Alnoah Z, Yenumula SR, Murthy S. Epidemiology, pathogenesis and treatment of irritable bowel syndrome. Expert Opin Ther Pat 2005. [DOI: 10.1517/13543776.13.8.1213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Abstract
The epidemiology and health-related quality of life associated with functional gastrointestinal disorders are reviewed, with particular emphasis on irritable bowel syndrome and functional dyspepsia. The literature supports the significant world-wide prevalence of functional gastrointestinal disorders, including irritable bowel syndrome (IBS), functional dyspepsia and chronic constipation. An increased female prevalence has been demonstrated in most studies in patients with IBS and chronic constipation, but not functional dyspepsia. The female to male ratio appears to be greater in the health care-seeking population than in community populations. However, some differences in the reported general prevalence and gender-related prevalence of functional gastrointestinal disorders may be due to cultural factors and study methodology. A significant health care burden is associated with IBS, with increased out-patient services, abdominal and pelvic surgeries, and gastrointestinal- and non-gastrointestinal-related physician visits and health care costs. Health-related quality of life is impacted significantly in patients with functional gastrointestinal disorders, such as functional dyspepsia and IBS, compared with the general healthy population, as well as patients with other chronic medical conditions, such as gastro-oesophageal reflux disease and asthma. Impaired health-related quality of life has been demonstrated, in particular, in patients with moderate to severe disease seen in referral settings. The health-related quality of life appears to improve in treatment responders, or correlates with symptom improvement, with at least some treatment modalities studied in functional gastrointestinal disorders, but further studies are needed. Predictors of health-related quality of life in patients with functional gastrointestinal disorders include psychosocial factors, such as early adverse life events, and symptoms related to visceral perception, e.g. pain and chronic stress. The presence of extra-intestinal symptoms appears to have a major if not greater impact on health care visits, excess health care costs and health-related quality of life in patients with functional gastrointestinal disorders.
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Affiliation(s)
- L Chang
- Center for Neurovisceral Sciences & Women's Health, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
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Lembo AJ, Olden KW, Ameen VZ, Gordon SL, Heath AT, Carter EG. Effect of alosetron on bowel urgency and global symptoms in women with severe, diarrhea-predominant irritable bowel syndrome: analysis of two controlled trials. Clin Gastroenterol Hepatol 2004; 2:675-82. [PMID: 15290660 DOI: 10.1016/s1542-3565(04)00284-8] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The aim of this study was to assess the effect of alosetron on bowel urgency and irritable bowel syndrome (IBS) global improvement in diarrhea-predominant IBS (D-IBS). METHODS Women with a lack of satisfactory bowel urgency control at least 50% of the time during screening were randomized to receive alosetron 1 mg (n = 246) or placebo (n = 246) twice daily. The primary end point was the percentage of days with satisfactory control of bowel urgency. The response rate for the IBS global improvement scale (GIS) was a secondary end point. GIS responders were patients who recorded either moderate or substantial improvement in IBS symptoms relative to the way they felt before entering the study. Other end points included improvement in stool frequency, stool consistency, and percentage of days with incomplete evacuation. Further analyses were performed on a subset of patients who had at least 10 of 14 days during screening (>/=71% of days) with a lack of satisfactory control of bowel urgency. RESULTS Patients had severe chronic IBS symptoms, and 89% of patients had D-IBS. Alosetron resulted in a greater percentage of days with satisfactory control of urgency compared with placebo (69% vs. 56%, respectively, P < 0.001). Greater percentages of alosetron-treated patients were GIS responders at 4, 8, and 12 weeks compared with placebo (59% vs. 41%, 63% vs. 41%, and 68% vs. 46%, respectively, P < 0.001). Patients with more frequent urgency had similar results. Constipation occurred in 28% and 9% of subjects in the alosetron- and placebo-treated groups, respectively. No cases of ischemic colitis were reported. CONCLUSIONS Alosetron effectively manages bowel urgency and improves global symptoms in women with severe chronic D-IBS.
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Affiliation(s)
- Anthony J Lembo
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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Wang WA, He JQ, Hu PJ, Zeng ZY, Chen W. Impact of psychosocial parameters on quality of life in patients with irritable bowel syndrome. Shijie Huaren Xiaohua Zazhi 2004; 12:1626-1630. [DOI: 10.11569/wcjd.v12.i7.1626] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the impact of psychosocial parameters on the quality of life (QOL) in healthcare seeking patients with irritable bowel syndrome (IBS).
