IBS current status Peter Laszlo Lakatos

Size: px

Start display at page:

Download "IBS current status Peter Laszlo Lakatos"

Darlene Holmes
6 years ago
Views:

1 IBS current status Peter Laszlo Lakatos Semmelweis University 1st Department of Medicine

2 Functional gastrointestinal disorders Chronic or fluctuating functional gastrointestinal symptoms that can not be explained by structural and/or laboratory changes Camilleri M. Gastroenterology 2001;120:

3 IBS A real and chronic gastrointestinal (GI) disorder of function manifested by a group of symptoms abdominal pain/discomfort bloating/distension constipation and/or diarrhea No known structural or biochemical abnormalities Significantly affects quality of life Need to treat the multiple symptoms of IBS Camilleri M. Gastroenterology 2001;120:652. Thompson et al. Gut 1999;45:43 7

4 Functional gastrointestinal disorders Rome II (1998) Functional oesophageal disorders Functional gastroduodenal disorders Functional bowel disorders Irritable bowel syndrome (IBS) Functional abdominal bloating Functional constipation Functional diarrhoea Unspecified functional bowel disorders Functional biliary disorders Functional anorectal disorders functional pediatric gastrointestinal disorders Drossmann DA Gut 1999;45(SuppIII):II1

5 IBS and Rome The definition matters

6 IBS and bacteria The bacteria hypothesis Lin HC Jama 2004

7 IBS and bacteria - clinical relevance Comparison of rates of positive breath testing in IBS Pimentel Expert Opin. Investig. Drugs 2009

8 The Epidemiology of Irritable Bowel Syndrome (IBS)

9 Worldwide prevalence of IBS US 10 20% Canada 12% Sweden 13% Belgium 8% Denmark 7% UK 22% Netherlands 9% France 20% Germany 12% Spain 13% China 23% Japan 25% Nigeria 30% IBS data not included Australia 12% New Zealand 17% Camilleri et al. Aliment Pharmacol Ther 1997;11:3 15 Drossman. Dig Dis Sci 1993;38: Talley et al. Gastroenterology 1991;101: Müller-Lissner et al. Digestion 2001;64:200 4 Talley. Balliêre s Clin Gastroenterol 1999;13: Thompson et al. Dig Dis Sci 2002;47:225 35

10 Differences between age-groups Age at onset is predominantly at young adulthood In the adolescence: 8-15% In the elderly: in the US in year-olds: 11% in the year-olds: 17% Talley NJ. Gastroenterology 1992;102:895

11 IBS: Diversity in estimates of prevalence Confounding factor Varying definition Diagnosis Population Example Presence of one or more symptoms Manning criteria Rome I or Rome II criteria diagnostic practice Consulters, non-consulters, racial groups, institutional groups, general population

12 Kang YJ Aliment Pharmacol Ther 2005;21:

13 Gender/Ethnical differences Female predominance (2-4:1) Background: Sex hormones, different brain serotonin synthesis Stress and psychological abnormalities Real prevalence is almost the same between man and women, consulter behavior is more common in females Cultural differences: e.g. in India IBS is more prevalent in men De Giorgio R et al. Aliment Pharmacol Ther 2004;20: 10. Talley NJ Ball Clin Gastroenterol 1999;13:371

14 Kang YJ Aliment Pharmacol Ther 2005;21:

15 Health care utilization and QoL in IBS

16 IBS: Consultation pattern Specialists Primary care ~25% consulters ~75% non-consulters ~70% female ~30% male IBS consulters family doctor: 20-25%, specialist: 3-5%

17 IBS: Consultation patterns in the US Mild Severe IBS IBS Physician visits * In-patient stays * Emergency room visits * * over previous 12 months Hahn et al, 1997

18 Cash BD et al. Aliment Pharmacol Ther 2004;19:1235. Koloski NA. Am J Gastroenterol 2001;96:1440 Drossmann DA. Dig Dis Sci 1993;38:1596 Talley NJ. Gastroenterology 1995;109:1736 Health care utilization in IBS Direct costs healthcare consultations Mio visit/year in the US diagnostic tests medications prescriptions/visit in the US preventative measures Absenteeism from work: IBS: 3x as many days from work

19 High surgical rates in IBS cholecystectomy 3x appendectomy and hysterectomy 2x back surgery 1.5x IBS was an independent risk factor Longstreth GF et al. Gastroenterology 2004;126:1665.

