CM-1CM-1

Chronic Constipation: An Unresolved Problem for

Many Patients

Chronic Constipation: An Unresolved Problem for

Many Patients

Charlene Prather, MD

Division of Gastroenterology and Hepatology

Saint Louis University School of Medicine

Charlene Prather, MD

Division of Gastroenterology and Hepatology

Saint Louis University School of Medicine

CM-2CM-2

Presentation ObjectivesPresentation Objectives

Definition of chronic constipation

Epidemiology and resource utilization

Review of available therapies and limitations

Unmet medical need

Definition of chronic constipation

Epidemiology and resource utilization

Review of available therapies and limitations

Unmet medical need

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CM-3CM-3

Definition: Causes of Chronic ConstipationDefinition: Causes of Chronic Constipation

Secondary– Drug induced – Metabolic factors– Comorbid conditions

Primary– Impaired colonic transit/motility

• Altered neuroenteric function and reflexes• Failure of muscular apparatus

– Ineffective defecation (functional outlet obstruction)• Pelvic dyssynergia and anismus

– Normal transit constipation

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CM-4CM-4

Constipation Is a Constellation of SymptomsConstipation Is a Constellation of Symptoms

Most commonly reported symptoms

– Hard, lumpy stools

– Increased straining

– Infrequent bowel movements

– Sensation of incomplete evacuation

– Bloating/fullness Chronic constipation

– More persistent than intermittent or episodic

– Several months duration

Most commonly reported symptoms

– Hard, lumpy stools

– Increased straining

– Infrequent bowel movements

– Sensation of incomplete evacuation

– Bloating/fullness Chronic constipation

– More persistent than intermittent or episodic

– Several months duration

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CM-5CM-5

52

44

3432

20 19

11

0

10

20

30

40

50

60

Straining Hard stools

Want to but can't

Infrequentstools

Abdominaldiscomfort

Haven'tfinished

Excesstoilet time

Pa

tie

nts

, %

Sandler RS, et al. Dig Dis Sci. 1987;32:841-845.

n = 1128

Constipation Is More Than JustInfrequent Passage of StoolConstipation Is More Than JustInfrequent Passage of Stool

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Constipation symptoms reported most often

CM-6CM-6Reduced Stool Frequency Is Not the Most Commonly Reported Symptom in Constipation

Reduced Stool Frequency Is Not the Most Commonly Reported Symptom in Constipation

13

26

32

36

65

83

0 20 40 60 80 100

< 3 BM/wk

Abdominal bloating ≥ 6 days

Press on abdomen

Abdominal discomfort

Unsuccessful BM

Incomplete BM

Patients, %

28

36

37

39

54

72

81

0 20 40 60 80 100

Press on anus

< 3 BM/wk

Abdominal bloating

Stool cannot pass

Incomplete evacuation

Hard stool

Straining

Patients, %

EPOC = Epidemiology of constipation; BM = Bowel movement.1. Stewart WF, et al. Am J Gastroenterol. 1999;94:3530-3540.2. Paré P, et al. Am J Gastroenterol. 2001;96:3130-3137.

Stewart (EPOC) 19991 Paré 20012

n = 1476 n = 1149

Constipation symptoms reported most often

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CM-7CM-7

Rome II Defines Functional Constipation Based on Multiple SymptomsRome II Defines Functional Constipation Based on Multiple Symptoms

Rome II diagnostic criteria for functional constipation At least 12 wk, which need not be consecutive, over the past

12 months of 2 or more of

– Straining*

– Lumpy or hard stools*

– Sensation of incomplete evacuation*

– Sensation of anorectal obstruction/blockage*

– Manual maneuvers to facilitate defecation*

– < 3 defecations/wk Loose stools not present Insufficient criteria for IBS

Rome II diagnostic criteria for functional constipation At least 12 wk, which need not be consecutive, over the past

12 months of 2 or more of

– Straining*

– Lumpy or hard stools*

– Sensation of incomplete evacuation*

– Sensation of anorectal obstruction/blockage*

– Manual maneuvers to facilitate defecation*

– < 3 defecations/wk Loose stools not present Insufficient criteria for IBS

* > 1/4 of defecations.Drossman DA, et al. In: Rome II: The Functional Gastrointestinal Disorders. 2000:382-391.

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CM-8CM-8

Prevalence in the General PopulationPrevalence in the General Population

1. Stewart WF, et al. Am J Gastroenterol. 1999;94:3530-3540.2. Drossman DA, et al. Dig Dis Sci. 1993;38:1569-1580.3. Harris Interactive Study, Wave 2. Data on file. 4. Paré P, et al. Am J Gastroenterol. 2001;96:3130-3137.

