A budget optimization analysis for the treatment and potential elimination of hepatitis C virus infection in the United States

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1 A budget optimiztion nlysis for the tretment nd potentil elimintion of heptitis C virus infection in the United Sttes SAT-295 Olivier Ethgen,2, Yuri Snchez Gonzlez 3, Jordn J. Feld 4 SERFAN innovtion, Nmur, Belgium; 2 University of Liège, Liège, Belgium; 3 AbbVie Inc., North Chicgo, IL, USA; 4 Toronto Centre for Liver Disese, Toronto, ON, Cnd Presented t the Europen Assocition for the Study of the Liver (EASL), April 9 23, 27, Amsterdm, Netherlnds Despite growing body of evidence on the cost effectiveness of novel heptitis C virus () tretments,2, there is need to: (i) ssist helthcre pyers in the identifiction of the best strtegy tht optimizes the use of their vilble budgets for tretment, nd (ii) inform whether these investments cn brek even in foreseeble future nd secure pth towrds elimintion As the totl budget llocted to tret in the United Sttes (US) is expected to fll, 3 it is importnt to inform optiml tretment policies to substntite the public helth vlue of investments in tretment To identify optiml therpeutic strtegies on the bsis of most fvorble ptient outcomes, subject to specified budget constrint nd epidemiology To ssess whether up-front investments in tretment could be recouped by society with future lower medicl spending nd improved qulity-djusted survivl, nd identify the potentil time to brek even MODEL DESIGN A sequentil, multi-cohort, helth-stte trnsition Mrkov model (Figure ) ws designed to ssess the clinicl nd economic outcomes for the US dignosed popultion from 27 until 23 The model used nnul cycles for the eligible popultion dignosed cross the five Metvir fibrosis stges (F F4) An incident cohort of newly dignosed ptients ws dded nnully nd djusted proportionlly to the size of the totl popultion over time Figure. Model Schemtic Tretment efficcy Fibrosis stge distribu on F.7% SVR 2 F F3 SVR 2 F4 95.% 95.% 95.% 95.% 9.%.35 b.7 b.39 b F 35.7% DCC.85 b F2.2 b F3.6 b 23.2% 4.3%.25 b.6 b.3 b.3 b.3 b Annul trnsition probbility subsequent to Yer. Sources: Rein DB, et l. Clin Infect Dis. 25; 5;6(2):57-68; b Thein HH, et l. Heptology. 28; 48(2):48-3. D, ll-cuse deth; DCC, decompensted cirrhosis; F, Metvir fibrosis score; HCC, heptocellulr crcinom; LrD, liver-relted deth (ie, deth from DCC, HCC, nd LT); LT, liver trnsplnt; SVR 2, sustined virologic response 2 weeks fter tretment. Tble. Tretment Strtegies Strtegies Strtegy LT LrD.4 b.38 b HCC.25 b.49 b.49 b F4 6.% D D D D D Fibrosis Stges F F F2 F3 F4 Description No tretment t ll Strtegy 2 Tret F only Strtegy 3 Tret F-F only Strtegy 4 Tret F-F-F2 only Strtegy 5 Tret F-F-F2-F3 only Strtegy 6 Tret F-F-F2-F3-F4 Strtegy 7 Tret F-F2-F3-F4 only Strtegy 8 Tret F2-F3-F4 only Strtegy 9 Tret F3-F4 only Strtegy Tret F4 only Strtegy Tret F-F-F2-F3-F4 sequentilly Strtegy 2 Tret F4-F3-F2-F-F sequentilly TREATMENT STRATEGIES AND BUDGET ALLOCATION 2 tretment strtegies encompssing possible tretment lloction by fibrosis stge were considered (Tble ) Strtegies to ssumed budget lloction cross different fibrosis groups proportionl to the fibrosis distribution in the popultion Strtegies nd 2 ssumed the sequentil tretment of ptients until the vilble budget ws fully exhusted by either treting ptients with F first (F F4) or treting ptients with F4 first (F4 F) DATA INPUTS Dt inputs relted to the nturl history nd tretment efficcy re denoted in Figure Epidemiologic dt nd cost inputs re described in Tble 2 Cost inputs were obtined from published literture nd included tretment costs, helthcre expenditures ttributble to liver-relted complictions (including decompensted cirrhosis [DCC], heptocellulr crcinom [HCC], liver trnsplnt [LT] nd liver-relted deth [LrD]) nd extrheptic mnifesttions (EHMs) ssocited with infection (Tble 2) Tble 2. Dt Inputs Dt Input Bse Dt Input Bse Prevlence 27 Costs Prevlent cses in 27 3,5, Tretment c $8, Frction dignosed b 5% Medicl (nnul costs) ge (yers) c 5 SVR F F3 e $225 Annul incidence SVR F4 e $225 Annul incident cses d 2, F / F / F2 / F3 e $753 Frction dignosed b 5% F4 (CC) e $,433 ge (yers) c 5 DCC g $33,34 Helth stte utilities e HCC st yer e $4,663 SVR F F3.93 HCC sub. yer e $4,663 SVR F4 f.827 LT st yer e $9,3 F.86 LT sub. yer e $34,369 F.86 LrD h $25, F2.86 EHMs i $2, F3.83 F4 (CC).8 DCC.7 HCC.67 LT.78 Refers to prior to trnsplnt helth stte. Sources nd ssumptions: Edlin BR, et l. Heptology. 25;62(5): b Yehi BR, et l. PLoS One. 24; 9(7): e554. c Assumption. d Heptitis C Online - Epidemiology in the US e Rein DB, et l. Clin Infect Dis. 25; 5;6(2): f Multiplier from Leidner AJ, et l. Heptology. 25;6(6):86-9. g McAdm-Mrx C, et l. J Mng Cre Phrm. 2;7: h Dieguez et l. AASLD Orl Presenttion 26. i Reu et l. 27 (AbbVie dt on file H7. DOF.6). CC, compensted cirrhosis (Metvir fibrosis score F4); DCC, decompensted cirrhosis; EHMs, extrheptic mnifesttions; F, Metvir fibrosis score; HCC, heptocellulr crcinom; LrD, liver-relted deth (ie, deth from DCC, HCC, nd LT); LT, liver trnsplnt; SVR, sustined virologic response. Drug costs were computed bsed on the list price of ll-orl direct-cting ntivirl therpies nd verged t $8, per tretment course Qulity-djusted life yers (QALYs) were estimted bsed on utility weights used in previous US-bsed helth economic nd public helth ssessments 4,5 Ptient outcomes nd costs were discounted t 3% OUTCOMES Helth outcomes included the projected number of QALYs, ptients treted nd ptients reching sustined virologic response (SVR), end-stge liver disese (ie, DCC, HCC or LT) or LrD Economic outcomes included tretment costs, medicl (liver-relted nd extrheptic) costs nd the vlue of improved ptient outcomes (estimted t $, per QALY gined 6 ) Time to brek even ws mesured s the number of yers required for up-front investments in tretment to be fully recovered with the vlue of QALYs gined nd/or with reduced medicl costs in the future ANALYSES First, we ssessed the optiml tretment strtegy tht chieved the best possible liver outcomes (ie, highest number of SVRs nd QALYs nd lowest number of DCC, HCC, LT nd LrD cses) The nnul tretment budget ws ssumed to decline by 5% per yer from $ billion in 27 to $5. billion in 23 Second, we ssessed the pth to elimintion with the optiml tretment strtegy under two budget expnsion scenrios: Annul tretment budget of $ billion mintined throughout (ie, no nnul budget decline) Annul tretment budget incresed to $5 billion nd mintined throughout Finlly, we ssessed the time to brek even for n up-front investment to tret ll fibrosis stges in 27, reltive to the optiml tretment strtegy