METHODS: QOL and psychosocial parameters in consecutive 41 patients with IBS irritable bowel syndrome (IBS) according to Rome II criteria were measured by questionnaires including IBS-QOL, Pittsburgh sleep quality index (PSQI) and symptom checklist-90 (SCL-90), coping style, social supports, respectively. In the meantime, 37 normal subjects were served as a control group. The relationship between IBS-QOL and psychosocial parameters was investigated by regression analysis.
RESULTS: Compared with normal subjects, all subscales scores of QOL were lower (P < 0.05, respectively), especially in dysphoria, interference with activity, health worry, social reaction, and overall score (P = 0.000, respectively). In addition, IBS patients had more psychiatric symptoms (40.24±4.5, t = 2.63, P = 0.047), and higher scores of depression (0.64±0.24, t = 2.53, P = 0.020) and anxiety (0.67±0.30, t = 2.16, P = 0.016). The score of negative coping (40.79±8.01, P < 0.05), fancying (4.95±2.1, P = 0.001) and withdrawal (4.81±2.1, P = 0.004), as well as subjective supporting (23.92±4.2, P = 0.046) in IBS was higher than that in normal subjects. Among IBS patients, the quality of sleep and daily functions significantly decreased, PSQI and sleep disturbances as well as soporific using was markedly increased. Multiple regression analysis showed poorer quality of life in IBS was related with sleep quality (β = 0.281), negative life event (β = -0.363)and anxiety (β = -0.175).
CONCLUSION: QOL in healthcare seeking patients with IBS is impaired significantly, which is negatively associated with the abnormalities of many of psychosocial parameters.
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Abstract
Sensorimotor disorders of the stomach, small intestine and colon have a limited repertoire of clinical manifestations, and there is the potential for more than one mechanism to lead to symptoms. In many recent clinical trial programs of novel agents in neurogastroenterology, the emphasis has been primarily on symptom assessment of broad groups of patients identified by the Rome criteria. Drugs of potential value have fallen by the wayside with this approach. We propose the current paradigm is partly to blame; physiological testing should provide the basis for identifying more homogeneous populations and therapeutic targets within functional bowel disease, and this applies to the upper and lower gut. Here we summarize the evidence that certain biomarkers can, in a limited fashion, be used to predict the success of an experimental medicine in common disorders of gastrointestinal function, including the irritable bowel syndrome and functional dyspepsia. Although the current evidence is limited and is most convincingly demonstrated with examples of transit measurements (for loperamide, alosetron, tegaserod and piboserod), we perceive this paradigm that studies using validated and responsive biomarkers have an important role to play in drug development.
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Affiliation(s)
- M Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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Thielecke F, Maxion-Bergemann S, Abel F, Gonschior AK. Update in the pharmaceutical therapy of the irritable bowel syndrome. Int J Clin Pract 2004; 58:374-81. [PMID: 15161123 DOI: 10.1111/j.1368-5031.2004.00136.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The therapeutic management of the irritable bowel syndrome (IBS) is ineffective and not satisfying either patients or practitioners. Research in functions of the enteric nervous system and its interaction with the central nervous system is the basis for the development of emerging pharmaceuticals in therapy of the IBS. These pharmaceuticals include agents such as opioid agonists, psychotropic agents and particularly serotonin receptor modulators. These novel pharmaceuticals aim to provide a more comprehensive approach in the therapy of the IBS and will serve both patients and practitioners. So far, the US Food and Drug Administration has approved two agents specifically for the treatment of the IBS, both belonging to the group of serotonin receptor modulators. However, questions remain whether a single therapy is sufficient in the management of IBS because this disease is influenced by biological and psychological as well as cultural and social factors.
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Affiliation(s)
- F Thielecke
- Institute of Medical Outcome Research GmbH, Lörrach, Germany.
