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. True2. False
?
Premeeting Survey
• Which of the following are NOT considered comorbidities in patients with OAB?
1. Falls and fractures2. Urinary tract infections (UTIs)3. Skin infections4. Kidney stones
?
Premeeting Survey
• True or False: Using a flexible-dosing regimen of antimuscarinics results in improved efficacy and patient satisfaction.1. True2. 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 P, et al. Neurourol Urodyn. 2002;21:167-178.2 Wein AJ, et al. Urology. 2002;60(5 suppl 1):7-12.ICS: International Continence Society
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 dayNormal is < 8 times per 24 hours
Nocturia1,2 Waking to urinate during sleep hoursConsidered 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;21:167-178.2Wein AJ, et al. J Urol. 2006;175(3 pt 2):S5-S10.
3Zinner N, et al. Int J Clin Pract. 2006;60:119-126.
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.
Population-based prevalence studies::Comparison of data from the SIFO study (1997)*1
and the EPIC study (2005)†2
1Milsom I, et al. BJU Int. 2001;87:760-766.2Irwin DE, et al. Eur Urol. 2006;50:1306-1314.
Pre
vale
nce
(%
)
0
5
10
15
20
25
30
35
40
Age (years)
18-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 > 70
Men (SIFO 1997)
Men (EPIC 2005)Women (SIFO 1997)
Women (EPIC 2005)
16.6
11.8
SIFO: Sifo/Gallup telephone survey* N = 16,776 interviews (6 European countries)† N = 19,165 interviews (4 European countries and Canada)
OAB Symptoms Are as Prevalent in Men as in Women and Increase
With Age
Urgency Leading to Urgency Incontinence: More Prevalent in
Women
With UUI55%
With UUI16%
Without UUI45%
Without UUI84%
Women with OAB(n = 463)
Men with OAB(n = 401)
National Overactive Bladder Evaluation StudyStewart 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
• 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.
Patients Would Rather Cope With OAB Than Seek
Help Due to:
OAB Symptoms Negatively Affect Patients
59.3
47.3 49.2
38.132.5 33.5
30.3 31.3
7.2
16.7 14.820.5
1.0 2.45.6
10.1
0
20
40
60
80
100
Frequency Nocturia Urgency UUI
A lot Moderately A little Omitted or not applicable
Sand P, et al. BJU Int. 2007;99:836-844.
Per
cen
t o
f p
atie
nts
HRQOL assessed with King’s Health QuestionnaireN = 2878
Women Prefer Clinicians to Initiate Discussion About Urinary
Symptoms
37 35 33
43
0
10
20
30
40
50
Total SUI UUI MUI
• Participant question: “I would be more comfortable discussing urinary symptoms if my health care provider brought up the topic.”
Per
cen
tag
e o
f w
om
en(a
gre
e st
ron
gly
or
com
ple
tely
)
MacDiarmid S, et al. Curr Med Res Opin. 2005;21;1413-1421.
SUI: stress urinary incontinenceMUI: mixed urinary incontinence
(n = 1046)(n = 1046) (n = 386)(n = 386) (n = 271)(n = 271) (n = 389)(n = 389)
4.7 3.9
10.5
28.025.3
1.8 2.34.9
8.4
16.1
0
5
10
15
20
25
30
Vulvovaginitis Skin infections Depression UTIs Falls andfractures
Per
cen
tag
e o
f p
atie
nts
OAB Control
Look for Comorbidities of OAB
• 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
Adapted from Darkow T, et al. Pharmacotherapy. 2005;25:511-519.11,556 adult patients with OAB and 11,556 controls matched on propensity score
P < 0.0001
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 Do You Approach a
Conversation About Urinary Problems Like OAB?
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):37-40.2Rosenberg MT, et al. Cleve Clin J Med. 2005;72:149-156.
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: CarolPresentation
• 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;13:154-158.2Newman 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.
