Under Pressure: The Need to Expedite IBS Diagnosis and Treatment in

Primary Care

June 23, 2012

New York, New York

Educational Partner: CME Incite, LLC

Session 4

Session 4: Under Pressure: The Need to Expedite IBS Diagnosis and Treatment in Primary Care Learning Objectives

1. Diagnose IBS based on symptoms that may be shared with other functional gastrointestinal disorders or organic diseases.

2. Compare and contrast the efficacy and safety of available pharmacologic and nonpharmacologic treatment options for IBS.

3. Apply appropriate and comprehensive treatment strategies to enhance the care of patients with IBS. Faculty Lawrence R. Schiller, MD Program Director Gastroenterology Fellowship Baylor University Medical Center Dallas, Texas Dr Lawrence Schiller was born in Philadelphia and attended Pennsylvania State University and Jefferson Medical College of Philadelphia. He completed his internal medicine training at Temple University Hospital, also in Philadelphia, and then served in the US Army Medical Corps for two years. Dr Schiller moved to Dallas in 1978 for gastroenterology training at the University of Texas (UT) Southwestern Medical Center, where he remained on the faculty at the medical school; he was also an attending physician at the Dallas VA Hospital for five years. In 1985, Dr Schiller moved to Baylor University Medical Center to continue research with Dr John Fordtran, and has been there ever since, most recently serving as program director for the gastroenterology fellowship. Dr Schiller has been involved in patient care as a founding partner of Digestive Health Associates of Texas, one of the largest single-specialty gastroenterology practices in America, and has continued with research and education activities at Baylor and UT Southwestern. He is currently attending physician and chairman of the Institutional Review Board for Human Subject Protection at Baylor as well as clinical professor of internal medicine at UT Southwestern, where he has won two fellow teaching awards. Dr Schiller has been elected to fellowships in the American College of Physicians and the American College of Gastroenterology (ACG) and has served as ACG governor of the North Texas region. Dr Schiller is currently ACG president-elect. He also has served as president of the Texas Society for Gastroenterology and Endoscopy. Dr Schiller has published more than 80 papers and 45 book chapters dealing with gastric physiology, intestinal transport, diarrheal diseases, and motility disorders. Brooks D. Cash, MD, FACP, FACG, AGAF Professor of Medicine Uniformed Services University of the Health Sciences Deputy Commander of Medicine Walter Reed National Military Medical Center Bethesda, Maryland Brooks D. Cash, MD, FACP, FACG, AGAF, is professor of medicine at the Uniformed Services University of the Health Sciences, in Bethesda, Maryland, where he has held a faculty position since 1996. Dr Cash earned his undergraduate degree in business administration (finance) with honors from the University of Texas in Austin. He earned his medical degree from the Uniformed Services University of Health Sciences and completed his internship, residency, and gastroenterology fellowship at the National Naval Medical Center in Bethesda, Maryland. Dr Cash is a diplomate of the American Board of Gastroenterology. He is a fellow of the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, where he serves as chair of the Standards of Practice Committee. Dr Cash serves on the Rome Committee for Functional Gastrointestinal Disorders and has authored multiple articles and book chapters on a variety of gastrointestinal topics including irritable bowel syndrome and chronic constipation, colorectal cancer screening, CT colonography, acid peptic disorders, Barrett’s esophagus, and evidence-based medicine. He serves as associate editor for the American Journal of

