DrugsForIPF:Nintedanib (Ofev)

RobertHallowell,M.D.AssistantProfessorofMedicine

HarvardMedicalSchoolDirector,PulmonaryPractice,BIDMC

Disclosures

• Nofinancialdisclosures

Nintedanib (Ofev)

• (BIBF1120)• FDAapprovedOctober2014

+

TNFa

IL-1MCP-1

Fibrocytes Fibroblasts

TGFbFGF-R

PDGF

VEGF-R

Myofibroblasts

Collagen(Fibrosis)

Airspacelining

?

Nintedanib

NEngl JMed.2014;370(22):2071

INPULSIS-1:513patients(309drug;204placebo)FVCdecline(52weeks):−114.7mlvs −239.9(p<0.001)Timetofirstexacerbation:HR1.15(P=0.67)

INPULSIS-2:548patients(329drug;219placebo)FVCdeline (52weeks):−113.6mlvs −207.3(p<0.001)Timetofirstexacerbation:HR0.38(P=0.005)

TheINPULSIStrials

TheINPULSIStrials

NEngl JMed.2014;370(22):2071

ExacerbationRate

NEngl JMed.2014;370(22):2071

INPULSIS1

INPULSIS2

Cumulative

Exacerbatio

nrate

Days

INPULSIS-ON

• PatientsfromINPULSISwereeligibletocontinuetreatmentwithOFEV(open-label)

• 734/1061originalpatientsenrolled

• 430continuingOfev;304 hadbeenonplacebo

• Stillongoing

Crestani etal.Long-termnintedanib treatmentinidiopathicpulmonaryfibrosis(IPF):newdatafromINPUSIS-ON.Oralpresentationat:27th AnnualEuropeanRespiratorySocietyInternationalCongress.September9-13,2017;Milan,Italy.

TheprotectiveeffectsofOfev persistbeyond52weeks

AnnualFVCDecline

Ofev Placebo

INPULSIS(52WEEKS)

-113.6

-223.5

INPULSIS-ON(144WEEKS)

ContinuingOfev

StartingOfev

-142.6-112.4

~80%relativeriskreductioninexacerbation(INPULSIS2+INPULSIS-ON)

Ofev reducesacuteexacerbations

Crestani etal.Long-termnintedanib treatmentinidiopathicpulmonaryfibrosis(IPF):newdatafromINPUSIS-ON.Oralpresentationat:27th AnnualEuropeanRespiratorySocietyInternationalCongress.September9-13,2017;Milan,Italy.

CommonSideEffects

Diarrhea(62%)

Nausea(24%)Abdominalpain(15%)Vomiting(12%)Decreasedappetite(11%)

NEngl JMed.2014;370(22):2083

Only4%stoppedOfev duetodiarrhea(INPULSIS)

Dealingwithsideeffects

Dealingwithsideeffects

Takeeachdosewithameallargeenoughtofeelfull

Spaceeachdosebyafull12hours(Skipadoseifyouaremorethan1hlate)

TakeImodiumatthefirstsignofdiarrhea(Cangetuptothreefreeboxes)

Nursesupportoverthephone24/7

Assistancetofindlocalsocialsupport

AneducationalclasswithaClinicalEducator

Combinationtherapy?

Barriers:CostMoreGIsideeffectsHardtoshowefficacyPirfenidone decreasesnintedinib levels

IPFinvolvesdisregulation ofmultiple,complexpathways.

Eur Respir J2015;45:1382–1392

SpecialThanks

• ElaineTriano-Kim• TiaHubert• MaryLeroy-Sullivan

Questions?