bsed on $5 billion nnul budget throughout We considered this nlysis from two helthcre perspectives: Pyer perspective vluing improved ptient outcomes t $ per QALY Socil perspective vluing improved ptient outcomes t $, per QALY OPTIMAL TREATMENT: STEPWISE TREATMENT F4 F (STRATEGY 2) Among ll budget-fesible tretment options, the stepwise strtegy to sequentilly tret ll fibrosis stges prioritizing the most dvnces cses (F4 F) mximized fvorble liver outcomes nd minimized dverse liver outcomes by 23 (Tble 3) In contrst, the next best strtegy of restricting tretment to stges F3 F4 yielded 29,54 fewer SVR cses, 65,734 fewer QALYs nd n increse of 2,5 DCC, 4,62 HCC, 2,92 LT nd 2,8 LrD cses Tble 3. Impct of Budget Expnsion With the Optiml Tretment Strtegy Budget SVR, n DCC, n HCC, n LT, n LrD, n QALYs, n Budget declining 5% nnully Figure 2. Pth to Elimintion Under 3 Budget Scenrios (F4 F, Strtegy 2) 4, 2,, 8, 6, 4, 2, 4, 2,, 8, 6, 4, 2, 2, 8, 6, 4, 2,, 8, 6, 4, 2, 25, ,75 2,83 7,72,83 Treted p ents with 96,723 9,886 BENEFITS OF BUDGET EXPANSION UNDER THE OPTIMAL STEPWISE STRATEGY F4 F (FIGURE 2) Sustining the tretment budget t $ billion throughout improved popultion helth outcomes nd ccelerted the pth towrds disese elimintion compred with declining budget An incresed nd sustined tretment budget of $5 billion throughout chieved the best popultion helth outcomes nd lowest totl cost since the greter up-front investments in tretment were fully offset by future svings in medicl nd EHMs costs (Tble 3) BREAK-EVEN ANALYSIS FOR INVESTMENTS TO TREAT ALL FIBROSIS STAGES IMMEDIATELY (FIGURE 3) From pyer s perspective, n up-front investment to tret ll fibrosis stges in 27 would cost $4 billion but brek even by 228 nd generte net surplus of $37 billion by 23 From socil perspective tht vlues ech QALY gined t $,, this $4 billion up-front investment would brek even by 223 nd generte net surplus of $.35 trillion by 23 87, F F F2 F3 F4 Treted p ents with 25, 25, 25, 25, 25, 25, 25, 25, 25, 25, 25, 25, 25, 82,928 78,78 Tretment Costs, bn Liver-relted Costs, bn EHMs Costs, bn Totl Costs, bn,26,729 23,663 39,684 5,4 43,645 4,59,756 $87.2 $9.6 $63. $269.9 Fixed $ bn budget,53,328 23,57 38,29 4,98 42,47 4,56,993 $6. $8.7 $46.3 $28. Fixed $5 bn budget,643,655 8,76 32,836 3,95 34,94 4,345,37 $24.6 $5.5 $9.7 $249.8 bn, billion; DCC, decompensted cirrhosis; EHMs, extrheptic mnifesttions; HCC, heptocellulr crcinom; liver-relted deth (ie, deth from DCC, HCC, nd LT), LrD; LT, liver trnsplnt; QALYs, qulity-djusted life yers; SVR, sustined virologic response. Outcomes mesured over ,842 7, 67,545 64,68 9, F F F2 F3 F4 87,5 87,5 87,5 87,5 87,5 87,5 87,5 87,5 87, bn=billion; F=Metvir fibrosis score; =heptitis C virus. Treted p ents with F F F2 F3 F4 7,52 Budget declining 5% nnully ($bn in 27, $5.bn in 23) Budget mintined t $bn throughout Budget incresed to $5bn throughout ,,,8,,6,,4,,2,,, 8, 6, 4, 2, 2,,,8,,6,,4,,2,,, 8, 6, 4, 2, 2,,,8,,6,,4,,2,,, 8, 6, 4, 2, Figure 3. Brek-even Anlysis $,6,,, $,4,,, $,2,,, $,,,, $8,,, $6,,, $4,,, $2,,, $ $2,,, $4,,, $6,,,,75, 27,75, 27,75, 27,629,829,52,94,46,9,35,627 Dignosed p ents with,28,466,25, ,629,829,54,853,399,852,28,62,35,886 95,7 F F F2 F3 F4 Dignosed p ents with,62,353,42, ,577,4,45,856,228,873,5,58 Tret ll F F4 in 27 vs Strtegy 2: with $5bn nnul budget throughout Socil perspec ve (improved p ent outcomes vlued t $, per QALY) Pyer perspec ve (improved p ent outcomes vlued t $ per QALY) bn=billion; F=Metvir fibrosis score; =heptitis C virus; QALY=qulity-dusted life yer. 868,4 789,332 74,64 642, , ,54 799,78 F F F2 F3 F4 Dignosed p ents with 87,35 69, ,79 556, ,666 33,44 9, ,48 332,262 F F F2 F3 F4 52,6 83,479 8,53 77,95 75, As the sequentil tretment of ll fibrosis stges prioritizing most dvnces cses chieves the most fvorble ptient outcomes, tretment restrictions by fibrosis stge yields suboptiml number of SVR cses, QALYs nd dverse liver events If the current declining budget trends continue, our model suggests tht there would be more thn.5 million dignosed cses in 23 tretment budgets should therefore be incresed nd sustined if the World Helth Orgniztion gol to cure 8% of cses by 23 7 is to be met Incresed investment to tret cn be cost-sving. Treting ll fibrosis stges immeditely would yield positive return to pyers within yers, nd to society within 6 yers. While this effort would require n up-front investment of $4 billion, the net economic benefits to society could exceed $ trillion by 23 SVR inputs my differ from rtes observed in rel-world settings Trnsition probbilities nd costs were obtined from estimtes in the literture; ctul vlues for these my differ cross other settings nd ptient subgroups The model did not ccount for trnsmission, reinfection, tretment complince, retretment or dditionl fctors relted to chronic infection While tretment costs were ssumed constnt over time, llowing for price erosion would further ccelerte the pth to elimintion nd time to brek even The model only focused on the dignosed popultion. Further nlyses re needed to identify the optiml policies for the undignosed popultion regrding screening, testing nd linkge to cre With incresed nd sustined levels of investment, the sequentil tretment of ll fibrosis stges prioritizing the most dvnced cses provides the highest helth benefits nd fstest pth to elimintion in the US Incresed efforts to tret ll ptients dignosed with immeditely could finncilly brek even in 6 yers nd provide significnt net economic benefits to pyers nd society therefter Design, study conduct nd finncil support for the study were provided by AbbVie Inc. AbbVie Inc. prticipted in the interprettion of dt, nd review nd pprovl of the poster. All uthors contributed to the development of the publiction nd mintined control over the finl content. Conflicts of Interest: Olivier Ethgen owns SERFAN innovtion nd is consultnt for AbbVie Inc. Yuri Snchez Gonzlez is n employee of AbbVie Inc. nd my own stocks nd/or options of the compny. Jordn Feld hs received consulting fees from AbbVie Inc., Giled, Jnssen nd Merck, nd reserch support from AbbVie Inc., Giled, Jnssen, Merck nd Regulus. Editoril support for poster development ws provided by Tom Owen, PhD, of Fishwck Fcilitte, nd funded by AbbVie.. Sb S, et l. J Med Econ. 26;9(8): Chhtwl J, et l. Clin Gstroenterol Heptol. 26;pii: S (6) Express Scripts 26 Commericl Drug Trend Report. Avilble t ccessed Februry Rein DB, et l. Clin Infect Dis. 25; 5;6(2): Leidner AJ, et l. Heptology. 25;6(6): Murphy KM, Topel RH. J Pol Econ. 26;4(5): World Helth Orgniztion. Globl Report on Access to Heptitis C Tretment. Focus on Overcoming Brriers. October 26. Avilble t: ccessed Februry 27.