Session 4

Gastroenterology and is an editorial board member and reviewer for multiple internal medicine and gastroenterological medical journals. Dr Cash also serves as governor of the Military Region of the American College of Gastroenterology. Faculty Financial Disclosure Statements The presenting faculty reports the following: Dr Schiller has no financial relationships to disclose. Dr Cash is a consultant for Ironwood Pharmaceuticals, Inc.; Salix Pharmaceuticals, Inc.; Takeda Pharmaceutical Company; and Forest Laboratories, Inc. He serves as a speaker for Salix Pharmaceuticals, Inc.. and Takeda Pharmaceutical Company. Education Partner Financial Disclosure Statement The content collaborators at CME Incite report the following: Rose O’Connor, PhD, has no financial relationships to disclose. Suggested Reading List Biesiekierski JR, Newnham ED, Irving PM, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol. 2011;106(3):518-514. Brandt LJ, Chey WD, Foxx-Orenstein AE, et al; American College of Gastroenterology Task Force on Irritable Bowel Syndrome. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2009;104(suppl 1):S1-S35. Cash BD, Chang E, Talley NJ, Wald A. Fresh perspectives in chronic constipation and other functional bowel disorders. Rev Gastroenterol Disord. 2007;7(3):116-133. Ford AC, Talley NJ. IBS in 2010: advances in pathophysiology, diagnosis and treatment. Nat Rev Gastroenterol Hepatol. 2011;8(2):76-78. Halpert A, Dalton CB, Palsson O, et al. What patients know about irritable bowel syndrome (IBS) and what they would like to know. National Survey on Patient Educational Needs in IBS and development and validation of the Patient Educational Needs Questionnaire (PEQ). Am J Gastroenterol. 2007;102(9):1972-1982. Hasler WL. Traditional thoughts on the pathophysiology of irritable bowel syndrome. Gastroenterol Clin North Am. 2011;40(1):21-43. Johannesson E, Simrén M, Strid H, Bajor A, Sadik R. Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2011;106(5):915-922. Johnston JM, Kurtz CB, Macdougall JE, et al. Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation. Gastroenterology. 2010;139(6):1877-1886. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5):1480-1491. Pimentel M, Lembo A, Chey WD, et al; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22-32.

1

Lawrence R. Schiller, MD, FACGDigestive Health Associates of Texas

Baylor University Medical CenterDallas, Texas

Brooks D. Cash, MD, AGAF, FASGE, FACG Professor of Medicine

Uniformed Services University of the Health SciencesDeputy Commander for Medicine

Walter Reed National Military Medical CenterBethesda, Maryland

New York, New YorkJune 23, 2012

Diagnose IBS based on symptoms that may be shared with other functional GI disorders or organic diseases

Compare and contrast the efficacy and safety of available pharmacologic and nonpharmacologic treatment options for IBS

Apply appropriate and comprehensive treatment strategies to enhance the management of patients with IBS

IBS, irritable bowel syndrome; GI, gastrointestinal.

A3309 Alosetron Amitriptyline Atropine Cholestyramine Citalopram Desipramine Diphenoxylate Doxepin Fluoxetine Hyoscyamine Imipramine Linaclotide Loperamide Lubiprostone Paroxetine Prucalopride Psyllium Rifaximin

No trade name Lotronex Elavil, Tryptizol, Laroxyl, etc Sal-tropine Questran Celexa Norpramin, Pertofane Lomotil, Lonox, Dimotal, etc Adapin, Silenor, Sinequan, etc Prozac, Sarafem, Fontex, etc A-Spas, Anapaz, Cytospaz, etc Antideprin, Deprimin, Deprinol, etc No trade name Imodium, Diar-Aid, Diamode, etc Amitiza Paxil, Aropax, Seroxat, Pexeva, etc Resolor Fiberall, Benefiber, Metamucil, etc Xifaxan

A 43-year-old patient presents with IBS symptoms for >3 months prior to initial visit without the presence of alarm features. What should be your next course of action?

1. Watch and wait for emergence of alarm features2. Perform routine lab tests (CBC, CMP, TSH, stool

O+P, abdominal imaging) 3. Refer for colonoscopy4. Begin treatment for IBS immediately5. Unsure

CBC, complete blood count; CMP, comprehensive metabolic panel; TSH, thyroid-stimulating hormone, O+P, ova and parasites.

How would you distinguish IBS from other functional GI disorders, such as functional constipation (FC) or functional diarrhea (FD)?

