Transcript Slide 1

Learning Objectives
• Accurately recognize overactive bladder (OAB), with urgency
as the core symptom, in the context of other urinary symptoms
that are commonly encountered in men and women
• Confidently assess important measures like symptom severity
and health-related quality of life (HRQOL) and use this
information for patient management
• Apply behavioral and lifestyle modifications to treatment
strategies using an individualized and patient-centered
approach to OAB
• Understand the current first-line treatments for OAB in both
men and women
• Employ a patient-centered treatment strategy that explores the
benefits of dosing antimuscarinics to obtain a balance between
efficacy and tolerability
Premeeting Survey
•
True or False: The core symptom of OAB is
urgency.
1. True
2. False
?
Premeeting Survey
•
Which of the following are NOT considered
comorbidities in patients with OAB?
1.
2.
3.
4.
Falls and fractures
Urinary tract infections (UTIs)
Skin infections
Kidney stones
?
Premeeting Survey
•
True or False: Using a flexible-dosing regimen of
antimuscarinics results in improved efficacy and
patient satisfaction.
1. True
2. False
?
Overactive Bladder: Impact
Matt T. Rosenberg, MD
MidMichigan Health Centers
Jackson, MI
ICS Definition of Overactive Bladder
• A symptom syndrome suggestive of lower urinary
tract dysfunction1,2
• Urgency, with or without urge incontinence, usually
with frequency and nocturia1,2
• In absence of metabolic or pathologic conditions1,2
1Abrams
ICS: International Continence Society
P, et al. Neurourol Urodyn. 2002;21:167-178.
AJ, et al. Urology. 2002;60(5 suppl 1):7-12.
2 Wein
Overactive Bladder Definitions
Urgency1,2
Sudden compelling desire to pass urine that is difficult to defer
Frequency1,2
Patient considers that he/she voids too often by day
Normal is < 8 times per 24 hours
Nocturia1,2
Waking to urinate during sleep hours
Considered a clinical problem if frequency is greater than twice a night
Urge urinary
incontinence (UUI)1
Involuntary leakage accompanied by or immediately preceded by urgency
OAB “wet”1,2
OAB with UUI
OAB “dry”2
OAB without UUI
Warning time3
Time from first sensation of urgency to voiding
1Abrams
P, et al. Neurourol Urodyn. 2002;21:167-178.
AJ, et al. J Urol. 2006;175(3 pt 2):S5-S10.
3Zinner N, et al. Int J Clin Pract. 2006;60:119-126.
2Wein
Healthy Bladder Versus Overactive
Bladder
•
•
•
•
Holds 300-500 cc
Empties < 8 times per day
Holds at night
After gradual filling, urge is
felt
• Empties > 8 times per day
• Empties > 2 times per night
• Has urgency (sudden
compelling desire to void
that is difficult to defer)
Pfisterer MH-D, et al. Neurourol Urodyn. 2007;26:356-361.
Wein AJ. Am J Manag Care. 2000;6(11 suppl):S559-S564.
Wein AJ, et al. J Urol. 2006;175(3 pt 2):S5-S10.
OAB Symptoms Are as Prevalent in
Men as in Women and Increase
With Age
Population-based prevalence studies:
40
Prevalence (%)
35
30
25
Comparison of data from the SIFO study (1997)*1
and the EPIC study (2005)†2
Men (SIFO 1997)
16.6
Women (SIFO 1997)
Men (EPIC 2005)
Women (EPIC 2005)
11.8
20
15
10
5
0
18-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69
> 70
Age (years)
SIFO: Sifo/Gallup telephone survey
* N = 16,776 interviews (6 European countries)
† N = 19,165 interviews (4 European countries and Canada)
1Milsom
2Irwin
I, et al. BJU Int. 2001;87:760-766.
DE, et al. Eur Urol. 2006;50:1306-1314.
Urgency Leading to Urgency
Incontinence: More Prevalent in
Women
Women with OAB
Men with OAB
(n = 463)
(n = 401)
With UUI
16%
With UUI
55%
Without UUI
45%
National Overactive Bladder Evaluation Study
Without UUI
84%
Stewart WF, et al. World J Urol. 2003;20:327-336.