2 The cumultive prevlence nd incidence of extr-heptic mnifesttions in ptients with heptitis C virus infection: rel-world evidence from the United Sttes SAT-26 Nncy Reu, Frncis Vekemn 2, Eric Wu 2, Ynjun Bo 3, Yuri Snchez Gonzlez 3 Rush University Medicl Center, Chicgo, IL; 2 Anlysis Group, Inc., Boston, MA; 3 AbbVie Inc., North Chicgo, IL, USA Presented t the Europen Assocition for the Study of the Liver (EASL), April 9 23, 27, Amsterdm, Netherlnds Between 2.7 nd 3.9 million people re currently living with chronic heptitis C virus () infection in the United Sttes (US) Previous studies hve shown tht infection is ssocited with both heptic complictions (eg, cirrhosis, liver filure) nd extr-heptic mnifesttions ([EHMs] eg, chronic kidney disese [CKD], crdiovsculr disese) 2-5 No previous study hs ssessed how the prevlence of comprehensive list of potentil EHMs chnges over time nd compred such differences between ptients with vs those without OBJECTIVE To compre the 5-yer cumultive prevlence nd incidence of EHMs mong ptients with nd without in the US DATA SOURCE Optum Clims Dt - Clinformtics Dt Mrt (//29 3//26; US), de-identified helth clims dtset, including ptients medicl, prescription drug, lbortory, nd eligibility informtion Ptients included: cohort comprised of ll dult ptients with dignosis code for chronic (Interntionl Clssifiction of Disese, Ninth Revision [ICD-9] dignosis codes 7.44 nd 7.54; ICD- dignosis code B8.2; N = 64,25); no- cohort comprised of rndom smple of the generl dult popultion (N = 5,) from which ptients with dignosis codes for chronic were excluded STUDY DESIGN AND STUDY COHORTS Retrospective nlysis of the cumultive prevlence nd incidence of EHMs using longitudinl clims dt Two cohorts mtched : on ge, sex, region, nd yers of follow-up: nd no- cohorts (exct mtch; see Figure for cohort selection nd definition of index dte) The index dte ws selected s the dy of first dignosis for the cohort nd the first dy of insurnce eligibility for the no- cohort Figure. Selection of nd no- study cohorts nd demogrphic chrcteristics P ents with dignosis for chronic N=64,25 P ents with 2 dignoses for chronic (index dte= dte of the first dignosis for chronic ) N=43,277 Optum Clims Dt- Clinform cs Dt mrk from Q 29 to Q 26 Rndom smple of the generl popul on N=5, P ents with no dignosis for chronic (index dte= dte of helthcre eligibility or //29) N=498,43 P ents ged 8 yers of the index dte P ents ged 8 yers of the index dte N=43,99 N=379,43 : exct mtching on ge, sex, region, nd yers of post-indes follow-up The prevlence of ny EHM in the st yer post-index dte ws 6% in the cohort nd 35% in the no- cohort (prevlence OR: 2.7; Figure 2), nd it incresed by the 5 th yer to cumultive prevlence of 86% nd 66%, respectively (prevlence OR: 3.3; Figure 3); the 4-yer incidence of ny EHM ws 65% nd 48%, respectively (incidence OR: 2.; Figure 4) Alredy in the st yer post-index, the cohort hd significntly higher prevlence of EHMs thn the no- cohort; this erly difference is likely due to the fct tht ptients in the cohort were infected before the dignosis nd hd n incresed risk of EHM prior to the index dte A similr trend with higher prevlence in the vs the no- cohort ws lso observed for specific EHMs, including for conditions previously not recognized s EHMs such s inflmmtory bowel disese nd gstroesophgel reflux disese (prevlence OR in 5 th yer post-index: 2.4 nd 2., respectively; Figure 3) Figure 2. Prevlence of 2 EHMs mong vs no- cohorts in the st yer post-index (by order of frequency in cohort) Any EHM Chronic f gue syndrome/f gue Gstroesophgel reflux disese Type II dibetes Crdiovsculr diseses Depression Fibromylgi Chronic kidney disese (CKD) Nephri s/nephro c syndrome/nephrosis Psorisis Irritble bowel syndrome Inflmmtory bowel disese Non-Hodgkin s lymphom Prostte cncer Insulin resistnce Cogni ve Impirment Hed nd neck cncers Thyroid cncer Celic Prkinson s disese Esophgel cncer Higher EHM prevlence in thn no- EHM prevlence vs no- 59.5% vs 35.% (OR=2.7) 9.5% vs.3% (OR=2.) 9.% vs 8.4% (OR=2.5) 6.5% vs.% (OR=.6) 6.% vs 7.2% (OR=2.5).4% vs 3.7% (OR=3.4) 5.8% vs 3.7% (OR=.6) 4.% vs.2% (OR=3.4) 3.% vs.5% (OR=5.9).9% vs.% (OR=.7).7% vs.% (OR=.7).7% vs.5% (OR=3.2).9% vs.3% (OR=2.9).9% vs.9% (OR=.9).7% vs.6% (OR=.2).4% vs.% (OR=5.).4% vs.% (OR=3.4).2% vs.2% (OR=.9).2% vs.% (OR=.7).% vs.% (OR=.2).% vs.% (OR=-) Prevlence OR vs no- (95%) ST YEAR Prevlence OR could not be clculted (t st yer post-index there were 2 ptients with esophgel cncer in the cohort vs none in the no- cohort) Figure 3. Prevlence of 2 EHMs mong versus no- cohorts in the 5 th yer post-index (by order of frequency in cohort) Higher EHM prevlence in thn no- EHM prevlence vs no- Incident cses continued to ccumulte from the 2 nd to 5 th yer post-index even for EHMs tht hd very high prevlence in the st yer post-index (Figure 5) Some severe nd reltively uncommon conditions in the generl popultion, such s CKD, reched prevlence of >% mong the popultion in the 5 th yer post-index (Figure 5) Some EHMs tht re more chrcteristic of older popultions (eg, cognitive impirment, Prkinson s disese, nd cncer) hd low prevlence in both study cohorts; this could be explined by the fct tht the cohorts included reltively young ptients (medin ge 53 yers) Figure 4. Cumultive prevlent nd incident cses of ny EHM from the st to the 5 th yer post-index P ents, N p < Prevlence OR=2.7,634 2,398 2,68,44 Cumul ve incidence from 2 nd to 5 th yer post-index: 65% in vs 48% in no- cohorts (OR=2.) Incidence OR=.9 Prevlence OR=2.9, ,398 2,4 478,44 Prevlent cses crried over from previous yer Incident cses in the yer EHM-free cses in the yer Incidence OR=.8 Prevlence OR=3. Incidence OR=.8 Prevlence OR=3.2 Prevlent cses in the yer Incidence OR=.5 Prevlence OR=3.3 No- No- No- No- No- st YEAR 2 nd YEAR 3 rd YEAR 4 th YEAR 5 th YEAR Figure 5. Prevlent nd incident cses of selected specific EHMs in the 5 th yer post-index ,878,82 338, ,66, , ,339, ,453 In light of the growing EHM risks ssocited with infection, current restrictions on tretment ccess bsed on fibrosis