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Background

Managing IBS patients Dr Sameer Zar MBBS FRCP PhD Consultant Gastroenterologist Epsom & St Helier NHS Trust. Background. IBS affects 17 - 25% of general population Approx. 50% IBS patients seek health care (predictors are age, female gender, abdominal pain, psychological distress)

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Background

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  1. Managing IBS patients Dr Sameer ZarMBBS FRCP PhDConsultant GastroenterologistEpsom & St Helier NHS Trust

  2. Background • IBS affects 17 - 25% of general population • Approx. 50% IBS patients seek health care (predictors are age, female gender, abdominal pain, psychological distress) • IBS accounts for 30 – 50% referrals to gastroenterology clinics • Controversy whether IBS is a distinct disease entity or represents several different disease processes

  3. 98% no change in diagnosis 88% have symptoms n=398 2-32 Years median ? years n=5952 1-8 years IBS - Prognosis

  4. Genetics - IBS clusters in families OR 2.72, 95% CI 1.19-6.25 Pts relatives Spouses relatives Kalanatar et al. Gut 2003; 52: 1703-7

  5. Pathophysiological model of IBS • Psychosocial Factors • Life stress • Psychological state • Coping • Social support • Genetics • Environment • Bacterial Flora • Food Hypersensitivity • Outcome • Medication • Surgery visits • Daily function • QoL • IBS • Symptom experience • Behaviour CNS ENS • Physiology • Motility • Sensation Drossman DA et al, Gastroenterology 2002, 123:2108-2131

  6. Diagnosis of IBS - Rome III Criteria Recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months associated with 2 or more: Onset associated with change in frequency of stool Onset associated with change in form (appearance) of stool Improvement with defecation and/or and/or Criteria fulfilled for the last 3 months with symptoms onset at least 6 months prior to diagnosis Longstreth G., Gastroenterology 2006

  7. Physical Examination Full blood count ESR Stool testing Occult blood O & P M, C & S Sigmoidoscopy/ Colonoscopy IBS Diagnosis Initial Evaluation Rome Recommendations • Additional studies if needed

  8. Is screening for coeliac disease justified in IBS patients? IgA TTG positive True positive 11 False positive 1 Ig TTG negative but IgG or IgA AGA positive True positive 3 False positive 51 Sanders et al. Lancet 2001

  9. Graded Treatment Response Symptom severity Severe Moderate Mild

  10. Treatment Approach Effective Physician-Patient Interaction Attentive listening/Silence How long does a patient talk when asked an open question? How soon is the patient interrupted before he completes talking?

  11. IBS Physician Patient Relationship Guidelines • Identify concerns • Explain basis for symptoms • Reassure • Cost effective evaluation • Involve patient • Provide Continuity • Set realistic limits Drossman at al, Gastroenterology 1992;116;1008 Owens et al Annals of Int Med;1995:122;107

  12. Treatment Approach • Effective Physician-Patient Interaction • Symptom Pattern • Diarrhoea Predominant • Constipation Predominant • Mixed/Alternating

  13. Long Transit (e.g. 100 hrs) Short Transit (e.g. 10 hrs)

  14. 100 75 50 25 0 % BM Hard or Lumpy IBS-C IBS-M Type 1,2 . IBS-U IBS-D Types 6,7 0 25 50 75 100 % BM Loose or watery Rome III IBS Subtypes 25% of BM is the threshold for classification

  15. Available IBS Treatments Bloating Tegaserod Probiotics ?Antibiotics ?Exclusion diet Defecatory disorder Abdominal Pain / discomfort Abdominal Pain Anticholinergics Antidepressants Alosetron (IBS-D) Tegaserod (IBS-C) Altered bowel function Diarrhoea Anticholinergics Loperamide/Diphenoxylate Probiotics Clonidine Cholestyramine Alosetron Constipation Fibre Osmotic laxatives (Movicol) Tegaserod /Prucalapride Lubiprostone Biofeedback (Dyssynergia) Surgery (Colonic Inertia)

  16. IBS with Constipation (IBS-C)

  17. Efficacy of Fibre in IBS • Evidence for Ispaghula • 6 studies, 321 patients • Significant effect on overall IBS symptoms • RR = 0.78; 95% CI = 0.63 to 0.96 • NNT = 6 (95% CI = 3 to 50) • Recommendation • Bran has not been shown to be useful in IBS • Use in mild-moderate IBS • More effective in IBS-C • May need to start with lower dose (e.g. 1 tsp/day) and then increase as needed and tolerated Ford AC et al. BMJ 2008; 337;a2313

  18. Lubiprostone in IBS-C • Efficacy in clinical trials • Significantly higher overall response vs. placebo1 • Grade 1B2 • What actually helps • Start at 8μg bid • Can increase to 24μg bid if needed • Take with meals to reduce nausea Pts achieving response (%) 1 Drossman DA, et al. Gastroenterology. 2007;132;2586-2587 2 ACG IBS Task Force, AM J Gastro 2009; 104 (S1); S1-S35

  19. Long-Term Effectiveness of PEG in Chronic Constipation % of patients Dipalma JA et al. Am J Gastroenterol. 2007

  20. Laxatives in IBS • Polyethylene glycol (PEG) • Improved stool frequency but not abdominal pain in IBS-C • Laxatives help constipation symptoms • Partially help bloating and pain/discomfort • Overuse can worsen symptoms ACG IBS Task Force, Am J Gastro 2009

