2. Today’s outline
o OAB syndrome introduction (definition and risk factor)
o OAB treatment guideline and medical choice
o BPH with OAB medical treatment
o Frequency and Nocturia
20200702高雄市醫師公會
3. Today’s outline
o OAB syndrome introduction (definition and risk factor)
o OAB treatment guideline and medical choice
o BPH with OAB medical treatment
o Frequency and Nocturia
20200702高雄市醫師公會
4. What is OAB
o Key symptom : Urgency
o Sudden and compelling desire to pass urine that is difficult to defer
o OAB is a syndrome
o Idiopathic
o Sensory dysfunction
o Urothelial dysfunction
o Myogenic dysfunction
o Neurogenic dysfunction
o May related to bladder outlet obstruction or neurogenic
急尿
突然會有一種很強烈的慾望想去排尿
20200702高雄市醫師公會
5. Detrusor Overactivity and OAB
OAB, overactive bladder; UUI, urge urinary incontinence.
1. Abrams P et al. The Overactive Bladder: A Widespread and Treatable Condition. Stockholm, Sweden: Erik Sparre Medical; 1998.
2. Ouslander J. N Engl J Med. 2004;350(8):786-799.
Bladder
pressure
Bladder filling
Filling phase
Bladder filling
Emptying
phase
Involuntary bladder contraction
Filling phase
OAB wet/ Urge incontinence
20200702高雄市醫師公會
7. Etiology of LUTS
o Urologic disease
o BPH with obstruction
o Pelvic organ prolapse with
obstruction
o Detrusor weakness and/or
instability
o UTI
o Chronic or acute prostatitis
o Urinary stone
o Malignancy : prostate or
bladder
o Interstitial cystitis / Bladder
pain syndrome
o Non-urologic disease
o Neurological disease (multiple
sclerosis, spinal cord injury,
cauda equina syndrome ,
Parkinsonism, stroke,
dementia)
o Medical disease
o DM
o HTN
o CHF
o COPD
o Autoimmune disease
o (SLE, Sjögren,RA)
o CKD
o Liver cirrhosis
o Medication related
8. OAB is a prevalent condition that
increases with age
1. Milsom I, et al. BJU Int 2001;87:760–6; 2. Stewart WF, et al. World J Urol 2003;20:327–36.
US NOBLE Study2
Stewart WF, et al. 2003
EU Study1
Milsom I, et al. 2001
OAB, overactive bladder; EU, European; US, United states; NOBLE, National Overactive
Bladder Evaluation.
Age (years)
Prevalence(%)
10
15
20
25
30
35
40
45
40–44 45–49 50–54 55–59 60–64 65–69 70–74 75+
Men
Women
5
0
Age (years)
Prevalence(%)
25–3418–24 35–44 45–54 55–64 65–74 75+
Men
Women
10
15
20
25
30
35
40
5
0
Increasedprevalence
8
9. 0
5
10
15
20
25
30
35
40
30-39 40-49 50-59 60-69 70-79 Overall Adjusted
All Participants
Men
Women
OAB的盛行率
HJ Yu. Urol Int. 2006;77(4):327-33
* Adjusted: The prevalence is adjusted to the whole registered population
由內政部人口統計推算，約有1.2百萬人
10. Today’s outline
o OAB syndrome introduction (definition and risk factor)
o OAB treatment guideline and medical choice
o BPH with OAB medical treatment
o Frequency and Nocturia
20200702高雄市醫師公會
19. o Vesicare®長期治療 (52週)各項症狀能持續的改善
Haab F et al. European Urology 47 (2005) 376-384
Vesicare® (Solifenacin)
長期療效試驗
Median percent reductions in frequency, urgency, and nocturia based on solifenacin exposure over time
URO-TW-2017021
24. Nerve pathways in
normal bladder control
Mode of action of
OAB treatments
1. Neurourology and Urodynamics 2007, 26:752–756.
2. Adapted from Chu FM, Dmochowski R. Am J Med 2006;119(3 Suppl 1):3–8.
32. o Neurotoxin derived from the anaerobic bacterium clostridium botulinum
o Ach release blockage: pre-synaptic effect Chemodenervation
o 2000 Shurch and Stohrer Botulinum-A toxin for treatment detrusor hyperreflexia in spinal cord
injured patients
o 2011 approved by FDA for treatment of NDO
o 2013 approved by FDA for treatment of idiopathic DO who are intolerant or refractory to
antimuscarnics
o alleviate symptoms of urinary incontinence
o refractory to anti-cholinergic therapy and/or behavioral therapy
Botulinum Toxin (BTX)
35. Today’s outline
o OAB syndrome introduction (definition and risk factor)
o OAB treatment guideline and medical choice
o BPH with OAB medical treatment
o Frequency and Nocturia
20200702高雄市醫師公會
36. OAB BPH
LUTS
Overlap of storage and voiding
LUTS in OAB and BPH
Only 25-50% of men with BPH have LUTS
Only 48-53% of male LUTS was urodynamically
confirmed to have BOO (bladder outlet
obstruction)
Eckhardt MD, et al. Urology. 2001 Dec;58(6):966-71.
