Irritated by the Irritable Bowel Syndrome Does Anything Work?
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1 Irritated by the Irritable Bowel Syndrome Does Anything Work?
2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.
3 Irritable Bowel Syndrome Definition Epidemiology Pathophysiology Presentation Diagnosis Management
4 IBS The Main Message A common problem A chronic and frustrating problem Not a diagnosis of exclusion Consider predominant symptom Consider new therapies Be comfortable and confident in the diagnosis
5 The Irritable Bowel Syndrome. Does Anything Work? Absolutely YES! BUT Only with explanation, patience, and conviction
6 IBS - Terminology Mucous colitis Spastic colitis Nervous bowel Functional bowel disease Irritable bowel syndrome
7 IBS - History Certain painful affections of the intestinal canal. Powell, 1818 Bowels one time constip, at another lax. Cumming, 1849 Membranous enteritis. Da Costa, 1871 Mucous colitis. Osler, 1892 Neurogenic colitis. Bockus, 1928 Irritable colon. Jordan, 1929
8 IBS - Epidemiology Prevalence 15-20% of adults (but only 20% seek medical attention) 12% of primary care visits 25-40% of gastroenterology referrals 9% of adults see physician each year for bowel complaints or abdominal pain.
9 Chronic Diseases in Canada by Age Can J Gastro 2012; 26: 252
10 Prevalence of IBS Worldwide Canada 18% Clin Gastro Hep 2012; 10: 712
11 IBS Health Care Burden IBS No IBS Doctor visits (GI related) Doctor visits (non GI) Days work missed Too sick to work 11.3% 4.2% Health care costs(per yr) $742 $429 Drossman, Dig Dis Sci, 1993 Talley, Gastro, 1995
12 IBS - Definition Continuous or recurrent symptoms for more than 3 months of: 1. Abdominal pain and 2. Disordered defecation Altered stool frequency Altered stool form Altered stool passage Mucous usually with 3. Bloating and distension
13 IBS Non-GI Manifestations Gynecologic Dysmennorrhea, dyspareunia Urologic Dysuria, frequency Musculoskeletal Fibromyalgia Psychologic Depression, anxiety, abuse
14 IBS Subtypes IBS-C Hard or lumpy stools >25% IBS-D Loose or watery stools >25% IBS-M Hard or lumpy stool >25% And loose or watery >25%
15 CIC & IBS-C: What s the Difference? CIC IBS-C Long term ( 6 months) < 3 stools per week Stool form that is mostly hard/lumpy Difficult stool passage (straining and/or incomplete evacuation) Abdominal pain Discomfort associated with abnormal stool frequency/form 15
16 Variable Nature of Symptoms in IBS Am J Gastro 2014; 109: 1450
17 IBS - Pathophysiology Motility disturbance Visceral hypersensitivity Normal perception of abnormal motility, perception of normal motility. or abnormal
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19 Perception of Symptoms Clin Gastro Hep 2014; 12: 2033
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22 IBS The Microbiome Rhee. Nat Rev Gastro Hep 2009; 6: Collins. Nat Rev Gastro Hep 2014; Apr 22, 2014
23 Factors Contributing to Dysbiosis in IBS Nat Rev Gastro Hep 2014; 11: 497
24 Post-Infectious IBS Walkerton, ON 28% at 3yrs 21% at 4yrs 14% at 6yrs 15% at 8yrs Vs 5.4% at 8yrs in well group p< DDW 2009 Abs T2051
25 Relative Risk for Post-Infectious IBS or Functional Dyspepsia APT 2014 doi: /apt.13006
26 IBS-Related Pathways Bases on Genetic Findings Nat Rev Gastro Hep 2016; 13: 77
27 IBS Psychosocial Factors Psychopathology Critical life events Illness behaviour Familial factors
28 Psychiatric Disorders in IBS Compared to Diabetes or Hypertension Current Mood Disorder Current Anxiety Disorder IBS 2.29 ( ) 3.19 ( ) Diabetes 1.18 ( ) 1.41 ( ) Hypertension 1.39 ( ) 1.17 ( ) Mykletun. BMC Gastroent 2010; 10:88
29 Early life Genetics Environment Psychosocial factors Life stress Coping Social support Physiology Motility Sensation IBS Symptom experience Behaviour Outcomes MD visits Medications Daily function Quality of life
30 IBS - Diagnosis Symptom assessment Physical exam Limited screen for organic disease Identify symptom subgroup Constipation predominant Diarrhea predominant Pain, gas, bloating
31 Rome IV Criteria for IBS Diagnosis Recurrent abdominal pain at least 1 day/week (on average) in the last 3 months associated with/related to 2 of the following: Defecation Change in frequency of stool Change in form (appearance of stool) Symptom onset should occur at least 6 months prior to diagnosis and symptoms should be present during the last 3 months Lacy BE, et al. Gastroenterology 2016;150: e5.