stge my excerbte the clinicl burden to ptients nd economic burden to pyers in both the short nd long terms The gp in EHMs observed in ptients with s erly s their yer of dignosis not only persists but increses over time compred with ptients without. This suggests potentil role for timely dignosis, linkge to cre, nd erly tretment to close this gp The study smple comprised of commercilly-insured ptients my not be representtive of the generl popultion Some ptients included in the no- cohort could be -infected but not yet dignosed, nd thus the prevlence OR of EHMs could hve been underestimted The nd no- cohorts were mtched on ge, sex, region, nd durtion of follow-up; however, residul confounding due to other fctors ssocited with infection (eg, riskier behviors in the cohort) my persist This study ws subject to the limittions of retrospective studies bsed on helthcre clims dt, including occsionl errors or clim omissions. However, such limittions would likely ffect both nd no- cohorts similrly The extent to which the excess EHM risk of finncilly burdens the helthcre system or cn be mitigted with effective tretment remins n re of further reserch Further reserch is lso needed on the best policies to close the existing EHM gps between nd no- ptients, which my involve trgeted screening, dequte linkge to cre, nd tretment upon dignosis regrdless of fibrosis stge EHMs pose high clinicl burden on ptients with, which grows over time nd could trnslte into substntil economic burden Expnded screening nd erly tretment my help reduce the risk of EHMs ssocited with by closing the gp in EHM prevlence nd delying the incidence of EHMs The results of the current study my be prticulrly relevnt to inform therpeutic nd policy decisions relted to screening, linkge to cre, nd tretment upon dignosis or t erly fibrosis stges P ents mtched on ge, sex, region, nd yers of post-index follow-up N=43,99 P ents with 5 yers of post-index follow-up N=4,32 COHORT N=4,32 Age (yers), Men ± SD [Medin] Femle, % Region, % Northest Midwest South West Treted for during the 5 yers post-index, % 52 ± 8 [53] 64% 9% 7% 55% 9% 33% P ents mtched on ge, sex, region, nd yers of post-index follow-up N=43,47 P ents with 5 yers of post-index follow-up N=4,32 NO- COHORT N=4,32 Age (yers), Men ± SD [Medin] Femle, % Region, % Northest Midwest South West Treted for during the 5 yers post-index, % 52 ± 8 [53] 64% tretment included: boceprevir, dcltsvir, dsbuvir, elbsvir, grzoprevir, interferons lph, ledipsvir, ombitsvir, pritprevir, ribrvin, ritonvir, simeprevir, sofosbuvir, telprevir OUTCOMES AND STATISTICAL ANALYSES Twenty EHMs were investigted bsed on globl literture review 6 (Figure 2) To ssess the evolution of EHM risks over time, EHM prevlence, defined s the proportion of ptients living with given EHM t given point in time, ws mesured for ech of the 2 EHMs in the st nd 5 th yer post-index Cumultive incident cses (ie, newly dignosed) from the 2 nd to 5 th yer postindex were lso reported Prevlence odds rtios (ORs) were estimted from undjusted conditionl logistic regression models tht ccount for mtching; incidence ORs were estimted from logistic regression models djusted for the ge, sex, nd region (mtching did not hold in the subgroup of ptients t risk fter the st yer post-index) 9% 7% 55% 9% n/ Any EHM Chronic f gue syndrome/f gue Gstroesophgel reflux disese Crdiovsculr diseses Type II dibetes Depression Fibromylgi Chronic kidney disese (CKD) Nephri s/nephro c syndrome/nephrosis Irritble bowel syndrome Psorisis Inflmmtory bowel disese Cogni ve Impirment Insulin resistnce Prostte cncer Non-Hodgkin s lymphom Hed nd neck cncers Celic Thyroid cncer Prkinson s disese Esophgel cncer Prevlence OR vs no- (95%) 5 TH YEAR 86.% vs 65.9% (OR=3.3) 48.% vs 32.7% (OR=.9) 4.2% vs 24.5% (OR=2.) 4.% vs 23.3% (OR=2.2) 27.3% vs 8.8% (OR=.7) 26.5% vs.8% (OR=2.9) 9.% vs.4% (OR=.9).7% vs 4.4% (OR=2.6) 9.8% vs 2.6% (OR=3.9) 4.5% vs 3.2% (OR=.4) 4.3% vs 2.7% (OR=.6) 3.% vs.3% (OR=2.4) 2.2% vs.8% (OR=2.6) 2.% vs 2.% (OR=.9).8% vs.9% (OR=.9).8% vs.8% (OR=2.2).% vs.6% (OR=.8).8% vs.4% (OR=.8).4% vs.4% (OR=.).3% vs.2% (OR=.2).% vs.% (OR=-) Prevlence OR could not be clculted (t 5 th yer post-index there were 3 ptients with esophgel cncer in the cohort vs none in the no- cohort) Cumul ve number of prevlent EHM cses from st to 5 th yer post-index 3 2 2,96,5 2, , , No- No- No- No- Chronic f gue Gstroesophgel syndrome/f gue reflux disese 2, , Crdiovsculr disese 2,933 3, Type II dibetes 5 th YEAR Prevlent cses in the st yer post-index Cumul ve incident cses from the 2 nd to the 5 th yer post-index EHM-free cses EHMs with prevlence > % in t lest one cohort in the 5 th yer post-index 647 2,962 3,264 3,557 3,573 3,6 3, No- Depression No- Fibromylgi No- Chronic kidney disese Prevlent cses in the 5 th yer post-index Funding for this reserch ws provided by AbbVie Inc.; the study sponsor ws involved in ll stges of the study reserch nd mnuscript preprtion. Nncy Reu is n employee of Rush University Medicl Center nd is consultnt for AbbVie Inc. She is lso consultnt for Giled Sciences, Inc., Merck nd Co, Inc., nd Bristol-Myers Squibb, nd her institution hs received reserch support from AbbVie Inc. nd Giled Sciences, Inc. Eric Wu is n employee of Anlysis Group which received consultncy fees from AbbVie Inc. for conducting reserch nlysis. Frncis Vekemn ws n employee of Anlysis Group t the time this nlysis ws conducted. Ynjun Bo nd Yuri Snchez Gonzlez re employees of AbbVie Inc. nd my own AbbVie stock or stock options. Rluc Ionescu-Ittu, Willy Wynnt, nd Hel Romdhni, employees of Anlysis Group, Inc., contributed to the dt nlysis. AbbVie provided funding to Anlysis Group for this work.. Centers for Disese Control nd Prevention (CDC). Heptitis C FAQs for Helth Professionls. Avilble t: Accessed Februry Ccoub P, et l. Arthritis Rheum. 999;42(): Ccoub P, et l. Ther Adv Infect Dis. 26;3(): Voulgris T, Sevstinos VA. Hept Res Tret. 26; doi:.55/26/ Epub 26 Jn Younossi Z, et l. Gstroenterology. 26;5(7): Nuño Solinís R, et l. Infect Dis Ther. 26; doi:.7/s x. Epub 26 Oct 25.