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Population n Criteria

Prevalence, n (%)

US1 10,018 Rome I 461 (4.6)

US2 5430 Rome I 195 (3.6)

US3 15,183 Rome II

2429 (16)

Canada4 1149 Rome II

171 (14.9)

CM-9CM-9

Approximately 25% of Sufferers Seek CareApproximately 25% of Sufferers Seek Care

1. Stewart WF, et al. Am J Gastroenterol. 1999;94:3530-3540.2. Drossman DA, et al. Dig Dis Sci. 1993;38:1569-1580.3. Harris Interactive Study, Wave 2. Data on file. 4. Paré P, et al. Am J Gastroenterol. 2001;96:3130-3137.

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Population n Criteria

Prevalence, n (%)

Sought care,%

US1 10,018 Rome I 461 (4.6) NA

US2 5430 Rome I 195 (3.6) 22

US3 15,183 Rome II

2429 (16) 24

Canada4 1149 Rome II

171 (14.9) 26

CM-10CM-10

Constipation Affects All Age GroupsConstipation Affects All Age Groups

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Canadian population.Paré P, et al. Am J Gastroenterol. 2001;96:3130-3137.

0

5

10

15

20

25

18 - 34 35 - 49 50 - 64 > 64

Age group, yr

Co

nst

ipat

ed,

%

Rome I

Rome II

N = 1149

n = 378 n = 367 n = 217 n = 187

CM-11CM-11

EpidemiologyEpidemiology

Chronic constipation is common

Slightly more common in women

– F/M ratio = range 1.3 to 2.5

Affects all age groups

Chronic constipation is common

Slightly more common in women

– F/M ratio = range 1.3 to 2.5

Affects all age groups

Stewart WF, et al. Am J Gastroenterol. 1999;94:3530-3540.Paré P, et al. Am J Gastroenterol. 2001;96:3130-3137.Sandler RS, et al. Dig Dis Sci. 1987;32:841-845.

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CM-12CM-12

Profile of a Typical Chronic Constipation Patient in My PracticeProfile of a Typical Chronic Constipation Patient in My Practice

Generally female

Symptomatic for > 10 yr

Majority have tried lifestyle changes, fiber, and OTC laxatives prior to seeking care

Manages condition with multiple therapies

Most often referred by a primary care physician

Copes with condition, but is not completely satisfied

Generally female

Symptomatic for > 10 yr

Majority have tried lifestyle changes, fiber, and OTC laxatives prior to seeking care

Manages condition with multiple therapies

Most often referred by a primary care physician

Copes with condition, but is not completely satisfied

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CM-13CM-13

Constipation Can Have a Negative Impact on Quality of LifeConstipation Can Have a Negative Impact on Quality of Life

In Olmstead County, Minnesota, people with CC reported significant impairment in QoL on SF-36 scale (n = 126)1

In Canada, people with self-reported or Rome II constipation had significantly worse SF-36 scores than the normal population (n = 472)2

In Australia, people with constipation had significantly worse SF-12 scores on both mental and physical scales (n = 227)3

In Olmstead County, Minnesota, people with CC reported significant impairment in QoL on SF-36 scale (n = 126)1

In Canada, people with self-reported or Rome II constipation had significantly worse SF-36 scores than the normal population (n = 472)2

In Australia, people with constipation had significantly worse SF-12 scores on both mental and physical scales (n = 227)3

1. O’Keefe EA, et al. J Gerontol A Biol Sci Med Sci. 1995;50:M184-M189.2. Irvine EJ, et al. Am J Gastroenterol. 2002;97:1986-1993. 3. Koloski NA, et al. Am J Gastroenterol. 2000;95:67-71.

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CM-14CM-14

Constipation Significantly Impacts Healthcare UtilizationConstipation Significantly Impacts Healthcare Utilization

5.7 million constipation-related outpatient visits annually1,2

– 4.1 million physician office-based visits

– 991,000 emergency room visits

– 587,000 hospital outpatient visits

$2752/patient for tertiary care evaluation3

5.7 million constipation-related outpatient visits annually1,2

– 4.1 million physician office-based visits

– 991,000 emergency room visits

– 587,000 hospital outpatient visits

$2752/patient for tertiary care evaluation3

1. National Ambulatory Medical Care Survey, 2001. www.cdc.gov2. National Hospital Ambulatory Care Survey, 2001. www.cdc.gov3. Rantis PC Jr, et al. Dis Colon Rectum. 1997;40:280-286.