1. Pain is more prominent than bowel disturbance in functional constipation or functional diarrhea

2. Pain is more prominent than bowel disturbance in IBS3. Frequency of bowel habits differs between FC/FD

and IBS4. Changes in diet have more impact on patients with

IBS than on patients with FC or FD5. Unsure

Which of the following therapies is an evidence based treatment option for patients with IBS-C?

1. Hyoscyamine

2. Lubiprostone

3. Loperamide

4. Alosetron

5. Unsure

IBS-C, IBS Constipation.

2

What medication would you recommend for a 57-year-old woman with severe IBS-D who has previously tried anticholinergics, loperamide, SSRIs and dietary changes, but still has abdominal pain and urgency?

1. Diphenoxylate with atropine 2. Lubiprostone 3. Polyethylene glycol 4. Alosetron 5. Any of the above 6. Unsure

IBS-D, IBS Diarrhea; SSRIs, selective serotonin reuptake inhibitors; PEG, polyethylene glycol.

AC, a 45-year-old woman, presents with a 6-year history of abdominal pain and variable bowel habits Crampy pain is located in left lower quadrant

Pain peaks just before bowel movement

Pain is relieved by defecation

Bowel movements vary in consistency from loose to hard

Frequency of bowel movements varies from once weekly to 4 times per day

Other symptoms include indigestion, early satiety, bloating, excessive flatulence, and belching

Patient has experienced no weight loss or rectal bleeding

Previous evaluation included colonoscopy with biopsies (negative), endoscopy with biopsies (negative), and abdominal sonogram (negative)

Patient has tried lactose-free diet, increased dietary fiber, dicyclomine, and hyoscyamine, all without benefit

Physical examination is unremarkable

1. Past surgical history

2. History of migraine headaches

3. Discussion of life stressors and relation to symptoms

4. Discussion of physical and sexual abuse

5. Family history of digestive symptoms

ARS, audience response system.

?

1. Laboratory tests: CBC, CMP, TSH

2. Pelvic examination

3. Diet and symptom diary for 2 weeks

4. CT scan of abdomen/pelvis

5. Repeat colonoscopy and endoscopy

CT, computed tomography.

?

3

Lawrence R. Schiller, MD, FACG

Worldwide prevalence: 7% to 10%

1.5 times more prevalent in women

More commonly diagnosed in patients <50 years of age

More common in lower socioeconomic groups

Patients with IBS have more physician visits, more hospitalizations, more missed workdays, more prescriptions, and more diagnostic tests than those without the disorder

American College of Gastroenterology Task Force on Irritable Bowel Syndrome; Brandt LJ, et al. Am J Gastroenterol. 2009;104(suppl 1):S1-S35.

IBS is a syndrome—a collection of symptoms

Diagnosis is possible by taking a thorough history of symptoms

Since symptoms may be due to other disorders, the provider must consider alternative organic diagnoses

Serious organic illnesses typically produce alarm symptoms

Abdominal painAnywhere in abdomen

Characteristically relieved by defecation

Altered stool frequencyExcess frequency: >2 bowel movements/day

Infrequency: <3 bowel movements/week

Altered stool formLoose to lumpy

Longstreth GF, et al. Gastroenterology. 2006;130(5):1480-1491; erratum in: Gastroenterology. 2006;131(2):688.

IBS-C IBS-M

IBS-U IBS-D

100

75

50

25

00 25 50 75 100

Har

d o

r L

um

py

Sto

ols

(%

)

Loose or Watery Stools (%)

IBS-C: Constipation-predominant IBS

IBS-D: Diarrhea-predominant IBS

IBS-M: Mixed IBS (hard and loose stools over periods of weeks and months)

IBS-U: Unsubtyped IBS

Longstreth GF, et al. Gastroenterology. 2006;130(5):1480-1491; erratum in: Gastroenterology. 2006;131(2):688.

Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis

Onset associated with a change in frequency

of stool

Onset associated with a change in

form of stool

Recurrent abdominal pain or discomfortat least 3 days/month in the last 3 months

associated with ≥2 of the following:

Improvement with defecation

Additional IBS “testing,” including routine laboratory tests and colonoscopy, unnecessary unless alarm features present

4

Refractory or worsening abdominalsymptoms

Older patient (≥50 years of age;≥45 years of age if black)

Blood in stools Anemia Weight loss (unintentional) Anorexia Family history of organic

GI disease

Lembo A, Camilleri M. N Engl J Med. 2003;349(14):1360-1368; Brandt LJ, et al. Am J Gastroenterol. 2005;100(suppl 1):S5-S21; Cash BD, et al. Rev Gastroenterol Disord. 2007;7(3):116-133.

Further investigation warranted

Consider colonoscopy

Routine laboratory tests (CBC, CMP) and TSH, stool O&P, abdominal imaging not recommended

Serologic testing for celiac disease (IBS-D/M) recommended

Lactose breath testing selected cases

Colonoscopy recommended if >50 years of age, with biopsies in refractory IBS-D (to exclude microscopic colitis)

American College of Gastroenterology Task Force on Irritable Bowel Syndrome; Brandt LJ, et al. Am J Gastroenterol. 2009;104(suppl 1):S1-S35.

ACG, American College of Gastroenterology.

Dysmotility

Hypersensitivity

Disordered brain processing

Enteric nervous system dysfunction SERT activity

Postinfectious IBS

Somatization syndrome

Small intestinal bacterial overgrowth

Mast cell dysfunction

Dysbiosis

Food intolerances

Food allergy

Genetics

Hasler WL. Gastroenterol Clin North Am. 2011;40(1):21-43; Ford AC, Talley NJ. Nat Rev Gastroenterol Hepatol. 2011;8(2):76- 78.

SERT, serotonin transporter.

Other functional GI disordersFunctional constipation, functional diarrheaPain less prominent than bowel disturbance

Functional abdominal painBowel disturbance less prominent

Gastrointestinal Colorectal cancer Diverticular disease

GynecologicOvarian cancer Endometriosis

DrugsOpiates Anticholinergics Antidepressants

Metabolic/endocrine Hypothyroidism Diabetes

Neurologic Parkinson’s diseaseMultiple sclerosis Autonomic

neuropathy

Other Amyloidosis Scleroderma

Candelli M, et al. Hepatogastroenterology. 2001;48(40):1050-1057; Locke GR III, et al. Gastroenterology. 2000;119(6):1766-1778.

5

Dietary factors LactoseGlutenOther FODMAPS

Drugs InfectionGiardiasis Amebiasis

Malabsorption Celiac disease

Inflammatory bowel disease Crohn’s disease Ulcerative colitisMicroscopic colitis

Psychological Panic disorder Somatization Depression

FODMAPs, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols.

Candelli M, et al. Hepatogastroenterology. 2001;48(40):1050-1057; Locke GR III, et al. Gastroenterology. 2000;119(6):1766-1778. Longstreth GF, et al. Gastroenterology. 2006;130(5):1480-1491; erratum in: Gastroenterology. 2006;131(2):688;American College of Gastroenterology Task Force on Irritable Bowel Syndrome; Brandt LJ, et al. Am J Gastroenterol. 2009;104(suppl 1):S1-S35.

Identify IBS symptoms, presence of alarm features

Meets criteria, no alarm features make diagnosis of IBS

Doesn’t meet criteria, has alarm features look for alternative diagnosis

Symptomatic treatment for predominant symptoms

Assess response to treatment

Good response continue Rx Poor response reassess

A 43-year-old patient presents with IBS symptoms for >3 months prior to initial visit without the presence of alarm features. What should be your next course of action?

