Epidemiology and Impact of IBS

Epidemiology and Impact of IBS Speaker: Nicholas Talley Mayo Clinic Jacksonville, FL

Epidemiology and Impact of IBS What is the worldwide prevalence of IBS? What is the natural history of IBS? What is the impact on healthcare utilization, cost and work productivity? What is the impact on quality of life? Do IBS patients undergo unnecessary surgery?

History of diagnostic approaches 1950s Increased gut motility not diagnostic 1970s Gut hypersensitivity not diagnostic 1980 to 2006 Symptom-based criteria Manning criteria Rome criteria

Irritable bowel syndrome (IBS) IBS is a chronic, episodic disease characterized by abdominal pain or discomfort associated with altered bowel function and often bloating Abdominal pain/discomfort associated with two of three features: <3 bowel movements (BM) per week or >3 BMs per day hard or lumpy stools, or loose or watery stools improved with defecation ACG IBS Task Force, Am J Gastro 2009; 104 (S1): S1-S35

What is Pain and Discomfort? Overall 3-month period prevalence 36%! Aching 13% Gripes 11%* Pain 10%* Tenderness 10% Sinking feeling 10% Burning sensation 10% Twinge 5%* Butterflies 5% Cramp 5% Colic 3%* Stitch 3% *Significantly more common in IBS Agréus L, Talley N et al., Scand J Gastro 2000; 35:142-51

Trust the British: Bristol Stool Form Scale Long transit (e.g. 100 hours) Type 1 Type 2 Separate hard lumps, like nuts, hard to pass Sausage-shaped but lumpy Type 3 Like sausage but with cracks on its surface Type 4 Like sausage or snake, smooth and soft Type 5 Soft blobs with clear-cut edges (passed easily) Short transit (e.g. 10 hours) Type 6 Type 7 Fluffy pieces with ragged edges. A mushy stool Watery no solid pieces Entirely liquid

Epidemiology IBS, constipation, diarrhea, dyspepsia and heartburn (GERD): All are common 62% report symptoms If you are symptom free, you are in the minority! Thompson WG et al. Dig Dis Sci 2002; 47: 225

Rome Versus Manning for the Diagnosis of IBS 15 95% CI 13 11 IBS (%) 9 7 5 3 1 Rome I Rome II Manning Boyce et al., Am J Gastro 2001; 95: 3176-83

World prevalence of IBS Canada 12% USA 10 20 20% Sweden 13% Belgium 8% Denmark 7% UK 22% The Netherlands 9% France 20% Germany 12% China 23% Spain 13% Japan 25% Nigeria 30% Australia 12% New Zealand 17% Camilleri M et al. Aliment Pharmacol Ther 1997;11:3 15; Drossman D. Dig Dis Sci 1993;38:1569 80 Talley N et al. Gastroenterology 1991;101:927 34; Müller-Lissner S et al. Digestion 2001;64:200 4 Talley N. Balliêre s Best Pract Res Clin Gastroenterol 1999;13:371 84 Thompson W et al. Dig Dis Sci 2002;47:225 35

Prevalence of IBS Saito Rome I Rome II Mearin Brommelaer West Thompson Boyce Gwee East 0 2 4 6 8 10 12 14 %

Prevalence of IBS: Olmsted County, MN, USA 20 18 Effect of definition Rate per 100 15 10 13.8 11.9 7.7 7.9 5 0 'Manning 2' 'Manning 3' 'Rome I' 'Manning 4' 'Rome I (modified)' Saito Y et al. Neurogastro Motil 2004;15:687-94

Age-specific prevalence 30 Proportion with IBS by age group, Olmsted County, MN 1992 Patients (%) 25 20 15 10 5 0 30 39 40 49 50 59 60 69 Years Rome 3 Rome 2 Manning 3 Manning 2 Saito Y et al. Am J Gastroenterol 2000;95:2816 24

IBS Prevalence by Age 30 % Rome II IBS 20 10 USA W. Europe Japan 0 China 0 10 20 30 40 50 60 70 80 Age (years) Hungin APS et al. APT 2005; 21:1365 Hungin APS et al. APT 2003; 17:643 Kumano H et al. AJG 2004; 99:370 Lau EMC et al. Dig Dis Sci 2002; 47: 621-24