20 Cash BD et al. Aliment Pharmacol Ther 2004;19:1235. Koloski NA. Am J Gastroenterol 2001;96:1440 Drossmann DA. Dig Dis Sci 1993;38:1596 Talley NJ. Gastroenterology 1995;109:1736 Health care utilization in IBS COSTS of IBS: ~$ billion in annual direct medical costs in the US ~ $ 41 billion in the 8 most industrialized countries additional ~$10 20 billion in indirect costs, largely resulting from work absenteeism and decreased productivity in the US

21 Annual economic burden of IBS in the US versus other chronic conditions Asthma 1 Migraine 2 Productivity costs IBS 3,4 Hypertensive disease 5 Stroke 5 Arthritis 6 Diabetes Annual costs (billions of US dollars) 1 National Asthma Education and Prevention Program. Asthma statistics, Hu et al. Arch Intern Med 1999;159: American Gastroenterological Association. The Burden of Gastrointestinal Diseases, Martin et al. Am J Manag Care 2001:7(8 Suppl.):S268 S275 5 American Heart Association Heart and Stroke Statistical Update, Praemer et al. Musculoskeletal Conditions in the United States (2nd ed), American Diabetes Association. Diabetes Care 1998;21:

22 Quality of life (HRQOL) HRQOL is lower in patients with gastrointestinal diseases compared to other chronic conditions (e.g. depression, diabetes mellitus or heart failure) It is even lower in functional gastrointestinal diseases (compared to non-functional) Lower in consulters vs non-consulters Oberndorff-Klein Woolthuis et al. Scand J Gastroenterol 2004;39:17 Stewart S. JAMA 1989;262:907 O'Sullivan M. Gastroenterology 1997;112:A801

Mean scale score 90 80 70 60 50 40 30 20 10 0 Relative QoL in IBS (SF-36) Comparison with other diseases US female

23 Mean scale score Relative QoL in IBS (SF-36) Comparison with other diseases US female norms (n=1,412) IBS (n=1,302) IBD (n=546) Congestive heart failure (n=216) Eisen G, 2000; Mayer EM et al, 1999: Ware J, 1993

24 Symptoms of multiple functional disorders may be present Patients with IBS often complain to have symptoms of: Other gastrointestinal (pl. dyspepsia) and/or Non-gastrointestinal (pl. fibromyalgia, noncardiac chest pain, pelvic pain, urogenital problems (dysuria, dysmenorrhea), migrainelike headache, etc.) functional syndromes

25 Pathogenesis of IBS Motility disorder, motor function (1950s) Visceral hypersensitivity (1970s) Brain-gut interaction (1980s) More recent mechanisms: Altered CNS perception of visceral events Psychosocial factors 5-HT (mediated visceral hypersensitivity and gut motility) Genetical, host factors (SERT, IL-10, TGF-b) Others (acute infection/low-grade inflammation, diet, change in the gut-microflora) Barbara G et al. Aliment Pharmacol Ther 2004;20:1-9.

26 The Diagnosis of Irritable Bowel Syndrome (IBS)

27 Diagnostic approach Positive Identify symptom pattern (psychosocial background) Negative Rule out

28 IBS: Manning criteria Four symptoms significantly more common among patients with IBS: looser stools at onset of pain more frequent bowel movements at onset of pain pain eased after bowel movement visible [abdominal] distension Two further symptoms were more common among patients with IBS: passage of mucus feeling of incomplete evacuation Sensitivity: 55-60%, specificity 75-80% Manning et al, Br Med J 1978;2:653-4

29 IBS: Rome II criteria (2000) At least 12 weeks or more, which need not be consecutive, in the preceding 12 months of abdominal discomfort or pain that has two out of three features: (1) Relieved with defecation; and/or (2) Onset associated with a change in frequency of stool; and/or (3) Onset associated with a change in form (appearance) of stool. Thompson WG Gut 1999;45(SuppIII):II43

30 IBS: Rome II criteria (2000) Symptoms that cumulatively support the diagnosis of IBS: 1. Fewer than three bowel movements a week 2. More than three bowel movements a day 3. Hard or lumpy stools 4. Loose or watery stools 5. Straining during a bowel movement 6. Urgency 7. Feeling of incomplete emptying 8. Passing mucus during a bowel movement 9. Abdominal fullness, bloating or swelling Thompson WG Gut 1999;45(SuppIII):II43