Focus has shifted from
prostate to bladder
recently
39. Rationale of using antimuscarinics +α-
blocker in BPH with OAB
o For pathophysiology
▲ Most common cause of OAB is detrusor overactivity
(DO)
Afferent signal noise generated by local Ach release
▲ BOO could cause denervation hypersensitivity of
cholinergic receptor
40. Level 1b study
Reference No.
pt
Treatment Follow-
up wk
Type of study Level
Lee et al 142 Propiverine
Doxazosin
8 prospective .RCT
double –blind
1b
Kaplan et al 225 Tolterodine
tamsulosin
12 prospective .
RCT
double-blind
1b
MacDiarmid et
al
203 Oxybutinin
tamsuloin
12 prospective,
randomized ,
placebo-
controlled
double-blind
1 b
Chapple et al 283 Tolterodine
ER
α-blocker
12 prospective,
placebo-
controlled
double-blind
1b
Kaplan et al 398 Solifenacin
tamsulosin
12 prospective,
placebo-
controlled
double-blind
1b
41. Level 1b study
Reference No. pt
(2
drug)
Treatment Follow-
up wk
Type of study Level
Kaplan et al 251 fesoterodine
α-blocker
12 prospective
randomized
double-blind
1b
Yamaguchi et
al
198+
196
solifenasin
tamsulosin
12 prospective,
randomized ,
placebo-
controlled
double-blind
1 b
42. Change of frequency from baseline
Chapple CR et al. Eur Urol. 2009;56:534-43; Kaplan SA et al. J Urol. 2009;182:2825-2830;
Yamaguchi O et al. Urology. 2011;78:126-33; Kaplan SA et al. BJU Int. 2012;109:1831-1840.
Kaplan et al. JAMA 2006
-1.7
-1.2
-0.67
-0.22
-1.5
-2.5
-1.8
-1.05
-1.27
-1.9
-3
-2.5
-2
-1.5
-1
-0.5
0
Kaplan 2006 Chapple
2009
Kaplan 2009 Yamaguchi
2011
Kaplan 2012
α blocker α blocker+ anticholinergic
P<0.001 p< 0.01 p-=0.135 p<0.001*
p<0.01 * vs. placebo
43. Change of urgency from baseline
-2.2
-1.8
-1.1
-1.93
-2.9
-3.2
-2.7
-2.18 -2.18
-3.2
Kaplan 2006 Chapple 2009 Kaplan 2009 Yamaguchi
2011
Kaplan 2012
α blocker α blocker+ anticholinergic
Chapple CR et al. Eur Urol. 2009;56:534-43; Kaplan SA et al. J Urol. 2009;182:2825-2830;
Yamaguchi O et al. Urology. 2011;78:126-33; Kaplan SA et al. BJU Int. 2012;109:1831-1840.
Kaplan et al. JAMA 2006
P<0.05 p< 0.001 p < 0.001 p=0.049*
p=0.196
* vs. placebo
44. Change of urge incontinence
-0.7
-0.8
-0.94
-0.85 -0.9
-1.08
Kaplan 2006 Chapple 2009 Yamaguchi 2011
α blocker α blocker+ anticholinergic
Kaplan et al. JAMA 2006
Chapple CR et al. Eur Urol. 2009;56:534-43
Yamaguchi O et al. Urology. 2011;78:126-33;
P<0.001 p > 0.05 P=0.351
45. Improves persistent storage symptoms
MacDiarmid SA et al. Mayo Clin Proc. 2008;83:1002-1010;
Chapple CR et al. Eur Urol. 2009;56:534-43; Kaplan SA et al. J Urol. 2009;182:2825-2830;
Yamaguchi O et al. Urology. 2011;78:126-33; Kaplan SA et al. BJU Int. 2012;109:1831-1840.
-2.4
-2.1
-2.4
-1.8
-2.1
-3.7
-2.6
-3.15
-2.4 -2.4
-4
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
MacDiarmid
2008
Chapple
2009
Kaplan
2009
Yamaguchi
2011
Kaplan
2012
MeanchangeinstorageIPSS
frombaseline
α1-AR antagonist + placebo α1-AR antagonist + antimuscarinic agent
P-value vs.
placebo
P<0.001
P=0.037
P<0.006
P=0.011 P>0.05
46. Change in PFR and PVR
MacDiarmid et al. Maya Clin Proc 2008;83:1002-10
Chapple et al Eur Urol 2009:56:34-43
47. Risk of AUR
Reference No. pt
(2 drug)
Treatment Follow-up
wk
No. of AUR
Lee et al 2005 142 Propiverine
Doxazosin
8 0
Kaplan et al 2006 225 Tolterodine
tamsulosin
12 2
MacDiarmid et al 203 Oxybutinin
tamsuloin
12 0
Chapple et al
2009
283 Tolterodine ER
α-blocker
12 3
Kaplan et al 2009 398 Solifenacin
tamsulosin
12 7
Kaplan et al 2012 251 fesoterodine
α-blocker
12 1
Yamaguchi et al 198+
196
solifenasin
tamsulosin
12 4
57. TAKE HOME MESSAGE
o OAB is a common aging disease , it may relate to BPH, neurogenic disease
or medical disease
o Lifestyle modification with medical therapy is the mainstay therapy
o Antimuscarinics and Beta3 agonist are effective and may be combined of
OAB pts
o Solifenacin has higher bladder selectivity and persistence rate than other
AM
20200702高雄市醫師公會
