MDR-TBELIMINATION:WHATWILLITCOST?

Emily A. Kendall, MD Assistant Professor, Infectious Diseases,

Johns Hopkins University School of Medicine

48th Union World Conference on Lung Health, Guadalajara, Mexico, 14 October, 2017

OUTLINE

  TrendsanddriversofMDR-TBepidemics

  Whatinterventionswilleliminationrequire?

  Atwhatprice?

  Aretheyworththecost?

Observed trends in DS and MDR TB

Drivers of MDR TB epidemics: What we know ◦ Acquisi(on:Treatmentofdrug-suscep(bleTBseedsMDRepidemics1,2◦ Transmission:TransmiAedMDRexceedsnewresistanceacquisi(on3,4,5

◦ Under-diagnosis:Failuretodiagnoseandtreatprolongstransmission◦  Ineffec(vetreatment:Prolongstransmissionandpromotes2nd-lineresistance◦ Recentspread:KnownMDRTBcontactsathighrisk6,7

1.  MenziesPlosMed20092.  RockwoodJID20173.  YangLancetID2016

4.  KendallLancetRespirMed20155.  WHOGlobalReport2016no(fica(ons6.  GrandjeanPlosMed2015

7.  Prajapa(PedsIntChildHealth2015

…SuggesAng a mulA-faceted approach ◦  Treatmentofdrug-suscep(bleTBseedsMDRepidemicsàBeAerDS-TBcontrolmayhelp◦  Transmissionexceedsnewresistanceacquisi(onàMustinterruptMDR-TBtransmission

◦  FailuretodiagnoseandtreatprolongstransmissionàXpertscale-up,casefinding◦  Ineffec(vetreatmentprolongstransmissionandpromotessecond-linedrugresistanceàSecond-lineDST,op(mizedregimens,treatmentmonitoring,beAerregimens

◦  Recenttransmissionpredominates;knownMDRTBcontactsathighriskàContacttracing,second-linepreven(vetherapy,biomarkersforprogression

As for DS-TB, mulAple strategies needed

 Componentsofdrug-suscep(bleTBelimina(on:

As for DS-TB, mulAple strategies needed

 ExampleofprojectedimpactofmoreMDR-TBtreatmentandamore-effec(veregimen,SoutheastAsia:

 (Repeatedly,modelinganalyseslikethisoneshowthatmoreandbeAerMDRtreatmentcanhavealargeimpact,buts(llwon’tgetustoelimina(ononitsown.)

Kendalletal,LancetRespirMed2017

MDR-TB requires a mulA-faceted approach ◦  Treatmentofdrug-suscep(bleTBseedsMDRepidemicsàBeAerDS-TBcontrolmayhelp◦  Transmissionexceedsnewresistanceacquisi(onàMustinterruptMDR-TBtransmission

◦  FailuretodiagnoseandtreatprolongstransmissionàXpertscale-up,casefinding◦  Ineffec(vetreatmentprolongstransmissionandpromotessecond-linedrugresistanceàSecond-lineDST,op(mizedregimens,treatmentmonitoring,beAerregimens

◦  Recenttransmissionpredominates;knownMDRTBcontactsathighriskàContacttracing,second-linepreven(vetherapy,biomarkersforprogression

Most-efficientcombina/onswilldependonlocalepidemiology&economics.

ProhibiAve costs of MDR-TB control?  RifampinDST:◦  GeneXpertIVmachine:$17,000,◦  $10perXpertMTB/RIFcartridge1

 MDR-TBtreatmentcourse,LIC:◦  median$3,3002

 Second-lineDST:◦  $100?(volumeandassay-dependent,laboratoryintensive)3

 Contactinves(ga(ons:◦  ~$10-100percontactscreened4

 Resultofcostsandcomplexity:under-u/liza/on◦  24%rifampinDSTcoverage,fornewTBdiagnoses2◦  23%MDR/RRno(fica(on,perincidentMDR/RRTBcases2

◦  36%second-lineDSTcoverage,forMDR/RRTBdiagnoses2

◦  ??screening,forMDRTBcontacts(7%ofunder-5[DS]TBcontactsreceivepreven(vetherapy)2

Budgets,30TBHBCs

DS MDR/RR

No(fica(ons,30TBHBCs

DS MDR/RR

1.  FINDnego(atedpricing2.  WHOGlobalReport20163.  VassallPLOSMed2011

4.  YadavAJTMH2014,SteffenPLOSOne2013,A(fSpringerplus2012,MandalakasThorax2013

Two perspecAves on acceptable cost, illustrated for a novel RR-TB regimen:

Fixedper-pa(entcosts

Regimen-anddura(on-dependentmanagement

costs

Drugcosts

Otherfixedcosts

1.Affordabilityperspec/ve,e.g.atwhatpricewouldbeEerdrugs/regimensbebudget-neutral?