Overcoming Barriers in OAB: Forming
an Accurate Diagnosis
Patients Suffer Needlessly
From OAB
• OAB negatively impacts
QOL:
–
–
–
–
–
–
–
–
Emotional well-being
Social relationships
Productivity
Physical functioning
Anxiety
Hostility
Depression
Avoid activities like travel
Patients Would Rather
Cope With OAB Than Seek
Help Due to:
• Fear of embarrassment
• Fear resulting from
misconceptions
• Differences in perception:
– Symptom severity
– Degree of bother
– Willingness to seek treatment
Khullar V, et al. Urology. 2006;68(2 suppl):38-48.
Dmochowski RR, et al. Curr Med Res Opin. 2007;23:65-76.
OAB Symptoms Negatively Affect
Patients
100
Percent of patients
A lot
Moderately
A little
Omitted or not applicable
80
60
59.3
49.2
47.3
40
38.1
33.5
32.5
20.5
16.7
20
7.2
1.0
31.3
30.3
14.8
2.4
10.1
5.6
0
Frequency
Nocturia
HRQOL assessed with King’s Health Questionnaire
N = 2878
Urgency
UUI
Sand P, et al. BJU Int. 2007;99:836-844.
Percentage of women
(agree strongly or completely)
Women Prefer Clinicians to Initiate
Discussion About Urinary
Symptoms
50
40
43
37
35
33
Total
(n = 1046)
SUI
(n = 386)
UUI
(n = 271)
30
20
10
0
MUI
(n = 389)
• Participant question: “I would be more comfortable discussing
urinary symptoms if my health care provider brought up the
topic.”
SUI: stress urinary incontinence
MUI: mixed urinary incontinence
MacDiarmid S, et al. Curr Med Res Opin. 2005;21;1413-1421.
Percentage of patients
Look for Comorbidities of OAB
28.0
30
25.3
25
OAB
Control
20
16.1
P < 0.0001
15
10.5
8.4
10
5
4.7
1.8
3.9
4.9
2.3
0
Vulvovaginitis Skin infections
Depression
UTIs
Falls and
fractures
• These conditions were 2.8 times more likely to occur in
patients with OAB compared to controls (95% CI, 2.6-2.9):
– Adjusted for neurologic conditions, diuretic use, potentially
inappropriate drug use, and UTI risk factors
11,556 adult patients with OAB and 11,556
controls matched on propensity score
Adapted from Darkow T, et al. Pharmacotherapy. 2005;25:511-519.
How Do You Approach a
Conversation About Urinary
Problems Like OAB?
?
1. I ask 1 or more questions like, “Do you have urinary
problems?”
2. I let the patient bring it up
3. I use a questionnaire
4. I do not routinely ask about urinary problems
How to Optimally Obtain a Patient
History:
First Line of Questioning
• Do you have urinary problems?1,2
• How much do the symptoms bother you?
• Do you want medication for your problems?
1Lavelle
JP, et al. Am J Med. 2006;119(3 suppl 1):37-40.
MT, et al. Cleve Clin J Med. 2005;72:149-156.
2Rosenberg
How to Optimally Obtain a Patient
History:
Second Line of Questioning
How are you handling
your urinary symptoms?
What is your most distressing symptom?
How long have you experienced these symptoms?
What is your fluid intake?
What have you tried to solve your problems?
Urgency
• Do you have to rush to go to the toilet?
• Do you have to urinate IMMEDIATELY?
Frequency
• Do you feel that you urinate too often during the day?
Nocturia
• Do you have to get up during the night to urinate?
• Is it the urge to urinate that wakes you?
UUI
• When you feel the urge to urinate, do you have leaks
or wetting accidents?
Rosenberg MT, et al. Cleve Clin J Med. 2005;72:149-156.
Irwin DE, et al. Eur Urol. 2006;50:1306-1314.
Marschall-Kehrel D, et al. Urology. 2006;68(2 suppl):29-37.
