11/7/2014

www.medscape.com/viewarticle/834204_print

www.medscape.com

TiotropiumShowingPromiseinPediatricAsthma
JimKling

October31,2014

AUSTINInchildrenwithpoorlycontrolledasthma,oncedailytiotropiumdeliveredwiththeRespimatinhaler
improveslungfunctionwhenaddedtoinhaledcorticosteroids,withnoapparentchangeinadverseeffects,new
researchhasshown.
Thedruganddevicecombinationisapprovedforthetreatmentofchronicobstructivepulmonarydisease(COPD),and
themanufacturer,BoehringerIngelheim,isexploringUSFoodandDrugAdministrationapprovalforasthma.
Anticholinergicmedicationshavelongbeenusedtotreatacuteasthmaattacks,butrecentevidencesuggeststhatthey
couldbeusefulasmaintenancetherapyinrefractorypatients.
"ThatgotBoehringerIngelheiminterestedinlookingattheasthmapartofthis,notjustCOPD,"saidMark
Vandewalker,MD,principalinvestigatorforclinicalresearchatTheOzarksinColumbia,Missouri.Hepresentedthe
researchhereatCHEST2014.
Inadultswithasthma,thecombinationisaneffectiveaddontoinhaledcorticosteroids(NEnglJMed.2012367:1198
1207),sothisstudylookedspecificallyatapediatricpopulation.
The48weekphase3trialinvolvedadolescentswhohadasthmaforatleast3months,aforcedexpiratoryvolumein
1second(FEV)predictedof60%to90%,andascoreofatleast1.5ontheAsthmaControlQuestionnaire6point
scale.
Theagerangewas12to17years,65%ofthecohortwasmale,meanasthmadurationwas7.86years,andmean
baselineFEV%predictedwas82.8.
Participantshadnotsmokedinthepreviousyearorhadneversmoked.Theywererandomizedtoreceiveoncedaily
tiotropium,either5gor2.5g,orplacebo,alldeliveredwiththeRespimatinhaler.Thedrugwasgivenasanaddon
toinhaledcorticosteroids,indosesofbudesonide200to400gorequivalentfor12to14yearsoldsand400to
800gfor14to17yearsolds.
TheprimaryendpointwaspeakFEVinthe3hoursafterdosingatweek24.Thesecondaryendpointwastrough
(predose)FEVatweek24,whichwasmeasured10minutesbeforereceivingthatday'sdose.FEVpeakinthe3
hoursafterthedosingandtroughresponseswerealsomeasuredatweek48.
Table1.PeakFEVforTiotropiumComparedWithPlacebo

Variable

AdjustedMeanDifference(mL)

PValue

Tiotropium5g

Week24FEVareaunderthecurve

174

.0005

Week48FEV3hoursafterdosing

174

.0006

Tiotropium2.5g

Week24FEVareaunderthecurve

134

.0085

Week48FEV3hoursafterdosing

176

.0007

http://www.medscape.com/viewarticle/834204_print

1/3

11/7/2014

www.medscape.com/viewarticle/834204_print

Table2.TroughFEVforTiotropiumComparedWithPlacebo

TroughFEV

AdjustedMeanDifference(mL)

PValue

Tiotropium5g

Week24

117

.0320

Week48

157

.0044

Tiotropium2.5g

Week24

ns

Week48

137

.0154

Theadverseeventprofilewassimilarinallthreegroups,exceptthereweresomedifferencesindrugrelatedadverse
eventsandheadache.
"Youmightthinkdrymouthwouldbeaconcern,andsofarithasn'tbeen,"saidDrVandewalker."Mythoughtisthat
that'sduetotheRespimatdevice.WedoseedrymouthwiththeolderHandiHalerdevice."
Table3.IncidenceofAdverseEvents

AdverseEvents

Tiotropium5g(n=134),%

Tiotropium2.5g(n=125),%

Placebo(n=138),%

Oneormore

62.7

63.2

59.4

Severe

1.5

1.6

2.2

Drugrelated

3.0

0.8

0.7

Headache

6.7

5.6

1.4

Forchildrenwhoseasthmaisnotundercontrol,thedrugcouldbeausefuloption."Itlookslikeitwasabeneficial
treatment.Sofar,theteenagersarerespondinginamannersimilartoadultsinfactmorerobustlywhichwekind
ofexpectbecausetheyhaven'thadasthmaquiteaslong,sohavelessdamagetotheirairways.Thesafetyprofilehas
beenasgoodas,ifnotbetterthan,thatseeninadults,"DrVandewalkeradded.
Thedrugwouldbeawelcomeadditiontopediatricasthmacare,accordingtoChrisCarroll,MD,fromtheUniversityof
ConnecticutinHartford,whoattendedtheposterpresentation.
"Forchildrenwithrefractoryasthmawhoareonmoderatesteroidsandnotwellcontrolled,itwouldbereallyniceto
haveotheroptions.It'sgreatthatthey'redoingpediatricstudiesbecauseforalotofmedications,theydon'tbother,"he
toldMedscapeMedicalNews.
Hesaidhefindsthedatareassuring."Idon'thaveanyspecificconcernsaboutsafetyforthismedication,"DrCarroll
said.
http://www.medscape.com/viewarticle/834204_print

2/3

11/7/2014

www.medscape.com/viewarticle/834204_print

ThisstudywasfundedbyBoehringerIngelheim.DrVandewalkerhasreceivedresearchreportfromthecompany.Dr
Carrolldisclosednorelevantfinancialrelationships.
CHEST2014:AmericanCollegeofChestPhysiciansMeeting:Abstract1994584.PresentedOctober29,2014.
MedscapeMedicalNews2014WebMD,LLC
Sendcommentsandnewstipstonews@medscape.net.
Citethisarticle:TiotropiumShowingPromiseinPediatricAsthma.Medscape.Oct31,2014.

http://www.medscape.com/viewarticle/834204_print

3/3