IRRITABLE BOWEL SYNDROME

Arnold Wald, M.D., AGA-F

University of Wisconsin School of Medicine & Public Health, Madison, WI

1. A 35 y.o. teacher develops a diarrheal illness while on a trip to Mexico. Ciprofloxacin and loperamide are taken for 3 days but postprandial crampy abdominal pain, intermittent loose stools and bloating persist for 2 months. There is no weight loss, blood in the stools, arthritis, rash or fever but the patient complains of fatigue. Physical examination is normal, stool is hemoccult negative and CBC and stool studies are normal.

Which of the following statements about this condition is correct?

a) It is more likely to occur if the teacher is female and anxious

b) It is more likely to occur if the initial cause of the diarrhea was ST-producing E. coli 0157:H7

c) It is less likely to occur if the patient received antibiotics for the initial diarrheal illness

d) The diagnosis is best made with colonoscopy and biopsy of a normal appearing mucosa

POST-INFECTIOUS IBS

• 20% of IBS pts describe acute infectious prodrome

• Occurs in 5-25% after bacterial enteritis• Diarrhea predominant• No difference among pathogens (bacterial and

viral)• Greater likelihood in females, long duration of

diarrhea, and with use of antibiotics• Occurs in subjects with anxiety, depression

2. A 33 year old woman presents with a 3 year history of intermittent abdominal cramps, excessive bloating, intermittent diarrhea and no weight loss. Her physical examination is normal as is a CBC and C-reactive protein. Which of the following is correct?

a) She has an increased risk of celiac disease and should be tested with serology.

b) She has a 20% chance of having small intestinal bacterial overgrowth and should be tested with breath analysis.

c)She is likely to have no increase in either small intestine or colonic gas volume.

d)She is likely to have increased colonic methane gas production.

DIAGNOSTIC APPROACH TO PATIENT WITH IBS SYMPTOMS

(NO “ALARM SIGNS”)

CBC

Hemoccult

Routine colon cancer screening at ages > 50 yrs.

(ACG Functional GI Disorders Task Force, 2002)

Prevalence of Abnormal Serum Tests for Celiac Disease

IBS (n=492) Healthy Control (n=458)

AGA IgA 1.6% 1.8%

EMA 0.6% 0.4%

tTG IgA 1.2% 0.4%

DQ2 33% 39%

DQ8 16% 18%

Cash BD, et al. Gastroenterol 2011, 141: 1187-93

PROMETHEUS® IBS Diagnostic-NOT READY FOR CLINICAL USE!!

Performance of Validation Cohort

at 50% Disease Prevalence

(n=516)

Sensitivity 50%

Specificity 88%

Positive predictive value (PPV) 81%

Negative predictive value (NPV) 64%

Accuracy 70%

The selected validation cohort included 50% from patients with IBS, 36% from patients with non-IBS disorders (IBD, celiac disease, or functional GI disorders), and 14% healthy controls

Small Intestinal Bacterial Overgrowth and IBS

• Hypothesis is based upon poor methodology and erroneous conclusions.

• Original studies not reproduced by others using either similar and/or better methods. (Walters, Posserud)

• Use of antibiotics to suppress colon bacteria effective in some patients with IBS.

3. Which of the following treatments for IBS exhibits the greatest benefit over placebo in randomized controlled trials?

a) Lubiprostone

b) Rifaximin

c) A good physician-patient relationship

d) Hypnosis

6

0

Global Improvement

70

0

Adequate Relief

Pe

rce

nta

ge

12

0

Quality of Life

Me

an

Ch

an

ge

Waiting List (n=87)

Limited (n=88)

Augmented (n=87)

Adapted from Kaptchuk, et al BMJ 2008

Patient-practitioner relationship is the most important component of the placebo effect in IBS

Lubiprostone for IBS-CLubiprostone for IBS-C: : Overall response rate at week 12Overall response rate at week 12

04/19/2312 TKGR-IBSC

Adapted from Drossman et al, APT 2009; 29: 329

***p=0.001 vs placebo

Placebo (n=387)

Lubiprostone

8 µg bid (n=780)