3 Effect of heptitis C tretment with ombitsvir/pritprevir/ritonvir + dsbuvir regimen on ptient s helth-relted qulity of life: Anlysis of Phse 3 nd Phse 3b clinicl trils SAT-268 Smmy Sb, Drshn Meht 2,3, Stcie Hudgens 4, Nthn Grunow 4, Ynjun Bo 3, Brett Pinsky 3 Dvid Geffen School of Medicine, University of Cliforni, Los Angeles, Los Angeles, CA, USA; 2 Scheffer Center for Helth Policy nd Economics, University of Southern Cliforni, Los Angeles, CA, USA; 3 Helth Economics nd Outcomes Reserch, AbbVie Inc., North Chicgo, IL, USA; 4 Clinicl Outcomes Solutions, Tucson, AZ, USA Presented t the Europen Assocition for the Study of the Liver (EASL), April 9 23, 27, Amsterdm, Netherlnds Chronic heptitis C (CHC)-infected ptients hve diminished helth-relted qulity of life (HRQoL), 4 prticulrly driven by ftigue 5 9 Ptients treted with n interferon (IFN)- nd ribvirin (RBV)- bsed regimen reported significnt decrese in their HRQoL prior to nd during tretment IFN- nd RBV-free regimens comprising of combintion of direct cting ntivirls (DAAs) hve been pproved by the FDA for certin genotypes (GT) of heptitis C virus () ptients. Prior ptient-reported outcome (PRO) studies on these DAA regimens hve demonstrted n improvement in HRQoL during the tretment period. This improvement ws seen until 24 weeks post-tretment 3 Bsed on ner % sustined virl response (SVR)2 rtes observed in clinicl trils, the ombitsvir/pritprevir (identified by AbbVie nd Ennt)/ritonvir + dsbuvir (3D) regimen ws recently pproved for use without RBV for GTb ptients with or without compensted cirrhosis 4 The impct of tretment with the 3D regimen for this specific popultion is not well defined This study ims to report on the impct of tretment with the 3D regimen on ptient-reported function nd qulity of life s mesured by the 36-Item Short Form Helth Survey (SF-36) nd the EuroQol five dimensions questionnire (EQ-5D) nd ftigue subscle (FS) for GTb ptients during tretment nd up to 52 weeks post-tretment STUDY DESIGN The study pooled nd nlyzed PROs from: Six registrtionl Phse 3 trils (Phse 3 study popultion) SAPPHIRE I 5, SAPPHIRE II 6, PEARL II 7 /III/IV 8, TURQUOISE II 9 PRO dt collected: SF-36 nd EQ-5D Two Phse 3b trils (Phse 3b study popultion) TOPAZ I (NCT22949) nd TOPAZ II (NCT267945) PRO dt collected: SF-36 nd FS of Functionl Assessment of Chronic Illness Therpy-Ftigue (FACIT-F) Ptient selection is described in Figure The study period comprised of the tretment period nd 48 or 52 weeks of post-tretment follow-up for Phse 3 nd 3b trils, respectively PRO QUESTIONNAIRES PRO questionnires utilized in this study re described in Tble Tble. PRO Questionnires Figure. Ptient Selection Note: Six Phse 3 trils (Phse 3 study popultion): SAPPHIRE I 5, SAPPHIRE II 6, PEARL II 7 /III/IV 8, TURQUOISE II 9. Two Phse 3b trils (Phse 3b study popultion): TOPAZ I (NCT22949) nd TOPAZ II (NCT267945) DATA ANALYSIS Empiricl Anlysis: Mixed Models PRO scores t ech time point were nlyzed using liner mixed models independently for Phse 3 nd Phse 3b study popultions Models were djusted for: Fixed effects: Bseline PRO domin score, region, bseline virl lod, tretment durtion, tretment by time interction, prior tretment history, bseline fibrosis stges, ptient s ge, nd history of drug use Rndom effects: Study enrollment The chnge from bseline ws predicted bsed on the model coefficients nd tested for sttisticl significnce Minimlly Importnt Difference (MID) Chnges: Proportionl Anlysis A comprtive nlysis of the proportion of the study popultions chieving MID on PRO vribles ws performed t tretment week 4, post-tretment week 2, nd the end of follow-up (post-tretment week 48/52) Bsed on prior published -specific literture, cliniclly meningful improvements were defined s increses of: 2 points on SF-36 mentl nd physicl component score 3 points on the SF-36 component domin score, except VT domin 4.2 points on VT domin 23 3 points on FS of FACIT-F 24 Mesure Description Scoring SF-36v2 Totl of 36 items trgeting functionl helth nd well-being 2 EQ-5D-5L FS The two mjor components nd contributing domins re: Physicl component summry score: physicl functioning (PF), role physicl (RP), bodily pin (BP), nd generl helth (GH) Mentl component summry score: vitlity (VT), socil functioning (SF), role emotionl (RE), nd mentl helth (MH) SF-36 VT domin hs been regrded s the most comprehensive well-being mesure for ptient who suffers from 5,8, Comprises of 5 dimensions (mobility, self-cre, usul ctivities, pin/discomfort, nd nxiety/depression), ech of which is rted on 5 levels of severity 2 Responses to the 5 items re used to derive discrete helth stte tht is mpped to preference (utility) specific for different societies Prticipnts lso report their perception of their overll helth on seprte visul nlog scle (VAS) The totl scores on ech domin rnge from to Higher scores indicte better HRQoL The totl scores on EQ-5D-5L rnge from to nd on EQ-5D VAS rnge from to Higher scores indicte better HRQoL This is symptom-specific domin of the FACIT-F mesuring ftigue in vriety of chronic diseses or helth conditions 22 Totl scores rnge from to 52 Higher FS scores indicte lesser degree of ftigue EQ-5D-5L=EuroQol five dimensions questionnire with five-level scle; FACIT-F=Functionl Assessment of Chronic Illness Therpy-Ftigue; FS=ftigue subscle; HRQoL=helth-relted qulity of life; SF-36=36-Item Short Form Helth Survey; VT=vitlity. STUDY POPULATION A totl of 297 GTb ptients nd 895 GTb