How to Optimally Obtain a Patient
History:
Elements of the Examination
• Now that the urinary problem is identified, inquire
about:
–
–
–
–
–
Lower urinary tract symptoms (LUTS)
Medical and surgical history
Medications
Focused physical examination
Laboratory examinations and/or tests:
• Voiding diary, pad test
Lavelle JP, et al. Am J Med. 2006;119(3 suppl 1):37-40.
Rosenberg MT, et al. Cleve Clin J Med. 2005;72:149-156.
Clinical Practice
Recommendation
• Practice recommendation:
– Patient history in combination with pad tests and urinary diaries is
effective in diagnosing OAB
• Evidence-based source:
– Health Technology Assessment
• Web site of supporting evidence:
– http://www.ncchta.org/fullmono/mon1006.pdf
• Strength of evidence:
– Of 6009 papers, 121 were relevant for inclusion in the review:
• Comparison of 2 or more assessment/diagnostic techniques
– Simple investigations (eg, pad test and diary) may offer useful
information on severity
– Combined with history, process may provide sufficient information to
commence primary care interventions (which are low cost and low risk)
Case Study 1: Carol
Presentation
• Carol, aged 55 years, has been a long-term patient of
yours and presents to your office to check on her
hypertension and get a new prescription
• She seems hesitant to leave after the examination
and you question her on other troubling symptoms
• She admits to experiencing OAB symptoms with
great bother:
– Frequency has increased in the past 6 months
– Nocturia
• Medical history:
– Previously treated for depression and UTIs
– Hypertension treated with diuretic and calcium channel blocker
– Atrophic vaginitis testing was unremarkable
What Is Your Initial
Approach to Treating Carol?
1. Behavioral modifications
2. Pharmacotherapy
3. Combination of behavioral modifications and
pharmacotherapy
4. I ask the patient for her treatment goals and
preference first
5. I do not treat OAB
?
Behavioral Modifications Are a
Good Starting Point
• Bladder training: scheduled voiding/voiding
deferment1,2
• Pelvic floor exercises1-4:
–
–
–
–
Can be easily performed at home with no equipment needed
Not associated with significant adverse events
Significant impact in women with UUI and MUI
Evidence for men lacking
• Significantly higher cure rates and satisfaction
associated with combined bladder training and
pelvic floor exercises than either therapy alone4
1Christofi
N, et al. Menopause Int. 2007;13:154-158.
DK. Am J Nurs. 2002;102:36-45.
3Burgio KL. J Am Acad Nurse Pract. 2004;16(10 suppl):4-7.
4Milne JL. J Wound Ostomy Continence Nurs. 2008;35:93-101.
2Newman
Clinical Practice
Recommendation
• Practice recommendation:
– Behavioral therapy improves symptoms of UUI and MUI
• Evidence-based source:
– National Guideline Clearinghouse
• Web site of supporting evidence:
– http://www.guideline.gov/summary/summary.aspx?doc_id=1093
1&nbr=005711&string=incontinence
• Strength of evidence:
– Level A
– Can be recommended as a noninvasive treatment in many
women
Lifestyle Modifications in OAB:
Current Evidence Is Sparse and
Inconsistent
• Caffeine reduction dose dependent1:
– Affects patients consuming ≥ 400 mg caffeine or 2.5 cups of coffee
• Weight loss1:
– Significant reduction in UUI reported:
• No data in men or in OAB dry or moderately overweight patients
• Adjusting fluid intake1,2:
– Greater impact than caffeine restriction
– For significant improvement in urgency, frequency, and nocturia
episodes, modify fluid input by 25% (goal: 1500-2400 mL/day)
• Few data for smoking cessation and regulation of
bowel function2
1Milne
JL. J Wound Ostomy Continence Nurs. 2008;35:93-101.
2Newman DK, et al. Am J Nurs. 2002;102:36-45.
Case Study 1: Carol
Treatment
• Low-dose antimuscarinic with daily dosing
• Take diuretic before bedtime to improve nocturia
• Behavioral modifications
OAB in Female Patients
Differential Diagnosis of Symptoms
in Women With OAB
Women
UTI
Bladder cancer
Diabetes
Multiple sclerosis
SUI
Recent pelvic surgery
Neurogenic bladder
Prolapse
Urethral obstruction
Atrophic vaginitis
Postsurgical incontinence
Rosenberg MT, et al. Cleve Clin J Med. 2007;74(suppl 3):S21-S29.
