Managingoveractivebladderinprimarycare

TAOngUrology

Acknowledgement

Onedayinyourclinic….•  60-year-oldman

•  Leakofurinewhencoughandsneeze….

Whattypeofincontinence?•  A.Coughincontinence•  B.Pressureincontinence•  C.Urgeincontinence•  D.Stressincontinence

Whattypeofincontinence?•  A.Coughincontinence•  B.Pressureincontinence•  C.Urgeincontinence• D.Stressincontinence(SUI)

•  StressUI(SUI)=involuntaryleakageoneffortorexertionoranysuddenincreaseinabdominalpressure.

Canthishappentoamale?

Nextdayinyourclinic….•  65-year-oldman

•  Urinaryfrequencyandurgency.

•  Occasionalleak…..

Whattypeofincontinence?•  A.Stressincontinence•  B.Overactiveincontinence•  C.Urgeincontinence•  D.Sensitiveincontinence

Whattypeofincontinence?•  A.Stressincontinence•  B.Overactiveincontinence•  C.Urgeincontinence(UUI)•  D.Sensitiveincontinence

•  UrgeUI(UUI)=involuntarylossofurineaccompaniedbyorimmediatelyprecededbyasudden,strongdesiretovoid(urgency).

Canthishappentoafemale?

OveractiveBladder•  OABdry

•  OABwet

DefinitionofOAB•  SAMEin2018.(asin2002;ICS)

•  Urinaryurgency,withorwithouturgencyincontinence,usuallyaccompaniedbyfrequencyandnocturia.

WhatifhavingbothstressPLUSurgeincontinence

•  A.Combinedincontinence•  B.Mixedincontinence•  C.Confusedincontinence•  D.Rojakincontinence

WhatifhavingbothstressPLUSurgeincontinence

•  A.Combinedincontinence

• B.Mixedincontinence•  C.Confusedincontinence•  D.Rojakincontinence

•  Mixedurinaryincontinence=symptomcomplexofinvoluntaryleakageassociatedwithbothurgencyandeffortandexertion.

FAQ•  Whichonetotreatfirst?

Also…•  Overflowincontinence

•  Functionalincontinence

Howtoevaluate?The3steps….•  History(identifytheproblem:OAB,LUTS,SUI,UUI,overflowetc;andtheCAUSE)

•  Examination

•  Investigation

Howtoevaluate?The3steps….•  History

•  Examination

•  Investigation

•  DRE•  Abdomen•  Genitalia:Meatalstenosis,phimosis•  Focusedneuroexam

Question•  WhatistheMUST-DOinvestigationsforpatientswithLUTS/incontinence/OAB?

Investigations•  ImportanttoruleoutUTIorsomethingsinister!

•  Urinalysis

•  +/-Renalfunctiontest•  +/-PSA•  +/-Imaging•  +/-uroflow•  +/-postvoidresidualurine•  +/-cystoscopy•  +/-urodynamics

Onelowcost,simple,oftenforgottenbutPOWERFULtool…..

Bladderdiary/voidingdiary

Urodynamics•  Forinfoonly.

•  Pdet+Pabd=Pves

•  Pdet=Pves-Pabd

IsUrodynamicsaMUST?

TreatmentofOAB/UrgeUI•  WhatistheFIRSTlinetherapy?•  A.Conservativemanagement•  B.Medicaltherapy•  C.Surgicaltherapy•  D.Notstandardtherapy

TreatmentofOAB/UrgeUI

TreatmentofUrgeUI

New:Fesoterodine

Sideeffects•  Drymouth•  Dryeye•  Constipation

– n/b:NOTtobeusedincaseofGLAUCOMA•  MUST–BE-ASKEDQUESTION!

Secondlinetherapy

•  Anticholinergics– Extendedrelease– Transdermalpatch

Metaanalysis•  Meta-analysisof50RCTs

•  >27,000subjectswithOAB

•  UI:Reducedby1.73episodes/day(placebo:1.06)

•  Noofvoid:Reducedby2.06/day(placebo:1.2)

•  Nosingleagentissuperiortoothers

Arethesideeffectsdifferent?