ptients from Phse 3 nd Phse 3b trils, respectively, were included for nlysis Bseline demogrphics of the study popultion re shown in Tble 2 PHASE 3A STUDY POPULATION (TABLE 3) Bseline HRQoL Bseline vlues of ech instrument were equivlent to those in the generl popultion Tretment Period HRQoL Across domins nd instruments, there were no sttisticl or cliniclly meningful declines in ptient HRQoL during the tretment period Ptients begn to report increses in HRQoL on mentl helth (MH) nd generl helth (GH) domins of SF-36 nd the helth utility index of EQ-5D tht were sttisticlly significnt by tretment week 4 Increses observed during the tretment period persisted during the post-tretment period Post-tretment HRQoL By post-tretment week 2, ptients reported increses in HRQoL scores versus bseline for the SF-36 mentl component score nd its domins, nd for EQ-5D. These increses from bseline were sttisticlly significnt By post-tretment week 48, there ws sttisticlly significnt increse cross domins nd instruments Tble 3. Longitudinl Mixed Model Results: Phse 3 Undjusted bseline vlue (SE) W4 (SE) Tble 2. Demogrphics of Study Popultion GTb popultion: RBV-free therpy Phse 3 study popultion (n=297) Phse 3b study popultion (n=895) Age, men (SD); yers 5.7 (.8) 5.9 (2.6) Femle 6 (54.%) 53 (57.3%) Rce White Blck Asin Others Region Austrli/New Zelnd nd others Europe North Americ/USA 274 (92.5%) 6 (5.4%) 3 (.%) 2 (.7%) 233 (78.5%) 64 (2.6%) 847 (94.6%) 28 (3.%) 8 (2.%) 2 (.2%) 65 (68.7%) 4 (5.8%) 39 (5.5%) Prior dibetes history (yes) 9 (6.4%) 42 (5.6%) Fibrosis Stge F F F2 F3 F4 Bseline virl lod 8, IU/mL 2 (67.6%) 66 (22.3%) 3 (.%) 66 (67.7%) 36 (5.2%) 5 (6.8%) 3 (.3%) 229 (77.%) 567 (63.5%) BMI 3 kg/m 2b 62 (2.9%) 5 (6.9%) Injection drug user (yes) 34 (.5%) HOMA-IR 3 c 7 (27.7%) 252 (3.6%) Tretment nïve 29 (7.4%) 454 (5.7%) P/R experienced 88 (29.6%) 44 (49.3%) Remining percentge represents no dibetes; b remining percentge represents <3 kg/m 2 ; c remining percentge represents <3. BMI=body mss index; =heptitis C virus; HOMA-IR=Homeostsis Model Assessment-Insulin Resistnce; P/R=peginterferon/ribvirin. EOT (SE) PTW2 (SE) EOF (SE) SF-36 MCS 5.47 (.59).4 (.38).4 (.48).67 (.49) 2.39 (.49) SF-36 Vitlity 55.6 (.59).72 (.4).5 (.5) 2.6 (.52) 2.84 (.52) SF-36 Socil Functioning 5.7 (.48).4 (.38).29 (.46).24 (.47).92 (.47) SF-36 Mentl Helth (.6).88 (.4).88 (.49).8 (.5) 2.64 (.5) SF-36 Role Emotionl (.56).9 (.42).63 (.49).62 (.5).28 (.5) SF-36 PCS 5.97 (.47).38 (.29).9 (.36).64 (.37).42 (.37) SF-36 Physicl Functioning 5.24 (.49).45 (.32).55 (.36).56 (.36).4 (.36) SF-36 Role Physicl 5.49 (.49).66 (.36).7 (.43).83 (.44).32 (.44) SF-36 Generl Helth 49.6 (.58).75 (.34).4 (.42).76 (.44) 2.76 (.44) SF-36 Bodily Pin (.58).2 (.46).35 (.54).47 (.55).84 (.55) EQ-5D HUI.88 (.). (.). (.6).2 (.).3 (.) EQ-5D VAS (.83).87 (.5) 2.35 (.65) 4.2 (.67) 5.46 (.67) p<.5. EOF=end of follow-up (48 weeks); EOT=end of tretment; HUI=helth utility index; MCS=mentl component summry score; PCS=physicl component summry score; PTW=post-tretment week; SE=stndrd error; VAS=visul nlogue scle; W=week. The tble presents predicted chnge selected time points from liner mixed models. The PRO scores t ech time point were nlyzed djusting for bseline PRO domin score, region, bseline virl lod, tretment durtion, tretment by time interction, prior tretment history, bseline fibrosis stge, ptient s ge, nd history of drug use s fixed effects. Study enrollment ws included s rndom effect. Study coefficients were not significnt, indicting no sttisticlly significnt vrition between studies. PHASE 3B STUDY POPULATION (TABLE 4) Bseline HRQoL Bseline vlues cross SF-36 domins nd component scores were lower thn those in the generl popultion Tretment Period HRQoL Across domins nd instruments there ws no sttisticl or cliniclly meningful decline in ptient HRQoL during the tretment period Ptients from Phse 3b trils begn to report n increse in HRQoL cross ll SF-36 domins by tretment week 4 Increses observed during the tretment period persisted during the post-tretment period Post-tretment HRQoL Ptients reported improvements on the SF-36 component scores t post-tretment weeks 2 nd 52 tht were sttisticlly significnt nd cliniclly meningful Tble 4. Longitudinl Mixed Model Results: Phse 3b Undjusted bseline vlue (SE) W4 (SE) EOT (SE) PTW2 (SE) EOF (SE) SF-36 MCS 47.9 (.38).76 (.25) 2.8 (.32) 3.53 (.35) 3.37 (.43) SF-36 Vitlity 5.27 (.36).62 (.25) 2.76 (.32) 4.82 (.35) 4.7 (.44) SF-36 Socil Functioning 47.5 (.35).67 (.25).95 (.3) 2.87 (.34) 2.7 (.4) SF-36 Mentl Helth 47.6 (.37).84 (.26) 2.2 (.32) 3.9 (.35) 3.7 (.43) SF-36 Role Emotionl (.38).57 (.28).99 (.34) 2.3 (.37) 2.9 (.45) SF-36 PCS 5.8 (.28).58 (.7).47 (.22) 2.8 (.24) 2.6 (.3) SF-36 Physicl Functioning (.29). (.8).94 (.23).6 (.25).78 (.3) SF-36 Role Physicl (.33).3 (.23).86 (.29) 2.8 (.3) 2.3 (.39) SF-36 Generl Helth (.33) 2.32 (.2) 3.69 (.26) 4.37 (.29) 4.33 (.36) SF-36 Bodily Pin 5.82 (.35).8 (.25).37 (.3) 2. (.34).68 (.42) FS (.35).2 (.23) 2.42 (.28) 3.89 (.32) 4.34 (.39) p<.5. EOF=end of follow-up (52 weeks); EOT=end of tretment; FS=ftigue subscle of FACIT-F; HUI=helth utility index; MCS=mentl component summry score; PCS=physicl component summry score; PTW=post-tretment week; SE=stndrd error; VAS=visul nlogue scle; W=week. The tble presents predicted chnge selected time points from liner mixed models. The PRO scores t ech time point were nlyzed djusting for bseline PRO domin score, region, bseline