Overall prevalence of IBS is greater in females 14 12 13.5 13.0 Female Male Prevalence (%) 10 8 6 4 9.4 2 0 15 34 35 44 >45 Age (years) Drossman D et al. Dig Dis Sci. 1993;38:1569 80

Gender distribution 80 75 Case definition 63 69 Female Male 60 Patients (%) 40 25 37 31 20 0 Self-report Rome Manning Hahn B et al. Dig Dis Sci 1997;42:2585 90

IBS Prevalence According to Sex 16 OR = 0.55 (0.5-0.61) OR = 0.52 (0.35-0.76) OR= 0.67 (0.45-0.99) OR = 0.99 (0.72-1.36) OR = 0.62 (0.3-1.26) % with Rome II IBS 12 8 Men Women 4 0 Andrews 2005 Thompson 2002 Sperber 2005 Gwee 2004 Talley 2001

Problems of Classifying IBS Perception of what constitutes IBS Uncertainties about disease mechanisms No coherent hypothesis! Not recommended by Rome II Committee BUT Some support from clinical / pathophysiologic studies and trials of serotonin agents (e.g. alosetron / tegaserod) Talley NJ & Spiller R, Lancet 2002; 360(9332):555-64

Prevalence by IBS subgroups Overall Survey respondents (%) 5.2 6.7 3.5 5.5 5.3 5.6 5.2 5.6 4.7 Females Males 3,022 residents surveyed in Minnesota 536 respondents IBS- IBS- IBSconstipation diarrhea mixed Talley N et al. Am J Epidemiol 1995;142:76 83

Prevalence by IBS Severity IBS Impact Scale (IBS-IS) Dimensions and symptom severity 7.0 6.0 5.0 4.0 3.0 Mild Moderate Severe Very severe 2.0 0 Daily activities Emotional stress Eating habits Sleep disturbance Fatigue Talley et al. Am J Epidemiol.1995; 142:76

IBS Prevalence According to Socioeconomic Status % Rome II IBS 25 20 15 10 5 0 Very low Low High Very high Socioeconomic status Minocha 2006 (US) Wilson 2004 (UK) Andrews 2005 (US) Howell 2004 (New Zealand)

Incidence of IBS in the General Population 4 3 % Annual incidence 2 1 0 Marshall 06 Mearin 05 Rome I Parry 03

Familial Association in Adults with Dyspepsia and IBS 2.5 2.0 1.8 (1.1-3.0) 2.3 (1.3-3.9) Learned illness behavior? Genetic factors? Odds ratio 1.5 1.0 0.5 Psychosocial factors? Environmental factors? Dyspepsia IBS Locke et al. Mayo Clin Proc 2000; 75:907

Chronicity of symptoms Owens 95 Year 5 Harvey 87 Svendsen 85 Sullivan 83 Holmes 82 Hawkins 71 Symptoms retained 75% 0 50 100 (%) Owens et al. Ann Intern Med 1995;122:107

Natural History of IBS Episodes Cyclical (fluctuating) condition 12-week observational study 1 Pain/discomfort: 33% of days Bloating: 28% of days Altered stool form: 25% of days Approximately 50% of patients were symptom free for half the time 8-week observational study 2 Flares of severe symptoms over 5-8 day intervals 1 Hahn B et al. Dig Dis Sci 1998;43 (12):2715-18. 2 Stevens JA et al. Behav Res Ther 1997;35(4):319-26.

Natural history of IBS: Disappearance in the general population % 90 80 70 60 50 40 30 20 10 0 Dyspepsia Irritable bowel syndrome 30-39 40-49 50-59 60-69 Age group Talley N et al. Am J Epidemiol 1992; 136:165-77

Symptom Turnover 17% 18% Initial survey 12 20 months later n=835 n=690 Talley N et al. Am J Epidemiol 1992;136:165 77

Distribution of Symptom Profile in Dyspeptic Subjects After 1 and 7 Years IBS Dyspepsia Symptomfree Minor symptoms 1989 1988 Dyspepsia Reflux n=99 IBS Dyspepsia Symptomfree Minor symptoms 1995 Agreus et al. Am J Gastroenterol 2001; 96:2905 Reflux