ICI Management of Incontinence
in Women
Incontinence
on physical
activity
Incontinence
with mixed
symptoms
Incontinence
with
urgency/frequency
Evaluation
SUI
MUI
UUI
Pelvic floor muscle training
Bladder retraining
Treat most
bothersome
symptoms for MUI
Antimuscarinics
ICI: International Consultation on Incontinence
Adapted from Kirby M, et al. Int J Clin Pract. 2006;60:1263-1271.
Treatment Strategies and
Pharmacotherapy for OAB
David R. Staskin, MD
New York Presbyterian Hospital
New York, NY
Treatment Goals for OAB
Eliminate or improve UUI
Reduce urgency - frequency - incontinence - nocturia
Improvement in warning time
Ensure treatment compliance for multiple long-term benefits:
- Consider appropriate dose, comorbidities, cost, and improved QOL
Consensus with the patient’s treatment expectations
Hegde SS. Br J Pharmacol. 2006;147(suppl 2):S80-S87.
Staskin DR, et al. Am J Med. 2006;119(3 suppl 1):9-15.
Cardozo L, et al. J Urol. 2005;173:1214-1218.
Patient and Physician Expectations
Overall Expectations
of Treatment1
Physicians
Patients
Complete Cure
3.2%
17%
Improved QOL
85.9%
43%
Tailor to2:
Not tailoring treatment may lead to2:
•
•
•
•
•
•
•
•
•
•
•
Environment
Expectations
Lifestyle
Age
Health
Disillusionment
Avoidable adverse events
Unneeded use of time and resources
Harmful and unnecessary surgery
Morbidity/mortality
Worsening symptoms
1Robinson
D, et al. Int Urogynecol J Pelvic Floor Dysfunct. 2007;18:273-279.
2Cardozo L. BJU Int. 2007;99(suppl 3):1-7.
Clinical Practice
Recommendation
• Practice recommendation:
– Antimuscarinics significantly reduce OAB symptoms
• Evidence-based source:
– Cochrane Database of Systematic Reviews
• Web site of supporting evidence:
– http://www.cochrane.org/reviews/en/ab003781.html
• Strength of evidence:
– 61 trials included in the review
– The use of anticholinergic drugs for OAB results in statistically
significant improvements in symptoms
Symptom-Based OAB Management
Percent of patients
Patient perception of improvement in overall bladder condition at week 12*1
Major improvement
100
80
Minor improvement
Questionnaires used:
28.3
60
29.7
29.9
24.9
28.4
48.3
48.6
49.7
50.4
Frequency
(day)
Nocturia
UUI
Total
40
58.0
20
OAB symptom questionnaire
(OAB-q)
American Urological Association
Symptom Index
Patient Perception of Bladder
Condition (PPBC)
0
Urgency
863 patients from 82 primary care and 16 obstetric/gynecology offices1,2
•
•
OAB symptoms ≥ 3 months; at least moderately bothered by most bothersome symptom
69% of patients had ≥ 1 comorbid condition; none of the patients had retention requiring
catheterization
* IMPACT: tolterodine extended release (ER) 12-week, openlabel study
1Roberts
2Elinoff
R, et al. Int J Clin Pract. 2006;60:752-758.
V, et al. Int J Clin Pract. 2006;60:745-751.
Pros and Cons: Antimuscarinics
PROS
CONS
Only approved treatments with
grade A recommendation
Physiology/uropharmacology
still does not provide ideal agent
Extensive literature has
demonstrated efficacy and
improved QOL
Adherence to therapy is low
Data available from large-scale,
randomized controlled trials
High placebo rates
Alternative surgical treatments
limited by morbidity and cost
Response to behavioral therapies
Good tolerability
Anticholinergic side effects
Adapted from Chapple C, et al. Eur Urol. 2008;54:226-230.