virl lod, tretment durtion, tretment by time interction, prior tretment history, bseline fibrosis stge, ptient s ge, nd history of drug use s fixed effects. Study enrollment ws included s rndom effect. Study coefficients were not significnt, indicting no sttisticlly significnt vrition between studies. MID Increse MID increses re shown for Phse 3 nd Phse 3b in Figures 2 nd 3, respectively The percentge of ptients experiencing cliniclly meningful chnges ws sustined nd improved during the post-tretment period Figure 2. MID Increses: Phse 3 Percentge of p ents ining MID increse (%) MCS MCS_MH MCS_RE MCS_SF MCS_VT PCS PCS_BP PCS_GH PCS_PF MCS domins PCS domins Error brs denote 95% confidence intervls. BP=bodily pin; GH=generl helth; MCS=mentl component summry score; MH=mentl helth; PCS=physicl component summry score; PF=physicl functioning; RE=role emotionl; RP=role physicl; SF=socil functioning; VT=vitlity. Figure 3. MID Increses: Phse 3b Percentge of p ents ining MID increse (%) End of tretment Post-tretment week 2 End of follow-up (post-tretment week 48) PCS_RP End of tretment Post-tretment week 2 End of follow-up (post-tretment week 52) MCS MCS_MH MCS_RE MCS_SF MCS_VT PCS PCS_BP PCS_GH PCS_PF PCS_RP FS MCS domins PCS domins FACIT-F Error brs denote 95% confidence intervls. BP=bodily pin; FS=ftigue score; GH=generl helth; MCS=mentl component summry score; MH=mentl helth; PCS=physicl component summry score; PF=physicl functioning; RE=role emotionl; RP=role physicl; SF=socil functioning; VT=vitlity. This study is the first comprehensive ssessment of GTb ptient experience during nd post-tretment with n RBV-free 3D regimen for CHC Ptients enrolled in Phse 3b trils hd lower bseline PRO score compred with ptients enrolled in Phse 3 trils. This my be one of the driving fctors for Phse 3b tril ptients demonstrting higher improvements t subsequent follow-up time points The GTb popultion, treted with the RBV-free 3D regimen, did not report decrements in their HRQoL during the tretment period, which re commonly ttributed with RBV Post-tretment, there were improvements in HRQoL tht were both cliniclly nd sttisticlly significnt. Domins with the lrgest improvements included the VT domin of SF-36 nd FS in FACIT-F Our results re consistent with HRQoL gins documented with 3, 25 other IFN/RBV-free DAA regimens STRENGTHS & STRENGTHS PRO instruments used in this study hve been vlidted nd used widely cross indictions nd geogrphies Results from these nlyses were unique in terms of the length of follow-up dt reported; PRO dt were collected until 48 weeks post-tretment for Phse 3 trils nd 52 weeks post-tretment for Phse 3b trils The current study did not include GTb cirrhotic ptients from TURQUOISE III tril, since this study imed to provide long-term HRQoL dt for the study popultion. The TURQUOISE III tril collected dt until 24 weeks post tretment The study smpled ptients enrolled in clinicl trils, therefore generlizbility to ptients in routine clinicl prctice my be limited; further rel-world studies my be wrrnted Unobservble fctors, not collected in the dtbse, my hve influenced results Due to the multicenter nture of the clinicl trils, bis might be incorported due to site-specific peculirities. Our mixed models controlled for study region to reduce this possibility This study demonstrtes tht tretment with RBV-free 3D regimen for hs positive impct on HRQoL in GTb ptient popultions tht is mintined t follow-up of 48 nd 52 weeks Design nd study conduct for the study were pproved by AbbVie Inc. AbbVie Inc. prticipted in the interprettion of dt nd review nd pprovl of the poster. All uthors contributed to the development of the publiction nd mintined control over the finl content. Conflicts of Interest: Smmy Sb: Consultnt to nd serves on speker bureu for AbbVie, BMS, Giled, Jnssen, nd Merck. Drshn Meht: Finncilly supported for grdute reserch work by AbbVie s prt of fellowship greement between AbbVie nd University of Southern Cliforni (USC). Brett Pinsky nd Ynjun Bo: Employees of AbbVie Inc. nd my own stocks nd/or options of the compny. Nthn Grunow nd Stcie Hudgens: Employees of Clinicl Outcomes Solutions hired by AbbVie Inc. to provide consulting services on this project. Editoril support for poster development ws provided by Rebecc Wylie of Fishwck Fcilitte nd funded by AbbVie.. Lori A, et l. Am J Phys Med Rehbil. 24;93: Kondo Y, et l. J Gstroenterol Heptol. 27;22: Sobhonslidsuk A, et l. World J Gstroenterol. 26;2: Gutteling JJ, et l. Aliment Phrmcol Ther. 26;23: Younossi ZM. Gstroenterology. 2;2: Gutteling JJ, et l. Psychosomtics. 2;5: Gutteling JJ, et l. Neth J Med. 27;65: Häuser W, et l. Clin Gstroenterol Heptol. 24;2: Yng SS, et l. Expert Rev Gstroenterol Heptol. 24;9:9 2.. Afendy A, et l. Aliment Phrmcol Ther. 29;3: Younossi ZM, et l. Heptology. 25;6: Younossi ZM, et l. Digestive Disese Week, Chicgo, IL, Younossi ZM, et l. Clin Gstroenterol Heptol. 23;2: Viekir Pk USFDA drug lbel. Updted 4/26. b543fe3-99-c6c-dcc5-8f5f9dfe6ee.xml. 5. Feld JJ, et l. N Engl J Med. 24;37: Zeuzem S, et l. N Engl J Med. 24;37: Andreone P, et l. Gstroenterology. 24;47: e. 8. Ferenci P, et l. N Engl J Med. 24;37: Poordd F, et l. N Engl J Med. 24;37: Wre JE, Sherbourne CD. Med Cre. 992;3: EQ-5D-5L User Guide. 5L_UserGuide_25.pdf. 22. Webster K, et l. Qul Life Res. 999;8: Spiegel B, et l. Heptology. 25;4: Nordin A, et l. BMC Med Res Methodol. 26;6: Younossi ZM, et l. J Heptol. 26;65:33 9.

