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™