Turnover of IBS Dyspepsia Rome I 1989 n=211 IBS Other minor FBD Minor IBS Other FBD Rome II 1999 Subjects meeting original Rome but not Rome II criteria (n=146) Diagnoses: 40%"minor" IBS (IBS symptoms of less than 12 wk duration), 37% functional constipation, 12% alternating bowel habit, 7% functional diarrhea, 3% functional abdominal bloating, and 1% unspecified Mearin et al. Am J Gastroenterol. 2004; 99:122

Risk factors for IBS Population based survey: n=643 (72%) - 12% IBS Significant associations: Analgesics (acetaminophen, aspirin, NSAIDs) for reasons other than IBS Self reported food allergy or sensitivity Somatic symptoms No associations for age, gender, body mass index, smoking history, alcohol use, educational level, exposure to pets in the household, or water supply. Locke et al. Am J Gastroenterol 2000;95:157-65

Risk factors for IBS Among Women 50-69 Risk Factor Women, aged 50-69, using HRT Relative 2.2 Current HRT use 1.5 Past HRT use 2 Pain-related disorders 1.6 Gastroenteritis 4.1 Psychological / neurological 1.4 >6 GP visits / year 2.3 Ruigomez A et al. Maturitas 2003; 44; 133-40

Risk factors for IBS Antibiotic use and childhood affluence 421 subjects attending a GP screening clinic: 11% IBS Antibiotic use 1.8 3.7 * 7.6 Childhood density < 1/ room 1.6 3.5 * 7.6 0 Odds ratios Mendal & Kumar Eur J Gastroenterol Hepatol 1998

IBS Following Gastroenteritis Systematic review 8 studies 588,061 subjects 3-12 months follow-up 9.8% IBS in cases Ji 05 2.8 (1.0, 7.5) Mearin 05 8.7 (3.3, 22.6) Wang 04 10.7 (2.5, 45.6) Okhuysen 04 10.1 (0.6, 181.4) Cumberland 03 6.6 (2.0, 22.3) Ilnyckyj 03 2.7 (0.2, 30.2) Parry 03 9.9 (3.2, 30.0) Rodriguez 99 11.3 (6.3, 20.1) 1.2% IBS in Pooled estimate 7.3 (4.8, 11.1) controls 0.2 0.5 1 2 5 10 100 1000 Odds ratio (95% confidence interval) Halvorson HA et al. AJG 2006; 101: 1894

Risk Factors for IBS After Acute Gastroenteritis 8 6 4 Odds ratio 2 0-2 -4-6 -8 Female gender Age Diarrhea Abdominal cramps Weight loss Marshall JK et al. Gastroenterology 2006; 131:445

Impact of IBS on QoL compared with the general population 100 IBS (n=877) US general population (n=2,474) 80 SF-36 score 60 40 20 0 Physical function Role limitations physical Bodily pain Emotional well-being Role limitations emotional Energy/ fatigue Social functioning General health All comparisons p<0.001 Gralnek IM et al. Gastroenterology 2000;119:654 60

Clinical predictors of physical HRQOL in IBS 0 Something Flares >5 MD Tire Low in Severe Painful serious >24 visits easily energy symptoms symptoms wrong hours Change in SF-36 (%) 2 4 6 8 7.1 6.5 4.9 4.4 3.7 10 9.2 9 Spiegel et al. Arch Intern Med 2004 R 2 = 0.39; p<0.001 Intercept = 55.9 770 Rome + patients 2/3 clinic pts, 1/3 self-referred BSQ, SCL-90, SF-36

Clinical predictors of physical HRQOL in IBS 0 Low Interference Feel Feel Feel Sleep Tire sexual with sexual tense nervous hopeless difficulties easily interest Fcn Change in SF-36 (%) 3 6 9 12 8.6 8.5 5.5 4.5 4.1 3.7 15 13.6 Spiegel et al. Arch Intern Med 2004 R 2 = 0.39; p<0.001 Intercept = 55.9 770 Rome + patients 2/3 clinic pts, 1/3 self-referred BSQ, SCL-90, SF-36