Shorterregimenreducesmanagementcosts,freesresourcesfordrugs

Fixedper-pa(entcosts

Reducedmanagement

costs

Increaseinavailabledrugbudget

Otherfixedcosts

Oneyear Oneyear

$0

$2,000

$4,000

$6,000

$8,000

$10,000

$12,000

$14,000

$16,000

$18,000

DRC India SouthAfrica Russia

$980 $1,579$2,700

$4,745

$1,754$2,940

$14,591$16,242

Budget-neutralregimenprice,pertreatmentcourse

Currentaverageregimencost,2015standardofcare(reference)Novel6moMDRregimen;~50%lowerdelivery&monitoringcosts

Fixedper-pa(entcosts

Regimen-anddura(on-dependentmanagementcosts

Drugcosts

Otherfixedcosts Otherfixedcosts

Per-pa(entcostsdecreasewithdecliningincidence

Managementcost

sdecreasewith

dura(on

anddeclinefurt

herover(me

Time

Furtherincreasein

poten(aldrugspending

Increaseinavailabledrugbudget

ShorterandbeAerregimenalsoreducesincidenceandimproveshealthoutcomes

2.Costeffec/venessperspec/ve:• Over(me,beAerregimensreducenumberofpa(entsrequiringtreatment.• Reduc(onsinmorbidityandmortalityalsohavevalue.

Addi(onalvalueofimprovedhealthoutcomes

Time

$300/DALYaverted(120,1040)

Exampleofepidemiologicprojec(on:

…withmortalityandprevalenceprojec(onsthatwecantranslateintoDALYsaverted:

Actualepidemiologicprojec(onsusedforthisanalysisarebasedonKendalletal,PLOSMed2017

*InPeruandPhilippines,perFitzpatrickandFloydPharmcoeconomics2012,convertedto2015USD

Fixedper-pa(entcosts

Regimen-anddura(on-dependentmanagementcosts

Drugcosts

Otherfixedcosts Otherfixedcosts

Per-pa(entcostsdecreasewithdecliningincidence

Managementcost

sdecreasewith

dura(on

anddeclinefurt

herover(me

Time

Furtherincreasein

poten(aldrugspending

Increaseinavailabledrugbudget

ShorterandbeAerregimenalsoreducesincidenceandimproveshealthoutcomes

2.Costeffec/venessperspec/ve:• Over(me,beAerregimensreducenumberofpa(entsrequiringtreatment.• Reduc(onsinmorbidityandmortalityalsohavevalue.

Addi(onalvalueofimprovedhealthoutcomes

Time

$300/DALYaverted(120,1040)

Economic benefits to acAng now  Example:second-lineDST+regimenop(miza(on.

 Supposeit:◦  reducesriskofMDRtreatmentfailurefrom30%to20%,and

◦  reducesacquiredpre-XDR/XDR(costlytore-treat)from10%to5%.

40RRTBcases

12RRTBnotcured

!DST+regimenadjustmentswouldbecost-neutralat>$400/pa@ent

–evenbeforeaccoun(ngforthepreventedMDRandXDRtransmissions.

*Assumingthatretreatmentcosts$3000forMDRalone,$6000forpre-XDR/XDR

 …aswellasincreaseinvestmentsinMDR-TBnow.

ToeliminateMDRTB,wemustreducethecostofdiagnosisandeffec(vetreatment…

So what will MDR TB eliminaAon cost?  Ican’tnameaprice.◦  HardtocostglobalTBelimina(oneveninabsenceofdrugresistance◦  Dependsinpartonfuturetechnologicaladvances

 But…

So what will MDR TB eliminaAon cost?  MDRelimina(onrequiresamul(-prongedstrategy.◦  Wemustworktomakethesemoreaffordable◦  Understandlocalepidemicstoiden(fymostefficientpackages

 Sucheffortsmaybecost-effec(veorevencost-saving◦  givendownstreamcostsofnotdoingthem

 …Butwillstraincurrentbudgetsandcapacity.

 Globalcommitmentandinvestmentarerequired.

ü  Case-findingü  Contacttracingü  Preven(onü  Regimenselec(onü  Treatmentmonitoringü  Pa(entsupport

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