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CM-15CM-15

Goal of Therapy in Chronic ConstipationGoal of Therapy in Chronic Constipation

The goal of therapy is to improve GI function in order to provide relief of key symptoms:

– Straining

– Hard/lumpy stools

– Feeling of incomplete evacuation

– Infrequent bowel movements

– Bloating/fullness

The goal of therapy is to improve GI function in order to provide relief of key symptoms:

– Straining

– Hard/lumpy stools

– Feeling of incomplete evacuation

– Infrequent bowel movements

– Bloating/fullness

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CM-16CM-16

Medications Commonly Used for ConstipationMedications Commonly Used for Constipation

Fiber

Laxatives

– Osmotic laxatives

– Stimulant laxatives

Enemas or suppositories

Miscellaneous

Fiber

Laxatives

– Osmotic laxatives

– Stimulant laxatives

Enemas or suppositories

Miscellaneous

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Adapted from Lembo A, et al. N Engl J Med. 2003;349:1360-1368.

CM-17CM-17

Efficacy of Current Treatments for Chronic Constipation Efficacy of Current Treatments for Chronic Constipation

Variable treatment responses

For the constellation of constipation symptoms, efficacy not evaluated or demonstrated with most agents

Most agents indicated for ≤ 2 wk of treatment

Variable treatment responses

For the constellation of constipation symptoms, efficacy not evaluated or demonstrated with most agents

Most agents indicated for ≤ 2 wk of treatment

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Petticrew M, et al. Qual Health Care. 2001;10:268-273. Jones MP, et al. Dig Dis Sci. 2002;47:2222-2230. Rao SS. Gastroenterol Clin North Am. 2003;32:659-683.

CM-18CM-18

Limitations of Current Treatmentsfor ConstipationLimitations of Current Treatmentsfor Constipation Worsening of some constipation symptoms

– Bloating and gas– Cramping, abdominal pain/colic

Development of complications – Diarrhea, hypovolemia – Metabolic disturbances

Other adverse effects– Interference with concomitant drug absorption– Structural changes in gut mucosa– Abuse potential (dependency)

Diminished therapeutic effect over time

Worsening of some constipation symptoms– Bloating and gas– Cramping, abdominal pain/colic

Development of complications – Diarrhea, hypovolemia – Metabolic disturbances

Other adverse effects– Interference with concomitant drug absorption– Structural changes in gut mucosa– Abuse potential (dependency)

Diminished therapeutic effect over time

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Xing JH, et al. Dis Colon Rectum. 2001 Aug;44:1201-1209. Garcia MC, et al. Tenn Med. 2002 Aug;95:334-336. Chaussade S, et al. Aliment Pharmacol Ther. 2003 Jan;17:165-172. Riley SA, et al. Br J Clin Pharmacol. 1992 Jul;34:40-46. Gattuso JM, et al. Drug Saf. 1994 Jan;10:47-65. Wald A. J Clin Gastroenterol. 2003;36:386-89. Duncan A, et al. Eur J Gastroenterol Hepatol. 2001;13:599-601.

CM-19CM-19

Physicians Believe Patient Satisfaction With Current Therapies Is LowPhysicians Believe Patient Satisfaction With Current Therapies Is Low

YesYes18%18%

Are your patients completely satisfied?

NoNo82%82%

Schiller LR, et al. Am Coll Gastroenterol. 2004, abstract submitted.

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n = 311

• 60% of physicians agreed that they do not have adequate products

• 90% of physicians wanted better treatment options

• Physicians cited “frustration with current treatments” one of the top 3 reasons patients state for seeking care

Reasons for dissatisfaction*

Efficacy 93%Safety/side effects 57%Other (ie, taste, compliance) 27%

*Not mutually exclusive.

CM-20CM-20

Many Constipation Patients Are Not Satisfied With Available TreatmentsMany Constipation Patients Are Not Satisfied With Available Treatments

Reasons for dissatisfaction* 1

Efficacy 82%Safety/side effects 16%Other (ie, taste, compliance) 17%

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1. Schiller LR, et al. Am Coll of Gastroenterol. 2004, abstract submitted.2. Irvine EJ, et al. Am J Gastroenterol. 2002;97:1986-1993. 3. Ferrazzi S, et al. Can J Gastroenterol. 2002;16:159-164.

*Not mutually exclusive.

YesYes53%53%

Are you completelysatisfied? 1

NoNo47%47%

n = 557

CM-21CM-21

Chronic Constipation:A Condition in Need of a Better ApproachChronic Constipation:A Condition in Need of a Better Approach

Characterized by a constellation of symptoms

High resource utilization and significant negative impact on patients’ lives

Current pharmacologic agents have limitations Many patients are not satisfied with available

therapies Better treatment options are needed

Characterized by a constellation of symptoms

High resource utilization and significant negative impact on patients’ lives

Current pharmacologic agents have limitations Many patients are not satisfied with available

therapies Better treatment options are needed

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