ACTIVETUBERCULOSISINPATIENTSWITHINFLAMMATORYBOWELDISEASEAFTERTREATMENTWITH ANTI-TNFTHERAPY.

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ACTIVETUBERCULOSISINPATIENTSWITHINFLAMMATORYBOWELDISEASEAFTERTREATMENTWITH ANTI-TNFTHERAPY.

ACTIVETUBERCULOSISINPATIENTSWITHINFLAMMATORYBOWELDISEASEAFTERTREATMENTWITH ANTI-TNFTHERAPY.

Introduction:Anti-tumournecrosisfactoragents(anti–TNFs)representmajoradvancesinthemanagementof inflammatoryboweldisease(IBD)howevertheyareassociatedwithafive-foldincreasedriskofMycobacterium tuberculosis(TB)infectionintreatedpatients.Assuch,allpatientsshouldbescreenedforlatentTBinfection(LTBI)prior toanti-TNFtherapy.Inthisstudy,wereviewedcasesofactiveTBinfectionwhichdevelopedafteranti-TNFtoidentifyrisk factorsandlessonstobelearned.
Methods:AllpatientswithIBDwhoweretreatedwithanti-TNFbetweenMarch2007andNovember2015wereidentified frompharmacyrecords.ThosewhodevelopedactiveTBwereidentifiedfromtheLondonTBregister.Clinicaland electronicnoteswerereviewedandthefollowingdatawascollected:demographics,LTBIscreening,TBriskfactors, presentationdiagnosisandmanagementofactiveTB,anti-TNFandotherimmunosuppressivetherapy.Thescreening protocolwasupdateIDuringthestudyperiod;priortoJuly2013screeningwasundertakenwithafullhistory,CXRand tuberculinskintest(TST).AfterthisdatetheTSTwasreplacedwithaQuantiferonGoldAssay.
Results:Of732patientstreatedwithanti-TNF,sixpatientswerediagnosedwithactiveTB.Afurtherpatientwasinitially diagnosedwithTBbutlatergrewtheatypicalmycobacteria,M.chelonae.FivepatientshadCrohn’sdiseaseandonehad UlcerativeColitis.ThreepatientsweremaleandallpatientswereHIVnegative.AgeatTBdiagnosisrangedfrom24to
40years.(Ethnicity,placeofbirthwillbeaIDed)
ThreepatientswerereceivingAdalimumab(ADA)therapyatthetimeofTBdiagnosisandtwowerereceivingInfliximab (IFX).AllpatientstakingADAhadpreviouslybeentreatedwithIFX.Twopatientswereonanti-TNFaloneatTBdiagnosis andtheremainingthreeweretakingatleastoneotherimmunosuppressiveagent.Timefrominitiationofanti-TNF treatmenttoTBdiagnosisrangedfromthreetoforty-onemonths(median13,IQR=3).Onepatientwasnotreceivinganti- TNFtherapyatthetimeofTBdiagnosisbuthadreceivedtreatmentwithIFXthreemonthsprior.
ThreepatientshadcultureconfirmedTB,onepatientwasMTBcomplexPCRpositivebutculturenegativeandtwo patientsweretreatedforpresumedTBonthebasisofclinicalandradiologicalfeatures.Allisolatedcultureswerefully sensitivetofirst-linetherapy.
TwopatientspresentedwithmiliaryTB,twohadabdominaldisease,onehadpleuro-pulmonaryTBandonepatient presentedwithbothpulmonaryandpericardialTB.Treatmentdurationwasforbetweensixandtwelvemonthsdepending onthesiteandseverityofdisease.Fivepatientscompletedtreatment,fortheremainingpatienttreatmentwasongoing. ThreepatientshadpriorBCGvaccinations,onepatienthadnotbeenvaccinatedandthevaccinationstatusoftwopatientswasunknown.FourpatientshadnegativeTSTspriortoanti-TNFtreatment(threewereonimmunosuppressives atthistime).OnepatientwasscreenedwithaQuantiferontest,(whileonimmunosuppressives),theresultwas indeterminate.TwopatientsdidnothaveevidenceofTSTorQuantiferonscreeningpriortoanti-TNF.Allpatientshad normalchestimagingpriortoinitiatingtherapy,howeverinonly3caseswasthiswithin3monthspriortoinitiating treatment.NoneofthesepatientswereconsiderhighriskandwerenottreatedforLTBIpriortoanti-TNF.

Conclusion:ThisworkhighlightsthechallengesofLTBIscreenbeforestartinganti-TNFandthepotentialforpatientsto developactiveTBwithoutobviousriskfactors.SomeareasofLondon(includingthoseinthecatchmentareaofour centre)haveaTBprevalenceofatleasttwicethe40/100,000designatedashighprevalencebytheWHO.Ithighlights theriskoffalsenegativeresults,particularlyinimmunosuppressedpatients.Itisnotablethatnoneofthepatientswere consideredhighriskforTBanIDidnotreceiveLTBItreatment.
Giventhatsomepatientsscreenedmayreceiveprolongedandrecurrentcoursesofanti-TNF,werecommenIDiscussion aroundwhenpatientsshouldberescreened.InthesepatientswhodevelopedactiveTB,itisnotclearwherethisis reactivationoflatentTBordenovoinfection.Itmaybethatrescreening,mayhaveidentifiedLTBIbeforethepatients developedactiveTB.TheeffectofQuantiferonbasedscreeningprotocolsoncasesofactiveTBwillbere-evaluated oncetheprotocolhasbeeninuseforalongerduration.
HoweveritisimportanttoacknowledgethatitwillneverbepossibletopreventallcasesofactiveTB,thereforealongside comprehensivescreeningmethods,theremustbecontinuedfocusonensuringpromptdiagnosisandtreatmentofTBin atriskpatients.Thisisfacilitatedbyclosecollaborationwithlocalrespiratoryandinfectiousdiseasesservices.

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