course material

1. ACTIVETUBERCULOSISINPATIENTSWITHINFLAMMATORYBOWELDISEASEA
FTERTREATMENTWITH ANTI-TNFTHERAPY.
ACTIVETUBERCULOSISINPATIENTSWITHINFLAMMATORYBOWELDISEASEAFTERTREATM
ENTWITH ANTI-
TNFTHERAPY.ACTIVETUBERCULOSISINPATIENTSWITHINFLAMMATORYBOWELDISEASE
AFTERTREATMENTWITH ANTI-TNFTHERAPY.Introduction:Anti-
tumournecrosisfactoragents(anti– TNFs)representmajoradvancesinthemanagementof
inflammatoryboweldisease(IBD)howevertheyareassociatedwithafive-
foldincreasedriskofMycobacterium
tuberculosis(TB)infectionintreatedpatients.Assuch,allpatientsshouldbescreenedforlatentTB
infection(LTBI)prior toanti-
TNFtherapy.Inthisstudy,wereviewedcasesofactiveTBinfectionwhichdevelopedafteranti-
TNFtoidentifyrisk
factorsandlessonstobelearned.Methods:AllpatientswithIBDwhoweretreatedwithanti-
TNFbetweenMarch2007andNovember2015wereidentified
frompharmacyrecords.ThosewhodevelopedactiveTBwereidentifiedfromtheLondonTBregist
er.Clinicaland
electronicnoteswerereviewedandthefollowingdatawascollected:demographics,LTBIscreeni
ng,TBriskfactors, presentationdiagnosisandmanagementofactiveTB,anti-
TNFandotherimmunosuppressivetherapy.Thescreening
protocolwasupdateIDuringthestudyperiod;priortoJuly2013screeningwasundertakenwithaf
ullhistory,CXRand
tuberculinskintest(TST).AfterthisdatetheTSTwasreplacedwithaQuantiferonGoldAssay.Resul
ts:Of732patientstreatedwithanti-
TNF,sixpatientswerediagnosedwithactiveTB.Afurtherpatientwasinitially
diagnosedwithTBbutlatergrewtheatypicalmycobacteria,M.chelonae.FivepatientshadCrohn’
sdiseaseandonehad
UlcerativeColitis.ThreepatientsweremaleandallpatientswereHIVnegative.AgeatTBdiagnosis
rangedfrom24to40years.(Ethnicity,placeofbirthwillbeaIDed)ThreepatientswerereceivingAd
alimumab(ADA)therapyatthetimeofTBdiagnosisandtwowerereceivingInfliximab
(IFX).AllpatientstakingADAhadpreviouslybeentreatedwithIFX.Twopatientswereonanti-
TNFaloneatTBdiagnosis
andtheremainingthreeweretakingatleastoneotherimmunosuppressiveagent.Timefrominitia

2. tionofanti-TNF treatmenttoTBdiagnosisrangedfromthreetoforty-
onemonths(median13,IQR=3).Onepatientwasnotreceivinganti-
TNFtherapyatthetimeofTBdiagnosisbuthadreceivedtreatmentwithIFXthreemonthsprior.Thr
eepatientshadcultureconfirmedTB,onepatientwasMTBcomplexPCRpositivebutculturenegati
veandtwo
patientsweretreatedforpresumedTBonthebasisofclinicalandradiologicalfeatures.Allisolated
cultureswerefully sensitivetofirst-
linetherapy.TwopatientspresentedwithmiliaryTB,twohadabdominaldisease,onehadpleuro-
pulmonaryTBandonepatient
presentedwithbothpulmonaryandpericardialTB.Treatmentdurationwasforbetweensixandt
welvemonthsdepending
onthesiteandseverityofdisease.Fivepatientscompletedtreatment,fortheremainingpatienttre
atmentwasongoing.
ThreepatientshadpriorBCGvaccinations,onepatienthadnotbeenvaccinatedandthevaccinatio
nstatusoftwopatientswasunknown.FourpatientshadnegativeTSTspriortoanti-
TNFtreatment(threewereonimmunosuppressives
atthistime).OnepatientwasscreenedwithaQuantiferontest,(whileonimmunosuppressives),th
eresultwas
indeterminate.TwopatientsdidnothaveevidenceofTSTorQuantiferonscreeningpriortoanti-
TNF.Allpatientshad
normalchestimagingpriortoinitiatingtherapy,howeverinonly3caseswasthiswithin3monthsp
riortoinitiating
treatment.NoneofthesepatientswereconsiderhighriskandwerenottreatedforLTBIpriortoanti
-TNF.Conclusion:ThisworkhighlightsthechallengesofLTBIscreenbeforestartinganti-
TNFandthepotentialforpatientsto
developactiveTBwithoutobviousriskfactors.SomeareasofLondon(includingthoseinthecatch
mentareaofour
centre)haveaTBprevalenceofatleasttwicethe40/100,000designatedashighprevalencebythe
WHO.Ithighlights
theriskoffalsenegativeresults,particularlyinimmunosuppressedpatients.Itisnotablethatnone
ofthepatientswere
consideredhighriskforTBanIDidnotreceiveLTBItreatment.Giventhatsomepatientsscreenedm
ayreceiveprolongedandrecurrentcoursesofanti-TNF,werecommenIDiscussion
aroundwhenpatientsshouldberescreened.InthesepatientswhodevelopedactiveTB,itisnotclea
rwherethisis
reactivationoflatentTBordenovoinfection.Itmaybethatrescreening,mayhaveidentifiedLTBIb
eforethepatients
developedactiveTB.TheeffectofQuantiferonbasedscreeningprotocolsoncasesofactiveTBwillb
ere-evaluated
oncetheprotocolhasbeeninuseforalongerduration.Howeveritisimportanttoacknowledgethat
itwillneverbepossibletopreventallcasesofactiveTB,thereforealongside
comprehensivescreeningmethods,theremustbecontinuedfocusonensuringpromptdiagnosis
andtreatmentofTBin

3. atriskpatients.Thisisfacilitatedbyclosecollaborationwithlocalrespiratoryandinfectiousdiseas
esservices.DisclosureofInterest:NoneDeclared