Arethesideeffectsdifferent?•  Drymouth,constipation…..Cognitiveimpairment…

•  Evidence??

Arethesideeffectsdifferent?•  Drymouth,constipation…..Cognitiveimpairment…

•  Verylittlehighqualityevidence.

•  Exceptoxybutynin.KesslerTM,BachmannLM,MinderC,etal.Adverseeventassessmentofantimuscarinicsfortreatingoveractivebladder:anetworkmetaanalyticapproach.PloSOne2011;6:e16718.

Howmanypatientsarestillonthedrugafter12months?

•  A.100%

•  B.>50%

•  C.<50%

Howmanypatientsarestillonthedrugafter12months?

• 14-35%

WaggA,CompionG,FaheyA,SiddiquiE.Persistencewithprescribedantimuscarinictherapyforoveractivebladder:aUKexperience.BJUInt2012;110:1767–74.

FAQ:Durationoftreatment•  Controversial.

•  Antimuscarinictolterodine(extended-release,4mg)inknownresponders,65%ofpatientsrequestedretreatmentand62%experiencedsymptomrelapse.

Newclassofdrug•  Beta3-agonist:Mirabegon

B3adrenoceptoragonist•  Mirabegon-firstagent,approvedbyFDAin2012.

•  Indications:– Upfront– Afterfailureofanticholinergics– Whenanticholinergicsarecontraindicated–  Incombinationwithanticholinergics

Noofmicturition/24hour

Noofincontinence/24hour

Adverse events n (%) Placebo (n=494) Mirabegron 50mg (n=493) Tolterodine ER 4mg (n=495)

Hypertension 38 (7.7 %) 29 (5.9%) 40 (8.1%)

Nasopharyngitis 8 (1.6%) 14 (2.8%) 14 (2.8%)

Dry Mouth 13 (2.6) 14 (2.8) 50 (10.1)

Headache 14 (2.8%) 18 (3.7%) 18 (3.6%)

Influenza 8 (1.6%) 11 (2.2%) 7 (1.4%)

Urinary tract infection 7 (1.4%) 7 (1.4%) 10 (2.0%)

Constipation 7 (1.4) 8 (1.6) 10 (2.0)

Data are for the safety analysis set. Adverse events, defined according to the Medical Dictionary for the Regulatory Activities (MedDRA version 9.1)

Study046-Commontreatment-emergentadverseevents(≥2%inanytreatmentgroup)

AdaptedfromKhullarV,etal.EurUrol2013;63:283–95

Dry Mouth 13 (2.6%) 14 (2.8%) 50 (10.1%)

Constipation 7 (1.4%) 8 (1.6%) 10 (2.0%)

51

Combination:Mirabegron+anticholinergic(EurUrol2015)

Combination:Mirabegron+anticholinergic(EurUrol2015)

SYMPHONY:Combinationbetter

Mirabegronafteranticholinergicfailure:EurUrol2016

Mirabegronafteranticholinergicfailure:EurUrol2016

BESIDE:Addingmirabegronhelps!

2018

Summary:Combo>Mono;welltolerated

Meta-analysis

Summary:Mirabegron-lessSEEfficacyofcombinationTx

InrefractoryOAB…•  Sacralneuromodulationorperipheraltibialnervestimulation(PTNS)

•  IntradetrusorinjectionofonabotulinumtoxinA

•  Bladderaugmentation

Botox•  SystemicReview

•  1,380patients

•  Reductioninnoofmicturition/24hr–29%

•  Reductioninnoofincontinence–59%

MangeraAetal.EurUrol2014;65:981–90.

Newerformulation&workinprogress

•  Dysport(abobotulinumtoxinA)

•  Methodofdelivery:electromotivedrugadministrationandliposomeinstillation

Newdrugsonthehorizon…•  NextB3-agonists(XX-begron…)

•  Neurokininreceptorantagonists•  Alpha-adrenoceptorantagonists•  Nervegrowthfactorinhibitors•  Genetherapy•  Stemcell–basedtherapies

Summary•  Theproblemisthere

•  Todiagnose

•  Tostartwithconservativemeasures,thenmedications.

•  Medications:Anticholinergics,B3agonist.

•  Specializedcentresfor3rdlinetherapy