Potential Adverse Events,
Contraindications, and Drug
Interactions of Antimuscarinics
Most common side effects
Dry mouth1,2
Constipation1,2
Blurred vision1,2
Rare/potential adverse events
Sedation, cognitive effects2,3
Drowsiness, headache4
Cardiac adverse effects (QT prolongation)4
Heat prostration (decreased sweating)4
Contraindications
Urinary or gastric retention4
Uncontrolled narrow-angle glaucoma4
Drug interactions
Antidepressants*2,3
Polypharmacy in the elderly2
CYP3A4 inhibitors†3,5
Diuretic effect of alcohol2
1Steers WD. Urol Clin North Am. 2006;33:475-482.
* eg, paroxetine (SSRI) shares CYP2D6
2Erdem N, et al. Am J Med. 2006;119(3 suppl 1):29-36.
liver metabolism with darifenacin
3Staskin DR. Drugs Aging. 2005;22:1013-1028.
† eg, ketoconazole, fluoxetine (SSRI)
4Physicians’ Desk Reference. 62nd ed. Montvale, NJ: Thomson PDR; 2008.
5Swart PJ, et al. Basic Clin Pharmacol Toxicol. 2006;99:33-36.
SSRI: selective serotonin reuptake inhibitor
Adverse Events Decline Over Time*
Percent of patients
50
40
Consistent finding across long-term studies for OAB:
adverse events are most common within 3 months of therapy
and decline thereafter
30
20
Dry mouth
Constipation
10
0
0 to 3
> 3 to 6
> 6 to 9
> 9 to 12
> 12 to
15
> 15 to
18
> 18 to
21
> 21 to
24
> 24
Treatment duration (months)
N = 716
* 24-month, noncomparative, darifenacin, open-label extension study
Haab F, et al.
BJU Int. 2006;98:1025-1032.
Enhanced Therapeutic Effects
With Combined Pharmacologic
and Behavioral Therapy
Behavioral
therapy
Combined
therapy*
Pharmacologic Combined
therapy
therapy*
Mean reduction in UUI (%)
0
–10
–20
–30
–40
–50
–60
–57.5
–70
–72.7
–80
–90
–84.3
–88.5
–100
P = 0.034
N = 197
* Behavioral therapy and pharmacotherapy
P = 0.001
Burgio KL, et al. J Am Geriatr Soc. 2000;48:370-374.
Outcome Measures
1. Objective versus subjective measures
2. Metrics for urgency:
– Urgency severity
– Warning time
Correlation of
Subjective and Objective Measures
Patient-Reported
Outcomes (PROs)
• Meaningful improvements for
the patient
• Changes captured by PROs
may differ and include more
information than those
captured by bladder diaries
Tools
• Bladder diaries
• OAB-q:
– 8-item Symptom Bother scale
– 25-item HRQOL scale (concern,
sleep, social interaction, and
coping)
• PPBC:
– Single item of 6 statements
Coyne KS, et al. Int J Clin Pract. 2008;62:925-931.
Metrics for Urgency: Reduction in
Urgency Severity
Weeks
Reduction in urgency severity
score/void (IUSS) from baseline
1
4
12
0
–0.1
–0.2
P = 0.0002
–0.3
P = 0.0008
P = 0.0004
–0.4
Trospium 60 mg daily
(n = 292)
Placebo
(n = 300)
–0.5
Trospium significantly reduced urgency severity
episodes in patients with OAB
IUSS: Indevus Urgency Severity Scale
Staskin D, et al. J Urol. 2007;178(3 pt 1):978-983.
Antimuscarinics and Warning Time
in OAB: Impact of Urgency
Median change in warning
time from baseline (seconds)
First study to demonstrate
significant increase in warning time
in a large clinical setting (VENUS)
50
(n = 739; solifenacin vs placebo)1
31.5 *
– More time to reach a toilet
– Avoid urge incontinence
episodes
30
20
12.0
(n = 372)
(n = 367)
0
Solifenacin
(5-10 mg daily)
Placebo
* P = 0.032
Primary end point: mean reduction in
urgency episodes per 24 hours: 3.91 for
solifenacin vs 2.73 for placebo (P < 0.001)
1Toglia
2Zinner
– Time from first sensation of
urgency to voiding1-3
• Increase in warning time
significant to patients1-3:
40
10
• Warning time:
M, et al. Neurourol Urodyn. 2006;25:655. Abstract 123.
