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Transcript
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
Patient-practitioner relationship is the most
important component of the placebo effect in IBS
70
Adequate
Relief
Percentage
6
Global
Improvement
0
0
Quality of Life
Mean Change
12
Waiting List (n=87)
Limited (n=88)
Augmented (n=87)
0
Adapted from Kaptchuk, et
al BMJ 2008
Lubiprostone for IBS-C:
Overall response rate at week 12
12
TKGR-IBSC
5/23/2017
Pooled data from 2 Phase III studies
25%
***
17.9***
Placebo (n=387)
Lubiprostone
8 µg bid (n=780)
10.1
0
***p=0.001 vs placebo
Adapted from Drossman et al, APT 2009; 29: 329
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
14
TKGR-IBSC
5/23/2017
Hypnotherapy
• 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
Cochrane Database of Systematic Reviews 2007
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
17
Desipramine improves IBS symptoms
Composite symptom scale improvement
100
Placebo
**
73%
60%
47%
0
Intention-to-treat
analysis
Desipramine
n=431
49%
Per-protocol
analysis
**p=0.006 vs placebo
Modified from Drossman et al, Gastroenterology 2003; 125: 19–31
5/23/2017
Linaclotide for IBS-C
FDA endpoint
60%
***
Percent
response
33.6%*
Placebo (n=335)
Linaclotide
290 µg (n=312)
30%
21%
NNT = 7.9
0%
FDA endpoint: > 30% reduction in
abdominal pain AND increase >
1 CSBM for > 6 of 12 weeks
*p <
0.0001
Rao, et al. Am J Gastro 2012
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)
Low FODMAP Diet is more effective than
standard diet in IBS
82
% improved
8
0
6
0
86
85
81
61
50
49
Std (n=35)
49
4
0
FODMAP (n=39)
20
Bloating
P<0.002
Abd
Pain
P<0.02
Flatulence
P<0.001
Composite
Score
P<0.001
Staudacher HM, et al., J Hum Nutr Diet 2011 Oct; 24 (5): 487-95.
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?
Mechanism of
action
Cost
Additional
benefit
Rifaximin
FODMAP Diet
Decreases colonic
bacteria by killing
bugs
Decreases colonic
bacteria by reducing
dietary CHO
$910/42 tablets*
Cost of Food
Does not promote
weight loss
Might promote
weight loss
* www.drugstore.com, January 2014
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