  21. Prucalopride in IBS • Stimulates colonic activity and transit (5HT-4 receptor) • Dose 2mg od (age <65yrs) & 1mg od (age>65) • Women with chronic constipation • Failed treatment at least two other types of laxatives and lifestyle changes for 6 months • SE: abdominal pain, nausea, headache & diarrhoea • Increase in bowel movements to 3 or more per week (Prucalopride 30% vs. placebo 11%, p<0.001 Nice Guidelines 2011

  22. IBS with Diarrhoea (IBS-D)

  23. Loperamide for IBS-D • Efficacy in clinical trials • Not more effective than placebo at reducing pan, bloating, or global symptoms of IBS, but it is effective for the treatment of diarrhoea, reducing stool frequency, and improving stool consistency (Grade 2C) • What actually helps • Use prn for episodic diarrhoea • Use proactively • Start with low dose to avoid constipation • Can use up to 2 tablets qid for more severe diarrhoea ACG IBS Task Force, Am J Gastro 2009

  24. 5HT3 Antagonists: Alosetron • Clinical trial results1 • 8 studies, 4987 patients • RR symptom remain = 0.79 (95% CI 0.69 to 0.90) • NNT = 8 (95% CI = 5 to 17) • Indication – women with severe IBS-D • What really helps • Start with 0.5mg bid • Teach patient to titrate dose to avoid constipation and relieve pain and diarrhoea • Monitor for constipation and ischemic colitis 1Ford AC et al. Am J Gastroenterol 2009

  25. Other medications for IBS-D • Antispasmodics • Tricyclic antidepressants • Rifaximin

  26. Abdominal Bloating in IBS

  27. Assess Factors Contributing to Bloating and Gas in IBS • What goes in • Diet history and relationship to symptoms; food and symptom diary • Assess lactose and fructose intolerance • FODMAPs diet1 • What goes out • Slowed transit and altered gas handling • Need to treat constipation • What they feel • Increased visceral perception 1Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols; includes fructose, fructans, raffinose, polyols 1Shepherd et al. Clin Gastroenterol Hep 2008

  28. Overall Improvement of IBS with Rifaximin10 Weeks Follow-up Pimentel M, et al. Ann Intern Med. 1006:145;557

  29. Rifaximin in IBS • Patient selection: mild-moderate severity, bloating and gas, IBS-D and IBS-M • Breath tests may not predict treatment response • Use at least 1200mg/day x 10 days • Lack of data on lengthening duration of response and repeated treatment ACG IBS Task Force, Am J Gastro 2009

  30. IBS – Luminal Microbial Environment Injurious Pro-inflammatory Bacteroides vulgatus Enterococcus faecalis E. coli (enteroadherent/ invasive) Protective Probiotics Lactobacilliyus sp. Bifidobacterium sp. Non-pathogenic E. coli Mild toSevere IBS

  31. Probiotics • Evidence • 18 trials, 1650 patients1 • RR symptoms remain = 0.71 (95% CI = 0.57 to 0.88) • NNT= 4 (95% CI = 3 to 12.5) • Only probiotic to demonstrate efficacy in appropriately designed RCTs in B infantis 356242 • Recommendation • Patient selection: milder severity, bloating and gas symptoms • Not clear if one is better than other in clinical practice • Lack of quality data on available probiotics 1Moayyedi P et al. Gut, Dec 2008 2Brenner DM et al. Am J Gastroenterol. 2009

  32. Selection of Patients for Antibacterial Therapy in IBS Does patient fit clinical profile of bacterial overgrowth: Postprandial abdominal discomfort, bloating and loose stools ? H2 Breath Test Antibiotic Maintenance with a probiotic Stool normalises or constipation Consider prokinetic to accelerate small bowel transit Symptoms recur, previous test + Repeat breath study, treat only if positive or Sustained response (>6months)

  33. Food Hypersensitivity in IBS • 20 – 65% of IBS patients attribute symptoms to adverse food reactions • Estimated prevalence of food hypersensitivity is 1.4 – 1.8% in general population Young et al, Lancet 1994; 343: 1127-30 • Exclusion diets may be beneficial in IBS patients

  34. Exclusion Diets in IBS

  35. Food specific IgG4 antibodies in IBS Zar et al, AJG 2005

  36. Effect of exclusion diet in IBS Zar et al. Scand J Gastroenterol 2005; 40(7): 800-7

  37. IgG4 guided exclusion diet in IBS 10 lost to f/up 9 lost to f/up Atkinson et al, Gut 2004; 53: 1459-1464

  38. Abdominal Pain in IBS

  39. Antispasmodics in IBS • Evidence • 22 studies; 12 antispasmodics; 1778 patients • Overall symptoms improvement vs. placebo: 61% vs. 44% • RR symptoms remain = o.68 (95% CI = 0.57 to 0.81) • NNT = 5 (95 % CI = 4 to 9) • Recommendation • Use in patients with intermittent symptoms • Can help decrease post-prandial pain • Use proactively, i.e. 30 min before meals • Chronic use can cause constipation, dry mouth, ?loss of response Ford AC et al. BMJ 2008

  40. Rationale for Antidepressants • Peripheral effects • Motility / secretion • Afferent • Central pain modulatory effects • Treatment of psychiatric co-morbidity (in higher doses) Moderate toSevere IBS-D

  41. Rationale for Antidepressants Talk about these as ‘central pain modulators’ rather than antidepressants Moderate toSevere IBS-D

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