N, et al. Int J Clin Pract. 2006;60:119-126.
• Other warning time placebocontrolled studies:
– Darifenacin 15 mg daily
(P = not significant; N = 432)2
– Darifenacin 30 mg daily
(P = 0.003; N = 67)3
– Oxybutynin 2.5 mg TID
(P < 0.001; N = 44)4
3Cardozo
4Wang
L, et al. J Urol. 2005;173:1214-1218.
AC, et al. Urology. 2006;68:999-1004.
Optimizing Treatment Success: Using
Flexible-Dosing Options
OAB Patients Frequently
Request Dose Adjustments
Percent of patients requesting a dose increase at 4 weeks*1
48%
Solifenacin 10 mg
Solifenacin 5 mg (n = 578)
Higher dose (10 mg) available
51%
Tolterodine ER 4 mg + placebo
Tolterodine ER 4 mg (n = 599)
Start
Higher dose not available
4 weeks
12 weeks
• Similar results (59% vs 68%) were obtained after 2 weeks by a 12-week
efficacy, safety, and tolerability study of darifenacin vs placebo2
* Prospective 12-week, parallel-group, double-dummy,
2-arm, double-blind, efficacy and safety study
1Chapple
CR, et al. Eur Urol. 2005;48:464-470.
W, et al. BJU Int. 2005;95:580-586.
2Steers
Antimuscarinic Flexible Dosing (1)
Incontinent patients reporting no
incontinence episodes (%)
STAR Study: Incontinent Patients Reporting
No Incontinence Episodes at End Point on a 3-Day
Diary*
100
80
60
59 †
49
40
20
0
Baseline
(per 24 hours):
Solifenacin
Tolterodine ER
2.77 episodes
2.55 episodes
* Patients who reported experiencing incontinence episodes per 24 hours at
baseline and who did not report any episodes of incontinence for 3 consecutive
days prior to the study visit
†P
= 0.006 vs tolterodine ER
Chapple CR, et al. Eur Urol. 2005;48:464-470.
Antimuscarinic Flexible Dosing (2)
Flexible-Dosing Study
Reduction in incontinence episodes per week with darifenacin
No Dose Escalation
7.5 mg
Median change from
baseline (%)
0
7.5 mg
(n = 104)
Dose Escalation
7.5 mg
15 mg
(n = 157)
Placebo
0 mg
0 mg
(n = 127)
-20
-28.6
-40
-60
-35.7
-48.1
-49.2
-61.3
-80
-64.8
■ 2 weeks
■ 12 weeks
Steers W, et al. BJU Int. 2005;95:580-586.
Antimuscarinic Flexible Dosing (3)
Cumulative Response Rate With Increasing Dose
5 mg
10 mg
15 mg
20 mg
25 mg
30 mg
Percent of patients
100
80
60
40
20
0
≥ 70% decrease in urge episodes
N = 368
Complete dryness
MacDiarmid SA, et al. J Urol. 2005;174(4 pt 1):1301-1305.
Dosing Options Comparison
Antimuscarinic
Dosing
Dose Adjustment?
Darifenacin
7.5 and 15 mg
Oxybutynin
IR 5 mg
ER 5, 10, 15 mg
TDS 3.9 mg/day system
Daily
YES
BID, TID, QID
NO
Daily (up to 30 mg/day)
New patch twice a week
(every 3-4 days)
YES
Daily
YES
Daily
NO
BID
Daily
NO
NO
NO
Solifenacin
5 and 10 mg
Tolterodine ER
4 mg
Trospium chloride*
20 mg
60 mg
* 1 hour before meal or on an empty stomach
IR: immediate release
TDS: transdermal delivery system
Physicians’ Desk Reference. 62nd ed. Montvale, NJ: Thomson PDR; 2008.