32 Differential Diagnosis Diarrhea Infection, inflammation, maldigestion Constipation Obstruction, metabolic Pain Infection, obstruction, inflammation
33 Prevalence of Organic Disease in Patients meeting Criteria for IBS Organic GI disease IBS patients (%) General Pop (%) Colitis/IBD Colorectal Cancer Thyroid dysfunction GI infection NA Celiac sprue Lactose maldigestion Brandt, Am J Gastro 2009: Supp 1
34 IBS Alarm Symptoms New onset over age 50 Significant weight loss GI bleeding Fever Nocturnal bowel movements
35 IBS - Treatment Dialogue Diet Drugs
36 What Patients Know About IBS Misconceptions IBS caused by lack of enzymes 52% IBS is a form of colitis 42.8% IBS will worsen with age 47.9% IBS can develop into colitis 43% IBS can develop into malnutrtion 37.7% IBS can develop into cancer 21.4% Halpert. Am J Gastro 2007; 102: 1972
37 What Patients Want to Know About IBS Foods to avoid 63.3% Causes of IBS 62% Coping strategies 59.4% Medications 55.2% Will they live with it for life 51.6% Halpert. Am J Gastro 2007; 102: 1972
38 Patient Expectations and Their Experience Curr Gastroenterol Rep 2011; 13: 331
39 Patient Expectations and Their Experience Curr Gastroenterol Rep 2011; 13: 331
40 Effect of Physician-Patient Interaction and Number of Return Clinic Visits Owens, Ann Int Med 1995; 122: 107
41 IBS - Treatment Dialogue Diet Drugs
42 Diet Guidelines for IBS Regular meals Taking time to eat Limit high fat foods Good fluid intake with limited fizzy drinks and caffeine Limit sugar-free sweets and sorbitol Limit fruit to 3 portions per day National Institute for Health and Clinical Excellence (NICE) 2008 J Human Nut and Diet 2012; 25: 260
43 Mechanism of Action of Fiber on Intestinal Transit and Visceral Hypersensitivity Am J Gastro 2013; 108: 718
44 IBS Symptom Relief with Fibre BMJ 2009; 339b: 3154
45 Benefit of Psyllium vs Bran in IBS BMJ 2008; 337: a2313
46 Specific Food Avoidances Non-celiac gluten intolerance Lactose intolerance Fructose malabsorption. FODMAP intloerance
47 Gluten Causes GI Symptoms in Subjects Without Celiac Disease A Double Blind Placebo Controlled study Biesiekierski. Am J Gastro 2011; 106: 508
48 FODMAPs Fermentable Oligo, Di and Monosaccharides And Polyols representing: Poorly absorbed and highly fermentable short-chain carbohydrates Results in gas production, increased luminal fluid and distension and peristalsis Eswaran. Gastro Clin NA 2011; 40: 141
49 FODMAPs Fructose Polyols Lactose Fructans and Galactans High FODMAP Apples, pears, honey, fruit juice, dried fruit, corn syrup, watermelon ol sugars, stone fruits, avocado, mushrooms, cauliflower Milk (cow, goat, sheep), yoghurt, soft cheeses Wheat, rye, garlic, onions, artichokes, asparagus, leeks, legumes, lentils, cabbage, sprouts Lower FODMAP Citrus, berries, bananas, grapes, honeydew, cantaloupe, kiwi Glucose, artificial sweeteners not ending in ol (aspartame) Lactose-free dairy, rice milk, hard cheese Rice, corn, potato, quinoa, lettuce, spinach, cucumbers, green beans, bell peppers, tomato, eggplant
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51 Foods containing FODMAPs Fruit Apples Apricots Cherries Pears Watermelon Dried fruit Vegetables Asparagus Broccoli Cabbage Eggplant Garlic Mushrooms Onions Cereals/grains Wheat, rye in large quantities Pasta Bread Cookies Dairy Cow s milk Custard Ice cream Yogurt Soft cheeses Sweeteners Sorbitol Mannitol Isomalt Fructose Corn syrup Honey Beans/legumes Chickpeas Kidney beans Lentils Soybeans Foods suitable for a low FODMAP diet Fruit Bananas Blueberries Grapefruit Lemons Raspberries Vegetables Carrots Celery Green beans Potatoes Pumpkin Zucchini Cereals/grains Gluten-free bread or cereal Rice Oats Polenta Tapioca Dairy Other Lactose-free milk Tofu and yogurt Sugar Hard cheeses Maple syrup Molasses
52