Is lower quality of life a consequence of IBS or a cause? Individuals, 50 59 yr. contacted via postal questionnaire Manning criteria for IBS diagnosis Of 8,407 individuals originally involved, 3,873 (46%) provided symptom data at baseline and 10-yr follow-up 542 (15%) developed new-onset IBS at 10-yr follow-up After multivariate logistic regression, lower quality of life at baseline (odds ratio [OR] 4.41, 99% confidence interval [CI] 2.92 6.65), a significant independent risk factor for new-onset IBS Ford et al. Am J Gastroenterol. 2008;103:1229-39 8,407 originally enrolled 6,416 traced and sent questionnaire 4,003 returned the questionnaire 3,873 gave fully analyzable data at baseline and 10 years 3,659 asymptomatic or not meeting diagnostic criteria for IBS at baseline 1,991 deceased or no contact address 2,413 did not respond 130 incomplete data at baseline or 10 years 214 symptomatic at baseline 37

Direct Cost of IBS Patients Versus Controls in the US 5000 Mean cost $/patient/yr 4000 3000 2000 1000 * * * IBS Control * p<0.05 * 0 Leong 1998 Levy 1995 Longstreth 2000 Patel 1998 Talley 1992 Maxion-Bergemann S et al. Pharmacoeconomics 2006; 24:21

Health-care Costs of IBS Patients Total healthcare costs over 1-year ($) + 5000 4000 3000 2000 2,625 3,324 3,783 * 4,015* non-ibs, n=1854 IBS (mild), n=165 IBS (moderate), n=225 IBS (severe), n=138 1000 0 *p<0.05 vs non-ibs + total costs include outpatients, inpatients, pharmacy-, radiology- and laboratory-costs IBS patients with moderate or severe abdominal pain / discomfort had higher healthcare costs vs. non-ibs patients Longstreth et al, Am J Gastroenterol 2003; 98: 600

US Annual Costs (US$ Millions) Drugs Visits Ulcerative colitis 38 138 Foodborne Illness 155 38 IBS 228 80 Sandler, et al. Gastroenterol 2002; 122:1500

Cost of IBS Systematic review 18 studies from UK and US Direct costs $348-8750 per patient Indirect costs $355-3344 per patient Lost work days per year 8.5-21.6 Maxion-Bergemann S et al. Pharmacoeconomics 2006; 24: 21-37

Impact of IBS on productivity Cut back on workdays Missed workdays Worked fewer hours 15 30 46 Changed to working at home Lost a job or quit work 12 12 Changed jobs for health reasons Schedule 8 9 0 10 20 30 40 50 n=287 respondants Hahn et al. Digestion 1999;60:77 81

Who treats IBS? IBS is a common diagnosis in primary care and gastroenterology practices 12% IBS 28% IBS All other diagnoses 88% All other diagnoses 72% Primary care Gastroenterology Mitchell C et al. Gastroenterology 1987;92:1282 4 Drossman D. Gastroenterology 1997;112:2120 37

Healthcare seeking Non-IBS 85% IBS 15% No physician visits Physician visits Predictors of healthcare seeking?

Physician visits per year 6 US householder survey GI Non-GI Physician visits per year 4 2 0 IBS Normal * P < 0.05 Drossman D et al. Dig Dis Sci. 1993;38:1569 80

Health-care Usage by IBS Patients 50 Number of prescriptions over 2 years 40 40.4 *** 30 27.7 20 10 ***p<0.001 0 IBS Non-IBS IBS patients had significantly more prescriptions than non- IBS patients Longstreth et al, Am J Gastroenterol 2003; 98: 600

Factors Affecting Specialist Referral Health care system Diagnostic certainty Specialist availability Primary physician time constraints Special test need Symptom response Patient attitude

Excess and Unnecessary Abdominal and Pelvic Surgery in IBS IBS patients have, compared to controls: more cholecystectomies [4.6% vs. 2.4% (odds ratio: 1.9; p<0.01)] more hysterectomies [18% vs. 12% (odds ratio: 1.6; p<0.01)] IBS patients with pelvic pain have more hysterectomies: than those without pelvic pain [71% vs. 41% (odds ratio: 3.6; p<0.05)] than patients with IBD [71% vs. 14% (odds ratio: 15.6; p<0.05)] An excess of 16 cholecystectomies and 57 hysterectomies performed per 1000 women with IBS Hasler & Schoenfeld Aliment Pharmacol Ther 2003; 17: 997

Epidemiology of IBS General population studies show IBS as defined by Rome is common 10% around the world suffer with IBS and it is chronic Abdominal pain, bloating and constipation and/or diarrhea Some lose and other gain the symptoms; IBS may transform into other GI syndromes The condition impairs quality of life and is very costly Unnecessary surgical rates are increased in IBS