1. Watch and wait for emergence of alarm features2. Perform routine lab tests (CBC, CMP, TSH, stool

O&P, abdominal imaging) 3. Refer for colonoscopy4. Begin treatment for IBS immediately5. None of the above6. Unsure

How would you distinguish IBS from other functional GI disorders, such as functional constipation (FC) or functional diarrhea (FD)?

1. Pain is more prominent than bowel disturbance in functional constipation or functional diarrhea

2. Pain is more prominent than bowel disturbance in IBS

3. Frequency of bowel habits differs between FC/FD and IBS

4. Changes in diet have more impact on patients with IBS than on patients with FC or FD

5. Unsure

Brooks D. Cash, MD, AGAF, FASGE, FACG

Diet, lifestyle advice

Positive diagnosis

Explain, reassure

Drossman DA, et al. Am J Gastroenterol. 2011;106:1749-1759.

Follow-up visit

Manage stress

Drug therapy

+

Psychological treatments

Goal: improved function

Continuing care +

Mild

(40%)

Moderate

(35%)

Severe

(25%)

6

Lifestyle1

Survey of 1242 patients: following interventions improved symptoms Small meals (69%), avoiding fat (64%), increasing fiber

(58%), avoiding milk products (54%)

Food allergy2—limited evidence

Lactose3—higher % of lactose maldigestion

Gluten4,5—studies indicate possible link

Fructose intolerance6—studies indicate possible link

1. Halpert A, et al. Am J Gastroenterol. 2007;102:1972-1982. 2. Locke GR 3rd, et al. Am J Gastroenterol. 2200;95:157-165. 3. Brandt LJ, et al. Am J Gastroenterol. 2009;104(suppl 1):S1-S35. 4. Wahnschaffe U, et al. Clin Gastroenterol Hepatol. 2007;5: 844-850. 5. Biesiekierski JR, et al. Am J Gastroenterol. 2011;106:508-514. 6. Shepherd SJ, et al. J Am Diet Assoc. 2006;106:1631-1639.

Treatment

Modality

Studies, N

N RR

(95% CI)Pts CCognitive behavioral therapy (CBT)

7 279 212 0.60 (0.42-0.87)

Hypnotherapy 2 20 20 0.48 (0.26-0.87)

Multicomponent psychological therapy

4 106 105 0.69 (0.56-0.86)

Stress management 1 18 17 0.34 (0.16-0.73)

Dynamic psychotherapy 2 138 135 0.60 (0.39-0.93)

Ford AC, et al. Gut. 2009;58:367-378.

Brandt LJ, et al. Am J Gastroenterol. 2002;97(11 suppl):S7-S26. Drossman DA, et al. Gastroenterology. 2002;123:2108-2131.

Abdominal pain/discomfort

Antispasmodics*

Antidepressants*

TCAs/SSRIs

Alosetron (5HT-3 antagonist)

Abdominalpain/

discomfort

Bloating/distension

Altered bowelfunction

Constipation Fiber* MOM/PEG solution* Lubiprostone (chloride

channel activator)

Diarrhea Loperamide* Cholestyramine* Alosetron Rifaximin*

Bloating

Rifaximin* ? Probiotics

*These agents are not currently FDA-approved for IBS. TCAs, tricyclic antidepressants.

Randomized, placebo-controlled trial (N=275 patients with IBS)

Primary endpoint: adequate symptom relief ≥2 weeks in previous month, analyzed after 1, 2, and 3 months

RESULT Higher % responders in psyllium vs placebo group

during first month (57% vs 35%) Higher % responders through 2 months of

treatment (59% vs 41%)

Bijkerk CJ, et al. BMJ. 2009;339:3154-3160.

No adult studies of laxatives in IBS-C1

27 adolescents: PEG improved number of bowel movements (P<0.05) but not pain in IBS-C patients2

0

1

2

3

4

5

6

7

8

#BMs Pain Level

Pre-Treatment

Post-Treatment

1. Brandt L, et al. Am J Gastroenterol. 2009;104(suppl):S1-S35. 2. Khoshoo V, et al. Aliment Pharmacol Ther. 2006;23:191-196.