53 Improved Symptoms to Low FODMAP vs Standard IBS Diet Improvement Standard IBS Diet Low FODMAP P Bloating 17/35 32/ Abd pain 20/33 29/ Flatulence 14/28 33/ Diarrhea 18/29 30/ Constipation 10/22 10/ Energy 11/30 20/ Composite Score 19/39 37/43 <0.001 J Hum Nut Dietetics 2011; 24: 487
54 GI Symptom Response to Low FODMAP Diet Gastroenterology 2014; 146: 67
55 Low FODMAPs Same as Traditional Diet Advice Gastro 2015; 149: 1399
56 IBS - Treatment Dialogue Diet Drugs
57 IBS Treatment Drug Therapy Fibre Antidiarrheals Antispasmodics Motility regulators Peppermint oil Choleystyramine Antidepressants Probiotics
58 IBS Treatment Drug Therapy Consider whether Constipation predominant Diarrhea predominant Pain/gas/bloat predominant
59 IBS Current Rx/OTC Treatments Diarrhea Constipation Pain/Bloating Absorbants GI Relaxants Fiber Supplements Osmotic Laxatives Prokinetics GI Stimulants Pro-secretory Anxiolytics Antispasmodics Anti-Gas SSRIs TCAs IBS
60 New Scientist. May14,2011
61 Probiotics Live microorganisms which when given in adequate amounts confer a health benefit on the host 20 RCTs 6 systematic reviews Variable endpoints global symptoms, pain, bloating, flatulence
62 Effect of Probiotics on Global Symptom Scores in IBS Am J Gastro 2014; 109: 1547
63 Bifidobacterium Infantis in Women with IBS (n=362) Am J Gastro 2006; 101: 1581
64 Peppermint Oil 16 clinical trials 9 randomized Small, short, variable endpoints Well tolerated Dose 1-2 capsules tid for 2-4 weeks Phytomed 2005; 12: 601
65 Peppermint Oil in IBS Global Symptom Improvement Am J Gastro 1998; 93: 1131
66 Approaching Antidepressants in IBS Patient expectations You think I m crazy/depressed They are addicting It will alter my mind I tried them and they don t work Discuss mechanism of action Central analgesic, sleep enhancement Lower doses than for depression Not addicting/ can stop
67 Meta-analysis of Tricyclic Antidepressants in IBS NNT 4 Ford. Gut 2009; 58: 367
68 Efficacy Of SSRI s in IBS-C NNT = 2.9 Am J Med 2012; 125: 381
69 Antidepressant Receptor Site Effects Norepinephrine Serotonin Histamine Acetylcholine TCAs Amitryptyline AAntip Doxepin Desipramine Nortriptyline SSRIs Citalopram Escitalopram Fluoxetine Paroxetene Sertraline SNRIs Venlafaxine Duloxetine Neurogast Motil 2015; 27: 455
70 Linaclotide: A Guanylate Cyclase-C (GC-C) Agonist GC-C GC-C is a key regulator of intestinal function (fluid and electrolyte balance) Lumen Guanylin Uroguanylin (endogenous GC-C agonists) Intestinal epithelial cell GC-C is a receptor predominantly expressed on the luminal surface of intestinal epithelial cells Minimally absorbed Negligible systemic bioavailability APT 2014; 39: 371
71 Action of Linaclotide CFTR = Cystic fibrosis transmembrane conductance regulator cgmp = Cyclic guanosine monophosphate GTP = Guanosine triphosphate Brierley SM. Curr Opin Pharmacol 2012;12:632-40
72 % Change Abdominal Pain % Change Ab. Pain Weekly CSBMs Weekly CSBMs Rao S V.1 et al. Am J Gastroenterol, 2012 For intended use only. Do not copy or distribute. 72 Weekly results for abdominal pain and CSBMs Treatment Period p<0.001 for all 12 weeks in the Treatment Period BL p< for all 12 weeks in the Treatment Period Trial Week Trial Trial Week Week RW Period BL Treatment Groups 290 µg linaclotide Placebo
73 Eluxadoline: Mechanism of Action Patients with IBS-D Eluxadoline: experience: Increased Slows GI transit 1 Decreases Increased secretion 2 ReducesVisceral visceral pain Eluxadoline Eluxadoline agonizes binds opioid antagonizes and antagonism receptors opioid opioid in Pain modulates receptors the receptors GI tract fibres agonism Lumen Mucosa Submucosa Dove LS et al. Gastroenterology. 2013;145:329; Fujita W et al. Biochem Pharmacol. 2014;92:448; Wade PR et al. Br J Pharmacol. 2012;167:1111; 73 Viberzi (eluxadoline) [prescribing information]. Parsippany, NJ: Actavis Pharma, Inc., 2016.