Low Patient Persistence
Medicaid and Prescription Drug Databases
Patients remaining persistent (%)1
100
Only 44% out of 1637 Medicaid patients
remained persistent after 30 days
•
80
– Adherence rates reported for OAB
similar to other chronic diseases5
– Low level of education and cultural and
social support factors may contribute
to poor compliance6
Tolterodine ER
Oxybutynin ER
60
40
•
Antimuscarinic therapy for OAB3,5-6:
– Short- and long-term efficacy for
significant proportion of users
– Therapeutic/patient perceived benefits
require at least 4-8 weeks of
continuous therapy
20
60
90
12
0
15
0
18
0
21
0
24
0
27
0
30
0
33
0
36
0
0
0
30
Low adherence and persistence
reported by various clinical
studies2-4:
Days
Persistence: time to discontinuation
1Adapted
from Shaya FT, et al. Am J Manag Care. 2005;11(4 suppl):S121-S129.
MA, et al. Value Health. 2004;7:366. Abstract PUK11. 3Yu YF, et al. Value Health. 2005;8:495-505.
4Balkrishnan R, et al. J Urol. 2006;175(3 pt 1):1067-1071. 5Basra RK, et al. BJU Int. 2008. Epub ahead of print.
6Thomas L, et al. J Manag Care Pharm. 2008;14:381-386.
2Chui
Factors Affecting Adherence
• Presentation and efficacy of medication
• Cost (financial or personal)
• Dosing frequency
• Expectations of treatment
• Route of administration of medication
• Adequate follow-up after initiation of therapy
Follow-up is important to ensure patient adherence to treatment
Basra RK, et al. BJU Int. 2008. Epub ahead of print.
D’Souza AO, et al. J Manag Care Pharm. 2008;14:291-301.
OAB in Male Patients
Case Study 2: Tom
Presentation
• Tom, aged 60 years, presents to your office for his
annual physical examination
• At the end of the examination, he asks about the
definition of normal voiding:
– Works at night
– Frequent bathroom visits interrupt his work
– Slow urine stream and feeling that bladder has not emptied
completely
• Unremarkable medical history and physical
examination:
– Checked blood sugar levels
• Normal laboratory values
Differential Diagnosis of Symptoms
in Men With OAB
Men
Benign prostatic hyperplasia (BPH)
Prostate cancer
Diabetes
Postsurgical incontinence
Bladder outlet obstruction (BOO)
Urethral stricture
Neurogenic bladder
Bladder stones
Rosenberg MT, et al. Cleve Clin J Med. 2007;74(suppl 3):S21-S29.
Men With OAB: LUTS
Storage and Voiding Symptoms
Storage1,2
Voiding1,2
(afferent, irritative)
(efferent/obstructive)
Urgency
Hesitancy
Postvoid dribble
Frequency
Poor flow/weak stream
Nocturia
Intermittency
Sense of
incomplete emptying
UUI
Straining to pass urine
SUI
Terminal dribble
MUI
Prolonged micturition
Overflow incontinence
Urinary retention
Postmicturition1,2
1Abrams
P, et al. Neurourol Urodyn. 2002;21:167-178.
CR, et al. Eur Urol. 2006;49:651-658.
2Chapple
Clinical Algorithm for the
Management of LUTS in Men
Focused history and
physical examination
Urinalysis/PSA
Blood sugar
LUTS
Watchful
waiting
No
Ineffective
< 50 cc
PSA: prostate-specific antigen
PVR: postvoid residual
Referral
and/or treat
Desires treatment
Provisional OAB
Check PVR
Unlikely BPH or OAB
Provisional BPH
Trial α-blocker
50-200 cc
Effective
Continue
medication
> 200 cc
Referral
Rosenberg MT, et al. Int J Clin Pract. 2007;61:1535-1546.
Clinical Algorithm for the
Management of LUTS in Men (Cont.)