7

2 Phase III 12-week randomized controlled trials

Results: patients receiving lubiprostone (8 μg BID) twice as likely to achieve overall response

7.8% difference (P=0.001) vs placebo

0

5

10

15

20

Placebo n=388 Lubiprostonen=783

Res

po

nd

er (

%)

Drossman DA, et al. Aliment Pharmacol Ther. 2009;29:329-341.

Ensure absence of mechanical obstruction before beginning therapy

Low doses 2 mg once or twice daily may be effective to decrease stool frequency, improve stool consistency

No impact on symptoms of abdominal discomfort, bloating, or global IBS

2 randomized controlled trials in IBS (N=42) show efficacy for diarrhea

Adverse effects: dizziness, abdominal pain/bloat, constipation, dry mouth, fatigue

http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed May 15, 2012.

Study NFemale,

%Response:

Alosetron, %Response: Placebo, %

TherapeuticGain, %

Camilleri1 370 53 60 33 27

Camilleri2 647 100 41 29 12

Camilleri3 626 100 43 26 17

Lembo4 801 100 73 57 16

Jones5* 623 100 58 48 10

*Comparison mebeverine† i/o placebo.

1. Camilleri M, et al. Aliment Pharmacol Ther. 1999;13:1149-1159. 2. Camilleri M, et al. Lancet. 2000;355:1035-1040.3. Camilleri M, et al. Arch Intern Med. 2001;161:1733-1740. 4. Lembo T, et al. Am J Gastroenterol. 2001;96:2662-2670.5. Jones R, et al. Aliment Pharmacol Ther. 1999;13:1419-1427.

†Mebeverine not available in the US

Female patients with chronic, severe IBS-D who failed other treatments Dose: 0.5-1.0 mg QD to BID

Patient education regarding possible serious adverse effects of severe constipation or ischemic colitis 0.95 cases of ischemic colitis/1000 patient-years 0.36 cases of severe constipation/1000 patient-years

Ischemic colitis usually occurs within the first month of therapy if it occurs

Prescribing program mandated by FDA Requires patient to sign attestation form

http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed May 15, 2012. Whorwell PJ, et al. Am J Gastroenterol. 2006;101:1581-1590.

SGA: (Subjects’ Global Assessment) a yes/no response to the following question:

“Please consider how you felt in the past week in regard to your IBS, in particular your general well being, and symptoms of abdominal discomfort or pain, bloating or distension, and altered bowel habit. Compared with the way you felt before beginning the medication, have you had adequate relief of your IBS symptoms?”

8070

60

50

4030

PlaceboB Infantis1 x 106

B Infantis1 x 108

B Infantis1 x 1010

An

swer

ing

“Y

es”

at

Wee

k 4

(%)

P=0.0118

20

8

22 randomized controlled trials comparing 12 different antispasmodics vs placebo (N=1778 patients)

Significant heterogeneity among studies

Many agents not available in US

Appear most useful for abdominal pain

In meta-analysis, symptoms persist in 39% of patients receiving antispasmodics vs 56% of placebo-treated patients (RR: 0.68; 95% CI: 0.57-0.81)

Ford AC, et al. BMJ. 2008;337:a2313.

TCAs: 9 studies (N=319 drug vs 256 control) Imipramine, desipramine, amitriptyline, doxepin*;

doses 10-150 mg

Meta-analysis favors treatment

SSRIs: 5 studies (N=113 drug vs 117 control) Fluoxetine, paroxetine, citalopram*; dose 10-40 mg

Meta-analysis favors treatment

Ford AC, et al. Gut. 2009;58:367-378.

*These agents are not currently FDA-approved for IBS.