74 Daily composite responder rate (%) PRIMARY ENDPOINT AND ADDITIONAL ANALYSIS Composite Response Placebo Eluxadoline 75 mg Eluxadoline 100 mg Pooled IBS-3001 and IBS-3002 data Week Lembo AJ et al. N Engl J Med. 2016;374:242.
75 Sphincter of Oddi Spasm and Pancreatitis Events in Clinical Trials of Eluxadoline Eluxadoline 75 mg (n=807) * Eluxadoline 100 mg (n=1,032) Sphincter of Oddi spasm (SOS) 2 (0.2%) 8 (0.8%) All events resolved upon treatment discontinuation, typically improving by the following day; 80% of cases occurred within 1 week of treatment, and the rest within 1 month. 1 patient had abdominal pain and elevated hepatic enzymes 1 patient had abdominal pain and lipase elevation <3x ULN 7 patients had abdominal pain and elevated hepatic enzymes 1 patient had pancreatitis, occurring within minutes of taking treatment Pancreatitis 2 (0.2%) 3 (0.3%) All pancreatic events resolved with lipase normalization upon treatment discontinuation; 80% of cases resolved within 1 week. 3 patients had excessive alcohol intake 1 patient had biliary sludge 1 patient discontinued treatment prior to symptom onset
76 Muscle Relaxants in IBS Benzodiazepines Librax Pinaverium Trimebutine Hyoscine
77 Sporadic Treatment Antidiarrheals Imodium Choleystyramine Antispasmodic Buscopan Peppermint oil Laxatives
78 Alternative Therapies Herbal Enzymes Antibiotics Psychological Hypnotherapy, psychotherapy, behavioral modification Acupuncture
79 Psychological Therapies in IBS Trials N RR 95% CI NNT 95% CI CBT Relaxation training Dynamic psychotherapy Hypnotherapy Ford. BMJ 2008; 337: a2313
80 Lack of Efficacy of Acupuncture in IBS Am J Gastro 2012; 107: 835
81 New Not yet approved in Canada for IBS Rifaximin Non-absorbable antibiotic Lubiprostone Chloride channel activation Chronic constipation and IBS-C Prucalopride Enterokinetic Chronic idiopathic constipation
82 Global Improvement of IBS Symptoms with Rifaxamin NNT = 10.2 Am J Gastro 2012; 107: 28
83 Improvement of Bloating in IBS with Rifaxamin NNT = 10.1 Am J Gastro 2012; 107: 28
84 Treatment of IBS Number Needed to Treat Spiegel. Clin Gastro Hep 2011; 9: 461
85 Stability of a Diagnosis of IBS Over Time Adapted from Am J Gastro 2001; 96: 2905
86 Survival With IBS Am J Gastro 2010; 105: 822
87 FODMAPs References
88 References Treatment of IBS: beyond fiber and antispasmodics. Ther Adv Gastro 2011; 6: 115 AGA Review on Pharm Management of IBS. Gastro 2014; 147: 1149 Mechanisms and efficacy of FODMAP restriction in IBS. Nat Rev Gastro Hep 2014; 11: 256 Evidence-based dietary management of functional GI symptoms. J Gastr Hep 2010; 25: 252 A gastroenterologist s guide to probiotics. Clin Gastro Hep 2012; 10: 960 Psychological Treatments in FGID: A Primer for Gastros. Clin Gastro Hep 2013; 11: 208 Diagnosis & management of IBS. Nat Rev Gastro Hep 2010; 7: 565 ACG Monograph on Management of IBS. Am J Gastro 2014; 109: S1 IBS: Modern concepts and management. Am J Med 2015; 128: 817
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