***

10.1

17.9***

0

25%

Pooled data from 2 Phase III studies

Rifaximin: Global Improvement

Measure Outcomes

Response rates (%) Weight Therapeutic Gain

NNT

Rifaximin Placebo

Sharara 27.0 9 1.4% 18% 5.6

Pimentel 32.5 9 1.6% 23.5% 4.3

Lembo 52.3 44.2 25.2% 8.1% 12.3

Target 1 40.8 31.2 34.9% 9.6% 10.4

Target 2 40.6 32.2 36.8% 8.4% 11.9

Overall 43.3 34.2 100% 9.1% 11.0

• Gut-directed hypnotherapy effective in improving IBS symptoms

• 6 RCTs; patients refractory to standard management – reduces anxiety and improves symptom control

in majority of patients with refractory IBS

Cochrane review of 4 randomized clinical studies (n=147)– hypnotherapy improved abdominal pain and overall IBS symptoms

– results should be interpreted with caution due to poor methodological quality and small sample sizes

HypnotherapyHypnotherapy04/19/2314 TKGR-IBSC

4. A 44 y.o. woman with diarrhea predominant IBS is started on nortriptyline 10 mg daily but she complains of fatigue, disorientation and palpitations which persist after 10 days. Her IBS symptoms are unchanged.

The most appropriate course of action is:

a) Continue the drug for another 2 weeks as she will gradually adapt to side effects

b) Discontinue the drug; start linaclotide 145 mcg daily

c) Discontinue the drug; refer her for cognitive behavioral therapy

d) Discontinue the drug; prescribe desipramine 10 mg daily

Psychotropic agents in IBS

• Antidepressants in small doses improve functional pain independently of psychotropic properties

• Known side effects can be useful in IBS

• SSRIs better than placebo for global improvement

• TCAs better than placebo for abdominal pain and symptom scores

Desipramine improves IBS symptomsDesipramine improves IBS symptoms17

Modified from Drossman et al, Gastroenterology 2003; 125: 19–31

n=431

**

**p=0.006 vs placebo

Composite symptom scale improvement100

0

47%

60%49%

73%

Placebo

Desipramine

Intention-to-treatanalysis

Per-protocolanalysis

Linaclotide for IBS-CLinaclotide for IBS-C

04/19/23

Rao, et al. Am J Gastro 2012

NNT = 7.9

*p < 0.0001

Placebo (n=335)

Linaclotide

290 µg (n=312)

***

21%

33.6%*

0%

60%

FDA endpoint

30%

Percentresponse

FDA endpoint: > 30% reduction in abdominal pain AND increase > 1 CSBM for > 6 of 12 weeks

5. A 30 y.o. normal weight woman presents because of intermittent diarrhea, bloating, flatulence and abdominal discomfort of many years duration. Her physical examination is normal, as is a CBC and sedimentation rate. She has tried simethicone, Gas X and Beano ® with no improvement. She does not smoke, consume milk products or drink carbonated beverages.

Which of the following would be the most cost effective approach?

a) Rifaxamin

b) FODMAP restricted diet

c) Citalopram

d) Mediterranean diet

FODMAPs (Fermentable oligo-, di- and monosaccharides and polyols)

• Fructans (onions, wheat, artichokes)• Galactans (legumes, cabbage, Brussel

sprouts)• Lactose• Sorbitol• Xylitol• Mannitol• Sucralose (Splenda)

20

40

60

80

% im

pro

ved

Bloating

P<0.002

Abd Pain

P<0.02

Flatulence

P<0.001

Composite Score

P<0.001

Std (n=35)

FODMAP (n=39)

Low FODMAP Diet is more effective than standard diet in IBS

Staudacher HM, et al., J Hum Nutr Diet 2011 Oct; 24 (5): 487-95.

49

82

61

85

50

81

49

86

Low FODMAP Diet Reduces Symptoms of IBS

From Halmos et al, Gastro 2014

Rifaximin: Bloating

Author Weight OR 95%CI

P value

Pimentel 2.5% 3.81 1.39,10.45 0.0095

Lembo 26% 1.30 0.87,1.95 0.1975

Target 1 33.9% 1.64 1.18,2.29 0.0035

Target 2 37.5% 1.38 1.07,2.05 0.0140

Overall 100% 1.55 1.27,1.89 <0.001

Favors Placebo Favors Rifaximin

TREATMENT OF BLOATING AND IBS: Diet or Antibiotic?

* www.drugstore.com, January 2014

Rifaximin FODMAP Diet

Mechanism of action

Decreases colonic bacteria by killing

bugs

Decreases colonic bacteria by reducing

dietary CHO

Cost $910/42 tablets* Cost of Food

Additional benefit

Does not promote weight loss

Might promote weight loss

References

1. ACG IBS Task Force, An evidence-based position statement on the management of IBS. Am J Gastroenterol 2009;104:S1-35.

2. Ford AC, Vandvik PO. Irritable bowel syndrome. Clin Evid(online) 2012 Jan 6 pii0410