Page 13 - CUA guideline on adult overactive bladder

Corcos et al.

complete.assessment.across.different.drugs.by.Buser.et.al. Efficacy
performed.an.efficacy.and.adverse.events.analysis,.along.
with.a.trade-off.analysis.between.these.two.components..The. A.meta-analysis.of.four.phase.3.RCTs.found.that.mirabegron.
longest.duration.of.treatment.for.all.trials.included.was.12. was.more.effective.than.placebo.in.treating.OAB.by.decreas-
weeks..It.was.found.that.trospium.40.mg,.oxybutynin.topical. ing.the.mean.number.of.incontinence.episodes,.mean.num-
gel.100.mg/g,.and.fesoterodine.4.mg.had.the.most.favour- ber.of.micturition,.mean.volume.voided.per.micturition,.and.
able.efficacy/adverse.events.relationship,.while.higher.doses. mean.number.of.urgency.episodes.per.24.hours.(Level of
218
217
219
of.oral.oxybutynin.and.propiverine.had.the.least.favourable. evidence 1a, Grade A). .The.trials,.SCORPIO, .ARIES, .
(Level of evidence 1a, Grade A). 209 CAPRICORN, 220 .and.178-CL-048 221 .were.all.of.12.weeks.
duration..The.overall.treatment-emergent.adverse.events.
Safety, tolerability, and persistence (TEAEs).of.hypertension,.cardiac.arrhythmias,.and.urinary.
retention,.and.discontinuation.rates.were.similar.between.
The.most.common.adverse.events.reported.in.a.meta-analy- mirabegron.and.placebo..A.pooled.efficacy.analysis.of.these.
sis.was.dry.mouth.(29.6%.and.7.9%.of.active.treatment.and. trials.also.found.that.mirabegron.50.and.100.mg.decreased.
placebo.arm.patients).followed.by.pruritus.(Level of evidence the.number.of.incontinence.episodes.and.micturitions.per.
207
1a, Grade A). .The.most.commonly.adverse.events.reported. 24.hours.compared.to.placebo (Level of evidence 1a, Grade
groups.are.gastrointestinal,.followed.by.neurological,.ocu- A). .The.NICE.2013.report.also.indicates.that.mirabegron.
222
lar,.and.renal/genitourinary (Level of evidence 1a, Grade 50.mg.has.a.significant.improvement.in.urinary.frequency.
A). .A.network.meta-analysis.comparing.adverse.events.of. and.incontinence.episodes.compared.to.placebo (Level of
209
223
AMs.identified.82.reports,.with.most.of.them.being.parallel. evidence 1a, Grade A). .A.post-hoc.responder.analysis.of.
and.placebo-controlled..They.found.that.the.overall.adverse. pooled.data.from.three.phase.3.RCT.showed.that.patient.
event.profile.was.comparable.for.darifenacin,.fesoterodine,. reported.outcomes.(PROs).were.significantly.improved.com-
224
transdermal.oxybutynin,.propiverine,.solifenacin,.tolterod- pared.to.placebo (Level of evidence 1a, Grade A). .
ine,.and.trospium..However.oral.oxybutynin,.in.doses.of.or. In.an.incontinent.population.at.baseline,.a.post-hoc.analy-
exceeding.10.mg/day.was.associated.with.the.worst.adverse. sis.of.pooled.data.from.three.randomized.phase.3.trials.found.
event.profile.(Level of evidence 1a, Grade A). 210 that.mirabegron.50.mg.statistically.significantly.reduced.the.
Although.drug.persistence.is.generally.low.in.chronic. mean.number.of.incontinence.episodes,.micturitions,.and.
diseases,.AM.have.an.overall.poor.adherence.profile,.with. urgency.episodes.per.24.hours,.and.improved.mean.volume.
17‒35%.of.patients.still.taking.their.prescribed.drug.at.one. voided.per.micturition..The.treatment.effect.was.positively.
year. 211-213 .A.better.tolerability.profile.may.increase.rates.for. correlated.with.increasing.severity.of.incontinence.at.base-
75
long-term.treatment.of.OAB. line.(Level of evidence 1a, Grade A). .A.post-hoc.analysis.of.
AMs.are.contraindicated.in.patients.with.uncontrolled. SCORPIO.showed.similar.efficacy.in.subgroups.of.patients.
narrow-angle.glaucoma.due.to.their.antagonistic.actions.on. who.were.AM-naïve.and.those.with.prior.use.of.AM (Level
M3.and.M5.receptors.in.the.eye..The.anticholinergic.action. of evidence 1b, Grade B). 225
can.induce.or.precipitate.acute.angle-closure.glaucoma. . There.were.two.phase.3.trials.that.included.a.tolterodine.
214
AMs.contribute.to.the.overall.anticholinergic.burden.. 4.mg.active.treatment.arm..The.SCORPIO.study.compared.
Anticholinergic.burden.has.been.linked.to.cognitive.dys- tolterodine.to.placebo,.but.did.not.make.any.direct.com-
218
215
function.(Level of evidence 1b, Grade B), .but.also.with. parison.between.mirabegron.and.tolterodine. .Yamaguchi.
increased.mortality.and.cardiovascular.risk.(Level of evidence et.al.randomized.OAB.patients.to.placebo,.mirabegron.50.
216
1b, Grade B). .These.effects.should.be.considered.in.the. mg,.and.tolterodine.4.mg,.but.did.not.test.for.non-inferiority.
potential.use.of.a.medication.for.a.prolonged.duration.of.time.. of.efficacy.and.safety. 226
There.are.limited.long-term.data.on.the.use.of.AM.and.their. The.12-month.safety.and.efficacy.was.evaluated.in.a.
effect.in.different.patient.populations,.particularly.the.elderly. randomized,.double-blind,.active.controlled.phase.3.study..
Patients.received.either.mirabegron.50.or.100.mg.or.toltero-
Beta-3 adrenoceptor agonist dine.4.mg..Although.there.was.no.placebo.arm,.efficacy.was.
maintained.in.each.treatment.group.throughout.12.months,.
The.only.commercially.available.agent,.mirabegron,.is. as.determined.by.the.change.from.baseline.in.number.of.
approved.in.Canada.for.the.treatment.of.OAB..It.activates. micturitions.per.24.hours,.mean.number.of.incontinence.
beta-3.adrenoceptors,.allowing.bladder.relaxation,.improv- episodes.per.24.hours,.and.improvements.in.mean.volume.
ing.bladder.filling.and.storage.of.urine..A.starting.dose.of.25. voided.per.micturition.(Level of evidence 1b, Grade B). 227
mg,.and.increasing.to.50.mg.is.recommended..The.lowest.
dose.is.also.recommended.for.renal.and.hepatic.impairment..

E154 CUAJ • May 2017 • Volume 11, Issue 5