Chronic Constipation: An Unresolved Problem for Many Patients

1
Chronic Constipation An Unresolved Problem
forMany Patients

• Charlene Prather, MD
• Division of Gastroenterology and Hepatology
• Saint Louis University School of Medicine

2
Presentation Objectives
C

• Definition of chronic constipation
• Epidemiology and resource utilization
• Review of available therapies and limitations
• Unmet medical need

3
Definition Causes of Chronic Constipation
C

• 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

4
Constipation Is a Constellation of Symptoms
C

• 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

5
Constipation Is More Than JustInfrequent Passage
of Stool
53
Constipation symptoms reported most often
n 1128
Sandler RS, et al. Dig Dis Sci. 198732841-845.
6
Reduced Stool Frequency Is Not the Most Commonly
Reported Symptom in Constipation
C
Constipation symptoms reported most often
Stewart (EPOC) 19991
Paré 20012
n 1476
n 1149
EPOC Epidemiology of constipation BM Bowel
movement. 1. Stewart WF, et al. Am J
Gastroenterol. 1999943530-3540. 2. Paré P, et
al. Am J Gastroenterol. 2001963130-3137.
7
Rome II Defines Functional Constipation Based on
Multiple Symptoms
C

• 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
• lt 3 defecations/wk
• Loose stools not present
• Insufficient criteria for IBS

gt 1/4 of defecations. Drossman DA, et al. In
Rome II The Functional Gastrointestinal
Disorders. 2000382-391.
8
Prevalence in the General Population
53
1. Stewart WF, et al. Am J Gastroenterol.
1999943530-3540. 2. Drossman DA, et al. Dig Dis
Sci. 1993381569-1580. 3. Harris Interactive
Study, Wave 2. Data on file. 4. Paré P, et al.
Am J Gastroenterol. 2001963130-3137.
9
Approximately 25 of Sufferers Seek Care
53
1. Stewart WF, et al. Am J Gastroenterol.
1999943530-3540. 2. Drossman DA, et al. Dig Dis
Sci. 1993381569-1580. 3. Harris Interactive
Study, Wave 2. Data on file. 4. Paré P, et al.
Am J Gastroenterol. 2001963130-3137.
10
Constipation Affects All Age Groups
53
N 1149
n 378
n 367
n 217
n 187
Canadian population. Paré P, et al. Am J
Gastroenterol. 2001963130-3137.
11
Epidemiology
C

• 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.
1999943530-3540. Paré P, et al. Am J
Gastroenterol. 2001963130-3137. Sandler RS, et
al. Dig Dis Sci. 198732841-845.
12
Profile of a Typical Chronic Constipation Patient
in My Practice
C

• Generally female
• Symptomatic for gt 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

13
Constipation Can Have a Negative Impact on
Quality of Life
C

• 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. OKeefe EA, et al. J Gerontol A Biol Sci Med
Sci. 199550M184-M189.2. Irvine EJ, et al. Am J
Gastroenterol. 2002971986-1993. 3. Koloski NA,
et al. Am J Gastroenterol. 20009567-71.
14
Constipation Significantly Impacts Healthcare
Utilization
C

• 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.gov 2. National Hospital Ambulatory Care
Survey, 2001. www.cdc.gov 3. Rantis PC Jr, et al.
Dis Colon Rectum. 199740280-286.
15
Goal of Therapy in Chronic Constipation
53

• 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

16
Medications Commonly Used for Constipation
53

• Fiber
• Laxatives
• Osmotic laxatives
• Stimulant laxatives
• Enemas or suppositories
• Miscellaneous

Adapted from Lembo A, et al. N Engl J Med.
20033491360-1368.
17
Efficacy of Current Treatments for Chronic
Constipation
53

• 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

Petticrew M, et al. Qual Health Care.
200110268-273. Jones MP, et al. Dig Dis Sci.
2002472222-2230. Rao SS. Gastroenterol Clin
North Am. 200332659-683.
18
Limitations of Current Treatmentsfor Constipation
C

• 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

Xing JH, et al. Dis Colon Rectum. 2001
Aug441201-1209. Garcia MC, et al. Tenn Med.
2002 Aug95334-336. Chaussade S, et al. Aliment
Pharmacol Ther. 2003 Jan17165-172. Riley SA,
et al. Br J Clin Pharmacol. 1992 Jul3440-46.
Gattuso JM, et al. Drug Saf. 1994 Jan1047-65.
Wald A. J Clin Gastroenterol. 200336386-89.
Duncan A, et al. Eur J Gastroenterol Hepatol.
200113599-601.
19
Physicians Believe Patient Satisfaction With
Current Therapies Is Low
C
Are your patients completely satisfied?
n 311
No82
Yes18
Not mutually exclusive.

• 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

Schiller LR, et al. Am Coll Gastroenterol. 2004,
abstract submitted.
20
Many Constipation Patients Are Not Satisfied With
Available Treatments
C
Are you completelysatisfied? 1
n 557
Yes53
No47
Not mutually exclusive.
1. Schiller LR, et al. Am Coll of Gastroenterol.
2004, abstract submitted. 2. Irvine EJ, et al. Am
J Gastroenterol. 2002971986-1993. 3. Ferrazzi
S, et al. Can J Gastroenterol. 200216159-164.
21
Chronic ConstipationA Condition in Need of a
Better Approach
C

• 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