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Abstract
Alosetron (Lotronex, GlaxoSmithKline) is a potent and selective 5-HT(3)-receptor antagonist approved by the FDA for the treatment of women with diarrhoea-predominant irritable bowel syndrome (IBS) in whom conventional therapy has failed. Studies involving healthy volunteers and IBS patients have demonstrated a beneficial effect of treatment with alosetron on global IBS symptoms, abdominal pain and discomfort, altered bowel function as well as improvement of quality of life (QOL). Data from animals studies suggest the involvement of 5-HT(3) receptors on intrinsic primary afferent neurons in the mediation of the effect of alosetron on gastrointestinal motility and secretion. While definitive proof of a visceroanalgesic action is not available, an additional central mechanism of action is suggested by findings obtained in animal models, as well as from human brain imaging studies. Alosetron shows a greater effectiveness in women, and the role of genetic factors underlying inter-individual differences in the response to alosetron is currently under investigation. The most frequent adverse event associated with the use of alosetron is constipation and in some rare cases, the development of colonic mucosal ischaemia. In the following review, the most recent reported effects of alosetron on gastrointestinal motility, visceral sensitivity and anxiety, both in terms of preclinical and clinical data will be discussed. The impact of alosetron on QOL in IBS patients and the safety of treatment with alosetron, will also be covered.
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Affiliation(s)
- Emeran A Mayer
- Center for Neurovisceral Sciences & Women's Health, VAGLAHS, Bldg 115/CURE 11301 Wilshire Blvd, Los Angeles, CA 90073, USA.
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Lembo A, Weber HC, Farraye FA. Alosetron in irritable bowel syndrome: strategies for its use in a common gastrointestinal disorder. Drugs 2004; 63:1895-905. [PMID: 12930162 DOI: 10.2165/00003495-200363180-00002] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterised by recurrent abdominal pain and altered bowel habits in the absence of any discernible structural, biochemical and physiological abnormalities. Although there is no specific biological marker for the diagnosis of this disorder, recently developed symptom-based criteria provide the tools necessary to make a diagnosis. The precise underlying pathophysiology of IBS remains unknown. However, disturbances in the brain-gut axis involving the central nervous system and the enteric nervous system have emerged as an underlying concept for IBS. In this regard, conventional treatment has been recognised as unsatisfactory for many patients with IBS and novel, neuroenteric modulatory compounds have been introduced for use by clinicians. Specifically, compounds interacting with the 5-hydroxytryptamine (5-HT, serotonin) receptors of the 5-HT3 and 5-HT4 subtype have been demonstrated of benefit in some patients for the treatment of IBS. In this leading article, we present the current data on the pharmacology, clinical trials, indications and adverse effects of alosetron, a potent and selective 5-HT3 antagonist. As a result of the recognition of serious adverse effects, the indication for alosetron has been restricted and it is now indicated only for women with severe diarrhoea-predominant IBS who have symptoms for at least 6 months and who have failed to respond to conventional therapy. Prescribing restrictions and the risk-management programme implemented as required by the US FDA is reviewed along with a summary of the studies to be performed after reintroduction of alosetron to monitor safety.
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Affiliation(s)
- Anthony Lembo
- Department of Gastroenterology, Beth Israel Deaconess Hospital, Boston, Massachusetts 02215, USA.
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50
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Abstract
Functional gastrointestinal disorders such as the irritable bowel syndrome (IBS) cause substantial morbidity and a high amount of healthcare utilisation. However, no direct mortality can be attributed to functional disorders. Hence, drug treatment of IBS must not only be highly efficient to relieve clinical symptoms but also very safe for the long-term use in humans with such chronic disorders. Alosetron is a potent and highly selective serotonin 5-HT(3 )receptor antagonist that in large randomised controlled clinical trials has been shown to be clinically efficient in female patients with diarrhoea-predominant IBS. The efficacy data along with a low number of serious adverse effects in the preclinical and clinical trials suggested a favourable benefit/risk profile that led to US FDA approval of alosetron in early 2000. However, postmarketing experience has proven that several serious adverse effects, including death, occurred in the treated patient population, which resulted (for a time) in the withdrawal of alosetron from the US market by the producer (GlaxoSmithKline). In the meantime, both public pressure and the proposal of a careful postmarketing surveillance have led the FDA to re-approve alosetron to the US drug market under severe restrictions. These restrictions aim to ensure a safer use of the drug with a more favourable safety profile. Under these restrictions, however, it is not very likely that alosetron will become a major treatment option for many patients, but presumably the continued use of this first selective serotonin antagonist will open an avenue for the development of similar drugs with more favourable benefit/risk profiles in the near future.
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Affiliation(s)
- Viola Andresen
- Department of Medicine, Division of Hepatology and Gastroenterology, University-Medicine Charité, Campus Virchow, Berlin, Germany
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