Check PVR
< 50 cc
Possible
OAB
50-200 cc
Diagnosis
unclear
Uroflow
High
Low
Optional
• Titrate α-blocker
• Switch medication
• Try ARI, combination therapy
• Refer
Mixed OAB/BPH
Antimuscarinics
Ineffective
Referral
> 200 cc
Referral
Effective
Continue
therapy
Ineffective
High
Uroflow
Low
Referral
Effective
Continue
medication
ARI: α-reductase inhibitor
Rosenberg MT, et al. Int J Clin Pract. 2007;61:1535-1546.
Low Risk of Retention in Men on
Antimuscarinics for OAB/LUTS
Evidence From Trials
Study/Goal
Result
Antimuscarinic
No clinically meaningful
monotherapy in men
change in PVR or urinary
with BOO/DO versus
retention
placebo
Reference(s)
Abrams P, et al. J Urol.
2006;175(3 pt 1):999-1004.
(Tolterodine ER)
Combined therapy:
α-blocker plus
antimuscarinics in
men
Increased benefit with
combination therapy
Low incidence of
retention
Varying results for PVR
increase
Kaplan SA, et al. JAMA.
2006;296:2319-2328.
Antimuscarinic
therapy in men with
OAB with or without
BPH medication
Low incidence of
retention, no
catheterization
Staskin DR, et al. Int J Clin
Pract. 2008;62:27-38.
* Not available in the United States
DO: detrusor overactivity
(Tolterodine ER plus tamsulosin)
Lee K-S, et al. J Urol.
2005;174(4 pt 1):1334-1338.
(Propiverine hydrochloride* plus
doxazosin ER)
(Oxybutynin TDS)
OAB Symptom Improvement in
Men: Patient-Reported Outcomes
Percent of
male respondents
■ PPBC = 1, 2, or 3
■ PPBC = 4, 5, or 6
•
100
80
60
Antimuscarinic treatment
effective and well tolerated
in men with OAB:
– Regardless of history of
“prostate condition”
40
20
0
Baseline
1
2
3
4
5
6
Global assessment of OAB
severity
Month
■ Always
■ Most of the time
■ Sometimes, infrequently, or never
Percent of
male respondents
100
“Within the past month, do
you feel that you had enough
time to get to the bathroom?”
80
60
40
20
0
Baseline
1
2
3
Month
N = 369 men with PPBC ≥ 4
(condition caused moderate,
severe, or many severe problems)
4
5
6
MATRIX: open-label study with oxybutynin TDS
Staskin DR, et al. Int J Clin Pract. 2008;62:27-38.
Case Study 2: Tom
Treatment and Follow-Up
• You use a questionnaire to assess Tom’s symptoms
• Behavioral modifications
• You start him on an α-blocker:
– At follow-up, obstruction has improved
• He still complains of nocturia and you add
antimuscarinic treatment:
– After 4 weeks of antimuscarinic treatment, his nocturia episodes
have been reduced to 2 times a night
Summary
• OAB is a prevalent disease that increases with age
• OAB impacts comorbidities and QOL
• OAB symptoms can be treated:
– Move toward symptom/syndrome-based treatment
– Individualized to match patient’s preference and expectations
(tolerability and efficacy)
– Recognize comorbidities and treatment fluid imbalances
– Institute behavioral changes and pelvic floor exercises
– Flexible-dosing regimens
Postmeeting Survey
•
True or false: The core symptom of OAB is
urgency.
1. True
2. False
?
Postmeeting Survey
•
Which of the following are NOT considered
comorbidities in patients with OAB?
1.
2.
3.
4.
Falls and fractures
UTIs
Skin infections
Kidney stones
?
Postmeeting Survey
•
True or False: Using a flexible-dosing regimen of
antimuscarinics results in improved efficacy and
patient satisfaction.
1. True
2. False
?
Generic/Brand Name Table
Generic
Trade
Darifenacin
Enablex®
Doxazosin
Cardura ®
Fluoxetine
Prozac®, Sarafem®
Ketoconazole
Extina®, Nizoral®, Xolegel®
Oxybutynin
Ditropan®, Oxytrol®
Paroxetine
Paxil®, Pexeva®
Propiverine
Not available in the United States
Solifenacin
VESIcare®
Tolterodine
Detrol®
Trospium
Sanctura XR™