31 Symptoms in IBS Major gastrointestinal symptoms (Rome-Manning criteria) Additional gastrointestinal symptoms Diverse symptoms of upper GI functional diseases and other GI signs (e.g. disturbing sound of bowel movement, anorectal discomfort) Extraintestinal functional symptoms Psychological alterations Interpretation of the symptoms is TYPICAL detailed; insufferable, intolerable

32 IBS: Alarm symptoms ( Red flags ) Rectal bleeding Weight loss Persistent diarrhea, steathorrea Constant and recent abdominal distension Anaemia, abnormal ESR Fever Thyroid dysfunction New onset in patients >50 years Family history of bowel cancer, IBD Nocturnal symptoms Rapid progression of symptoms/ change of the usual symptom pattern Heaton & Thompson, 1999; Paterson et al, 1999, Cash et al. 2005

33 IBS: Further evaluation Sigmoidoscopycolonoscopy Examination of stool Blood studies Imaging studies Drossman et al, 1997; Drossman, 1999

34 IBS: Differential diagnosis Malabsorption Dietary factors Infection Inflammatory bowel disease Psychological disorders Miscellaneous, GI tumors Drossman, 1999

35 IBS is a stable diagnosis After 6-30 years of follow-up organic GI disease developed in 2-5% of IBS patients after negative baseline investigation No change in IBS diagnosis: 95-98% El-Serag et al. Aliment Pharmacol Ther 2004;19:861. Owens et al. Ann Intern Med. 1995;122:107 22

36 IBS: sub-classification IBS is sub-classified into three types based on the primary bowel symptom constipation: IBS-C diarrhea: IBS-D alternation between constipation and diarrhea: IBS-A Patients may present with one or more mild-severe primary symptoms

37 Sub-classification of IBS: can vary with time 156 IBS patients from a population survey 0 months (%) Time 6 months (%) 12 months (%) IBS-C IBS-D IBS-A BUT: 36% at 6 months and 37% at 12 months had changed sub-group Koloski et al. Gastroenterology 2002;122(Suppl. 1):A507

38 Characteristics of IBS patients several medical reports more operations in the medical history know exactly how the medical system is working: utilization of health care resources doctor shopping refuse functional diagnosis => organic alterations frustration for both parties, (patient and doctor) establishment of a strong patient-physician relationship is key use of alternative medicine

39 Treatment / patient management

40 Treatment of IBS not a single study offers convincing evidence that any therapy is effective in treating the IBS symptom complex Placebo effect in IBS Klein KB. Gastroenterology 1988;95: Spiller RC. Am J Med 1999;107: 91S 97S.

41 Management of IBS Detailed patient history, physical examination => presumptive diagnosis Limited examinations Laboratory examinations Abdominal UH Fecal blood testing, microbiology Sigmoidoscopy (>50 years colonoscopy?) Symptom directed treatment Patient education Diet, life style Medication (symptomatic treatment) Special examinations in intractable cases

42 IBS: Management philosophy Identify concerns of the patient Explain the nature of the condition Reassure: IBS is a recognised clinical entity Involve patient: symptoms can fluctuate; diet or stress may precipitate symptoms Provide continuity: ongoing review may be important to the patient Set realistic expectations Drossman et al, 1997

43 Treatment paradigm in IBS From symptoms to hypothesis Pimentel Curr Treat Options in GE 2007

44 Medical therapy of IBS Anti-spasmodic, smooth muscle relaxants: mebeverine, pinaverium bromide, cimetropium, trimebutine Constipation: Fibre, osmotic laxatives (magnesium salt, lactulose) Anti-diarrheal agents: loperamide, diphenoxylate Antidepressants tricyclic antidepressants (desipramine, amitriptyline) and SSRI s (e.g. paroxetine) Camilleri M. Gastroenterology 2001;120: Jackson JL. Am J Med 2000;108:65-72.

45 Johanson JF Neurogastroenterol Motil 2004;16:

46 Efficacy of conventional drug therapies in IBS Mertz HR NEJM 2003

47 Psychoterapy Psychological therapy cognitive behavior, relaxation, psychotherapy, hypnotherapy, (50% reduction of symptoms): OR= 12, NNT 2!! For patients with severe IBS, both psychotherapy and paroxetine improve health-related quality of life at no additional cost psychotherapy, $976 [SD, $984], paroxetine, $1252 [SD, $1616]; and treatment as usual, $1663 [SD, $3177] Lackner JM J Consult Clin Psychol. 2004;72: CreedF Gastroenterology 2003;124:

48 Novel therapeutic possibilities Diarrhea 5-HT3 antagonists (e.g., alosetron, cilansetron): retard small bowel and colonic transit alosetron, number needed to treat (NNT) of 7 Constipation (1/4), ischaemic colitis (2/1000/3 months, 3/1000/6months) Anticholinergics, selective M3 type: antispasmodic with antidiarrheal potential CCK antagonist: dexloxiglumide IBS-C: Phase III trials were negative Constipation 5-HT4 partial agonists (e.g., tegaserod and prucalopride): accelerate small bowel and colonic transit, tegaserod 12 mg (RR 1.19), tegaserod 4 mg (RR 1.15), NNT of 14 and 20 Patel S Expert Opin Pharmacother. 2004;5: Evans BW Cochrane Database Syst Rev. 2004;(1):CD

49 Pain a2-adrenergic agonist (e.g., clonidine) reduces tone, increases compliance, decreases pain sensation during distention in health k-opioid agonist (e.g., fedotozine, asimadoline) increases threshold for distention-induced pain in IBS (partly through blockade of sodium channels) 5-HT 5-HT1A agonist? (buspirone): relaxes colonic tone, reduces sensation 5-HT3 antagonist: reduces colonic tonic response to feeding, colonic compliance, and sensation of volume distentions 5-HT4 antagonist: inhibits colonic sensation in experimental models 5HT4 agonist/5ht3 antagonist (renzapride): favorable in IBS-C Neurokinin antagonists (NK1-2-3): reduce visceral sensation; motor actions in colon depend on receptor subtype in experimental model

50 Rifaximin and SIBO: Percentage of Patients with Adequate Relief of Global IBS Symptoms in the TARGET 1 and TARGET 2 Studies Combined Pimentel M et al. N Engl J Med 2011;364:22-32

51 Treatment possibilities in IBS Mertz HR NEJM 2003;349:

52 Summary Symptoms usually develop in early adulthood Duration is long (decades) Diagnosis is stable Impairs QoL High health care costs Prognosis Quo ad vitam good, quo ad sanationem bad Functional disease does not protect against organic diseases (alarm symptoms)

53 Alosteron Camilleri M, Lancet 2000;355:

54 Alosteron-Male patients Equally effective in IBS-D in male patients 53% vs placebo 40% Phase II trial Chang L. Am J Gastroenterol 2005;100:

55 Alosteron-Long term use Long term efficacy (48week): Pain, discomfort: 52.1% vs. 43.9%, NNT: 12 Urgency control: 63.8% vs 52%, NNT 8 Chang WD. Am J Gastroenterol 2004;99:

56 Alosteron-Long term use Long term safety Constipation: 23% vs 5%, NNH 7 (first month) NNH 35 (subsequent months) Chang WD. Am J Gastroenterol 2004;99:

57 Cremonini F Neurogastroenterol Motil 2003;15:79-86.

58 Tegaserod: pivotal clinical studies Tegaserod 6 mg b.i.d. B301 1, B351 2, B358 3 Baseline 4 weeks Daily Tegaserod 2 mg b.i.d. Placebo 12 weeks Diary (paper or IVRS) Daily/weekly B301 1, B351 2 B301 1, B351 2, B358 3 Inclusion: Efficacy variables: Secondary: IBS-C, female Subject s Global Assessment (SGA) of relief of IBS symptoms SGA of relief of abdominal pain/discomfort Bowel movements, stool consistency, severity of bloating 1 Müller-Lissner et al. Aliment Pharmacol Ther 2001;15: Schmitt et al. Gut 1999;45(Suppl.V):A260 3 Novick et al. Aliment Pharmacol Ther 2002;16:

59 Müller-Lissner. Aliment Pharmacol Ther 2001;15:

60 Tegaserod Camilleri M. Gastroenterology 2001;120:

61 Tegaserod: relapse/retreatment 84% relapse / 8 weeks Müller-Lissner. Aliment Pharmacol Ther 2005;21:11-20

63 Hippocrates ( BC) Practice two things in your dealings with disease: either help or do not harm the patient.

IBS - Definition. Chronic functional disorder of GI generally characterized by:

IBS - Definition. Chronic functional disorder of GI generally characterized by: IBS - Definition Chronic functional disorder of GI generally characterized by: 3500 3000 No. of Publications 2500 2000 1500 1000 Irritable Bowel syndrome Irritable Bowel Syndrome 500 0 1968-1977 1978-1987