• 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=10931&nbr=005711&string=incontinence
• Strength of evidence: – Level A– Can be recommended as a noninvasive treatment in many
women
Clinical Practice Recommendation
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: CarolTreatment
• 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
WomenUTI
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 Incontinencein Women
Adapted from Kirby M, et al. Int J Clin Pract. 2006;60:1263-1271.ICI: International Consultation on Incontinence
Incontinence on physical
activity
Incontinence with mixed symptoms
Incontinencewith
urgency/frequency
MUISUI UUI
Antimuscarinics
Treat most bothersome
symptoms for MUI
Pelvic floor muscle trainingBladder retraining
Evaluation
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:• Environment• Expectations• Lifestyle• Age• Health
1Robinson D, et al. Int Urogynecol J Pelvic Floor Dysfunct. 2007;18:273-279.2Cardozo L. BJU Int. 2007;99(suppl 3):1-7.
Not tailoring treatment may lead to2:• Disillusionment• Avoidable adverse events• Unneeded use of time and resources• Harmful and unnecessary surgery• Morbidity/mortality• Worsening symptoms
• 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
Clinical Practice Recommendation
Symptom-Based OAB Management
58.0 48.3 48.6 49.7 50.4
28.329.7 29.9 24.9 28.4
0
20
40
60
80
100
Urgency Frequency(day)
Nocturia UUI Total
Pe
rce
nt
of
pa
tie
nts
Major improvement Minor improvement
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
1Roberts R, et al. Int J Clin Pract. 2006;60:752-758.2Elinoff V, et al. Int J Clin Pract. 2006;60:745-751.
* IMPACT: tolterodine extended release (ER) 12-week, open-label study
Patient perception of improvement in overall bladder condition at week 12*1
Questionnaires used:OAB symptom questionnaire
(OAB-q)American Urological Association
Symptom IndexPatient Perception of Bladder
Condition (PPBC)
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.
1Steers WD. Urol Clin North Am. 2006;33:475-482.2Erdem N, et al. Am J Med. 2006;119(3 suppl 1):29-36.
3Staskin DR. Drugs Aging. 2005;22:1013-1028.4Physicians’ Desk Reference. 62nd ed. Montvale, NJ: Thomson PDR; 2008.
5Swart PJ, et al. Basic Clin Pharmacol Toxicol. 2006;99:33-36.
* eg, paroxetine (SSRI) shares CYP2D6 liver metabolism with darifenacin† eg, ketoconazole, fluoxetine (SSRI) SSRI: selective serotonin reuptake inhibitor
Potential Adverse Events, Contraindications, and Drug
Interactions of Antimuscarinics
Most common side effectsDry 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
ContraindicationsUrinary or gastric retention4
Uncontrolled narrow-angle glaucoma4
Drug interactions
Antidepressants*2,3
Polypharmacy in the elderly2
CYP3A4 inhibitors†3,5
Diuretic effect of alcohol2
Adverse Events Decline Over Time*
0
10
20
30
40
50
0 to 3 > 3 to 6 > 6 to 9 > 9 to 12 > 12 to15
> 15 to18
> 18 to21
> 21 to24
> 24
Dry mouth Constipation
Haab F, et al. BJU Int. 2006;98:1025-1032.
Consistent finding across long-term studies for OAB:adverse events are most common within 3 months of therapy
and decline thereafter
Per
cen
t o
f p
atie
nts
Treatment duration (months)
N = 716* 24-month, noncomparative, darifenacin, open-label extension study
Burgio KL, et al. J Am Geriatr Soc. 2000;48:370-374.
N = 197* Behavioral therapy and pharmacotherapy
Enhanced Therapeutic Effects With Combined Pharmacologic
and Behavioral Therapy
P = 0.034P = 0.001
Behavioral therapy
Combined therapy*
Pharmacologic therapy
Combined therapy*
–57.5
–88.5
–72.7
–84.3
–100
–90
–80
–70
–60
–50
–40
–30
–20
–10
0
Mea
n r
edu
ctio
n i
n U
UI
(%)
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) Tools
• Meaningful improvements for the patient
• Changes captured by PROs may differ and include more information than those captured by bladder diaries
• 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.
Staskin D, et al. J Urol. 2007;178(3 pt 1):978-983.