Phase III randomized controlled trial in IBS-C of 290 μg of once-daily linaclotide followed by a 4-week randomized withdrawal period

N=800 (n=405 receiving linaclotide, n=395 placebo)

RESULT Linaclotide-treated patients experienced significant

improvement in all 4 endpoints (P<0.05) compared to placebo treated patients

No evidence of rebound worsening with randomized withdrawal of linaclotide Diarrhea most common adverse event (19.5% vs 3.5%,

P<0.05)

Rao S, et al. Am J Gastroenterol. 2012; In press.

*Linaclotide not currently FDA-approved for IBS.

Rao S, et al. Am J Gastroenterol. 2012; In press.

*Linaclotide not currently FDA-approved for IBS. CBSM , complete spontaneous bowel movements. RW, randomized withdrawal.

9

Rao S, et al. Am J Gastroenterol. 2012; In press.

*Linaclotide not currently FDA-approved for IBS. RW, randomized withdrawal.

Me

an

% C

ha

ng

e f

rom

B

as

eli

ne

+/-

SE

M

2 Phase III randomized controlled trials; N=1260 patients

Rifaximin 550 mg tid x 2 weeks; patients followed additional 10 weeks

40.7% vs 31.7% with adequate relief of global symptoms (P<0.001)

0

5

10

15

20

25

30

35

40

45

T-I T-II Comb

Rifaximin

Placebo

T-I, TARGET 1 trial; T-II, TARGET 2 trial; Comb, Combination of both trials.*Rifaximin is not currently FDA-approved for IBS.

Pimentel M, et al. N Engl J Med. 2011;364:22-32.

Not systemically absorbed

Doses studied for IBS: 400 mg BID to 550 mg TID

Primary adverse effects include headache, abdominal pain, and upper respiratory tract infection

Ford AC, et al. Clin Gastroenterol Hepatol. 2009;7:1279-1286. Pimentel M, et al. N Engl J Med. 2011;364:22-32.

Treatment depends on severity of IBS symptoms

Management of diet, exercise, and sleep build foundation for success of other therapies Limited evidence but useful starting points

Pharmacologic therapies directed at predominant symptoms

Evidence-based treatments include IBS-C: lubiprostone, SSRIs

IBS-D: alosetron, TCAs Antibiotics and probiotics may help with bloating

Centrally acting therapies (eg, antidepressants) in select patients may help with improving general well being

Novel agents in development Linaclotide and rifaximin are promising therapies for IBS

Which of the following therapies is an evidence based treatment option for patients with IBS-C?

1. Hyoscyamine

2. Lubiprostone

3. Loperamide

4. Alosetron

5. Unsure

What medication would you recommend for a 57-year-old woman with severe IBS-D who has previously tried anticholinergics, loperamide, SSRIs and dietary changes, but still has abdominal pain and urgency?

1. Diphenoxylate with atropine 2. Lubiprostone 3. Polyethylene glycol 4. Alosetron 5. Any of the above 6. Unsure

10

JM, a 38-year-old woman with a 16-year history of abdominal pain, bloating, and constipationMarried, 3 children, teacher, occasional ethanol, no

tobacco use

Pain eased by defecation

Feels like she does not completely evacuate her bowels; experiences severe straining, 2 bowel movements/week

Misses time from work due to symptoms

History of anxiety; currently on SSRI

No family history of organic GI disease; mother suffers from “constipation”

She has increased fiber intake, but this led to more bloating Tried exercise and dietary changes without success

Laxatives soften stool, but have no effect on abdominal pain, straining, or sense of complete evacuation

1. Past surgical history

2. History of migraine headaches

3. Discussion of life stresses and relation to symptoms

4. Discussion of physical and sexual abuse

5. Family history of digestive symptoms

?

Knowing she is currently taking an SSRI without success, what would be your next step?

1. Lab tests: CBC, CMP, TSH2. Pelvic examination3. Trial of FODMAP diet 4. Suggest switching from SSRI to TCA5. Colonoscopy with biopsy6. Psychiatry consultation to treat anxiety

?