Red
uct
ion
in
urg
ency
sev
erit
y sc
ore
/vo
id (
IUS
S)
fro
m b
asel
ine
Metrics for Urgency: Reduction in Urgency Severity
IUSS: Indevus Urgency Severity Scale
Weeks
P = 0.0002
P = 0.0008
P = 0.0004
(n = 292) (n = 300)–0.5
–0.4
–0.3
–0.2
–0.1
01 4 12
Trospium 60 mg daily Placebo
Trospium significantly reduced urgency severity episodes in patients with OAB
• Warning time:– Time from first sensation of
urgency to voiding1-3
• Increase in warning time significant to patients1-3:– More time to reach a toilet– Avoid urge incontinence
episodes
• Other warning time placebo-controlled 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
31.5
12.0
0
10
20
30
40
50
Solifenacin Placebo
Med
ian
ch
ang
e in
war
nin
g
tim
e fr
om
bas
elin
e (s
eco
nd
s)
(5-10 mg daily)
(n = 372) (n = 367)
First study to demonstrate significant increase in warning time in a large clinical setting (VENUS)
(n = 739; solifenacin vs placebo)1
*
1Toglia M, et al. Neurourol Urodyn. 2006;25:655. Abstract 123. 2Zinner N, et al. Int J Clin Pract. 2006;60:119-126.
* P = 0.032Primary end point: mean reduction in urgency episodes per 24 hours: 3.91 for solifenacin vs 2.73 for placebo (P < 0.001)
3Cardozo L, et al. J Urol. 2005;173:1214-1218. 4Wang AC, et al. Urology. 2006;68:999-1004.
Antimuscarinics and Warning Time in OAB: Impact of Urgency
Optimizing Treatment Success: Using Flexible-Dosing Options
OAB Patients Frequently Request Dose Adjustments
1Chapple CR, et al. Eur Urol. 2005;48:464-470.2Steers W, et al. BJU Int. 2005;95:580-586.
* Prospective 12-week, parallel-group, double-dummy, 2-arm, double-blind, efficacy and safety study
Percent of patients requesting a dose increase at 4 weeks*1
51%Tolterodine ER 4 mg + placeboTolterodine ER 4 mg + placebo
Tolterodine ER 4 mg (n = 599) Tolterodine ER 4 mg (n = 599) Higher dose not available
48%
Solifenacin 5 mg (n = 578)Solifenacin 5 mg (n = 578)
Solifenacin 10 mgSolifenacin 10 mg
Higher dose (10 mg) available
Start 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
Inco
nti
nen
t p
atie
nts
rep
ort
ing
no
in
con
tin
ence
ep
iso
des
(%
)
5949
0
20
40
60
80
100
Solifenacin Tolterodine ER
†
Chapple CR, et al. Eur Urol. 2005;48:464-470.† P = 0.006 vs tolterodine ER
Antimuscarinic Flexible Dosing (1)STAR Study: Incontinent Patients Reporting
No Incontinence Episodes at End Point on a 3-Day Diary*
Baseline (per 24 hours):
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
-28.6
-64.8
-48.1
-35.7
-49.2
-61.3
-80
-60
-40
-20
0
7.5 mg 15 mg
Dose Escalation
7.5 mg 7.5 mg
No Dose Escalation
Med
ian
ch
ang
e fr
om
b
asel
ine
(%)
(n = 104) (n = 157)
Reduction in incontinence episodes per week with darifenacin
Steers W, et al. BJU Int. 2005;95:580-586.
0 mg 0 mg
Placebo
(n = 127)
Antimuscarinic Flexible Dosing (2)Flexible-Dosing Study
■ 2 weeks■ 12 weeks
0
20
40
60
80
100
≥ 70% decrease in urge episodes Complete dryness
5 mg 10 mg 15 mg 20 mg 25 mg 30 mg
MacDiarmid SA, et al. J Urol. 2005;174(4 pt 1):1301-1305.
Per
cen
t o
f p
atie
nts
N = 368
Antimuscarinic Flexible Dosing (3)Cumulative Response Rate With Increasing Dose
Dosing Options Comparison
Antimuscarinic Dosing Dose Adjustment?
Darifenacin 7.5 and 15 mg Daily YES
Oxybutynin IR 5 mg BID, TID, QID NO
ER 5, 10, 15 mg Daily (up to 30 mg/day) YES
TDS 3.9 mg/day systemNew patch twice a week (every 3-4 days)
NO
Solifenacin 5 and 10 mg Daily YES
Tolterodine ER 4 mg Daily NO
Trospium chloride* 20 mg 60 mg
BIDDaily
NONO
Physicians’ Desk Reference. 62nd ed. Montvale, NJ: Thomson PDR; 2008.
* 1 hour before meal or on an empty stomachIR: immediate releaseTDS: transdermal delivery system
0
20
40
60
80
100
Tolterodine EROxybutynin ER
Days
Pat
ien
ts r
emai
nin
g p
ers
iste
nt
(%)1 • Low adherence and persistence
reported by various clinical studies2-4:
– 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
• 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
Low Patient Persistence Medicaid and Prescription Drug Databases
Persistence: time to discontinuation1Adapted from Shaya FT, et al. Am J Manag Care. 2005;11(4 suppl):S121-S129.
2Chui 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.
Only 44% out of 1637 Medicaid patients remained persistent after 30 days
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
Basra RK, et al. BJU Int. 2008. Epub ahead of print.D’Souza AO, et al. J Manag Care Pharm. 2008;14:291-301.
Follow-up is important to ensure patient adherence to treatment
OAB in Male Patients
Case Study 2: TomPresentation
• 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
MenBenign 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: LUTSStorage and Voiding Symptoms
Storage1,2
(afferent, irritative)Voiding1,2
(efferent/obstructive)Postmicturition1,2
Urgency
Frequency
Nocturia
UUI
SUI
MUI
Overflow incontinence
Hesitancy
Poor flow/weak stream
Intermittency
Straining to pass urine
Terminal dribble
Prolonged micturition
Urinary retention
Postvoid dribble
Sense of incomplete emptying
1Abrams P, et al. Neurourol Urodyn. 2002;21:167-178.2Chapple CR, et al. Eur Urol. 2006;49:651-658.
Clinical Algorithm for the Management of LUTS in Men
LUTS
Focused history and physical examination
Urinalysis/PSABlood sugar
Desires treatment
Trial α-blocker Continuemedication
Watchfulwaiting
EffectiveIneffective
Provisional OAB Provisional BPH
< 50 cc 50-200 cc > 200 cc Referral
Check PVR
No
Referraland/or treat
Unlikely BPH or OAB
Rosenberg MT, et al. Int J Clin Pract. 2007;61:1535-1546.PSA: prostate-specific antigenPVR: postvoid residual
Clinical Algorithm for the Management of LUTS in Men (Cont.)
Optional• Titrate α-blocker• Switch medication• Try ARI, combination therapy• Refer
Uroflow
UroflowHigh Low
High Low
Antimuscarinics
< 50 cc 50-200 cc > 200 cc Referral
Continuetherapy
Referral
ReferralContinue
medication
Effective
Ineffective
IneffectiveEffective
PossibleOAB
Mixed OAB/BPH
Diagnosisunclear
Check PVR
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 Reference(s)
Antimuscarinic monotherapy in men with BOO/DO versus placebo
No clinically meaningful change in PVR or urinary retention
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 therapyLow incidence of retentionVarying results for PVR increase
Kaplan SA, et al. JAMA. 2006;296:2319-2328. (Tolterodine ER plus tamsulosin)
Lee K-S, et al. J Urol. 2005;174(4 pt 1):1334-1338. (Propiverine hydrochloride* plus doxazosin ER)
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. (Oxybutynin TDS)
* Not available in the United StatesDO: detrusor overactivity
“Within the past month, do you feel that you had enough time to get to the bathroom?”
Global assessment of OAB severity
OAB Symptom Improvement in Men: Patient-Reported Outcomes
• Antimuscarinic treatment effective and well tolerated in men with OAB:
– Regardless of history of “prostate condition”
Staskin DR, et al. Int J Clin Pract. 2008;62:27-38.
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N = 369 men with PPBC ≥ 4 (condition caused moderate, severe, or many severe problems)
■ PPBC = 1, 2, or 3 ■ PPBC = 4, 5, or 6
■ Always ■ Most of the time■ Sometimes, infrequently, or never
MATRIX: open-label study with oxybutynin TDS
Case Study 2: TomTreatment 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. True2. False
?
Postmeeting Survey
• Which of the following are NOT considered comorbidities in patients with OAB?
1. Falls and fractures2. UTIs3. Skin infections4. Kidney stones
?
Postmeeting Survey
• True or False: Using a flexible-dosing regimen of antimuscarinics results in improved efficacy and patient satisfaction.1. True2. 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™