4 Erly versus delyed heptitis C tretment provides incresed helth benefits t lower costs: A UK cost-effectiveness nlysis of genotypes nd 4 tretment-nïve ptients SAT-294 Yuri Snchez Gonzlez, Andy Ingrm, Clire Lindsy, Hélène Prisé 2, Suchin Virbhk 2 AbbVie Inc., North Chicgo, IL, USA; 2 Medicus Economics, Boston, MA, USA Presented t the Europen Assocition for the Study of the Liver (EASL), April 9 23, 27, Amsterdm, Netherlnds An estimted 24, people in the United Kingdom (UK) re chroniclly infected with heptitis C virus () disese progression cn occur over 2 5-yer period; 2 long-term sequele of chronic infection my include cirrhosis, liver decompenstion, heptocellulr crcinom (HCC), nd liver trnsplnttion (LT) 3,4 Ptients in erly-stge fibrosis my hve limited ccess to highly effective tretment The costs of disese progression nd complictions, including decompensted cirrhosis (DCC), HCC, nd LT, re mjor drivers of the economic burden of 5 While chievement of SVR is ssocited with reduced risk of liver-relted complictions, ptients who chieve SVR from more severe liver disese sttes hve been shown to continue to fce n excess risk of liver disese complictions including HCC, LT, nd liver-relted mortlity 6 Therefore, erly tretment is believed to reduce the overll downstrem medicl costs compred with tretment in lter disese stges 7 9 Recent studies hve demonstrted the cost-effectiveness of the 3D regimen of ombitsvir/pritprevir (identified by AbbVie nd Ennt)/ritonvir nd dsbuvir ± ribvirin (RBV) for tretment of genotype (GT) ptients, nd the 2D regimen of ombitsvir/pritprevir/ritonvir ± RBV for tretment of GT4 ptients, vs previous nd current stndrds of cre, However, the cost effectiveness of treting ptients in erlyvs lte-stge fibrosis with 3D or 2D is not well understood OBJECTIVE To determine the lifetime risks of liver-relted morbidity nd mortlity nd the cost-effectiveness of receiving tretment with AbbVie 3D or 2D regimens ± RBV t different fibrosis stges in the UK Figure. Model Structure MODEL DESIGN A Mrkov model of the nturl history of ws developed bsed on previous literture (Figure ), Trget popultion included tretment-nïve GT ptients treted with 3D ± RBV, nd tretment-nïve GT4 ptients treted with 2D ± RBV Comprtive nlyses were crried out for ptients in different disese sttes by METAVIR fibrosis: Mild (F F) Moderte (F2 F3) Compensted cirrhosis (F4) The model ws run over lifetime horizon with ptients entering the model t ech disese stte nd receiving tretment with 3D or 2D ± RBV Ptients with mild or moderte fibrosis who chieve SVR were ssumed to be cured Ptients with compensted cirrhosis were ssumed to fce n excess risk of HCC, even fter chieving SVR, but did not progress to DCC For ptients who chieve SVR, reinfection ws possible. Reinfected ptients were ssumed to trnsition bck to their respective fibrosis stte prior to chieving SVR nd then progress through the more severe helth sttes t the sme rte s untreted ptients Deth from liver disese (LrD) could occur from the DCC, HCC, nd LT sttes; deth from non-liver cuses could occur from ny stte Trnsition probbilities were derived from previously published cost-effectiveness studies (Tble ) Tble. Annul Trnsition Probbilities Fibrosis Progression, Mild/Moderte/CC Bse Probbility Mild to Moderte.25 Moderte to CC.37 Non-fibrosis Disese Progression Recovered, no, History of Severe Fibrosis (CC) to HCC b.2 CC to DCC c.39 CC to HCC (First Yer) c.4 POPULATION CHARACTERISTICS Bseline chrcteristics of the trget popultion were bsed on review of UK-bsed literture (Tble 2) Tble 2. Bseline Ptient Chrcteristics Bseline Chrcteristics Tretment-nïve GT/GT4 Popultion Mild (F ) 46% Moderte (F2 3) 44% CC (F4) % Men Age (in Yers) 4 Mle 7% Source: Hrtwell D et l. Helth Technol Assess. 2;5(7):i-xii, -2; Hrris KA, et l. J Med Virol. 999;58(2):27-3. TREATMENT EFFICACY Efficcy rtes were bsed on Phse 3 clinicl trils with 3D ± RBV for tretment of GT tretment-nïve ptients, nd on the Phse 2 PEARL-I clinicl tril with 2D ± RBV for tretment of GT4 tretment-nïve ptients (Tble 3) Tble 3. SVR Rtes from AbbVie Clinicl Trils Bseline Chrcteristics Mild (F ) Moderte (F2 3) OUTCOMES Helth outcome mesures included lifetime risks of DCC, HCC, LT, nd LrD Other outcome mesures included lifetime costs (i.e. drug nd medicl costs) nd qulity-djusted life yers (QALYs) Cost-effectiveness ws quntified s incrementl costeffectiveness rtios (ICERs) Direct costs by helth stte were mesured in UK pounds nd bsed on systemtic literture review (Tble 4) Costs nd outcomes (e.g., QALYs) were discounted t 3.5% Tble 4. Direct Costs of by Helth Stte CC (F4) GT 97.2% 97.2% 96.3% GT4 % % 97.9% GT sources: SAPPHIRE I 2 ; PEARL IV 3 ; TURQUOISE II 4 ; PEARL III 3. GT4 source: PEARL I (CSR dt). GT- nd GT4--infected ptients who were treted with 3D ± RBV nd 2D ± RBV, respectively, erlier in the disese hve lower lifetime risk of DCC, HCC, LT, nd LrD compred with ptients treted t lter fibrosis stges (Figure 2) Figure 2. Lifetime Risk of DCC, HCC, LT, nd LrD with Tretment t Different Fibrosis stges Percent of p ents ever reching (%) D ± RBV therpy in tretment-nïve GT p ents 2.% Figure 3. Lifetime Costs nd QALYs with 3D ± RBV Tretment (GT) / 2D ± RBV Tretment (GT4) t Different Fibrosis Stges CC (F4) Moderte (F2 F3) Mild (F F) Mild (F F) 7.3% DCC 4.3% 3.%.9% 54.5 HCC Moderte (F2 F3) CC (F4) Mild (F F) 36.8% 3.%.2%.8% Life me cost (,) LT.9% 7.4% LrD 45.2% Percent of p ents ever reching (%) D ± RBV therpy in tretment-nïve GT4 p ents.7% 6.4% 3.5% 2.7%.7%.24 Moderte (F2 F3) 36.9% 6.4% 2.9%.2%.7%.6% DCC HCC LT LrD CC (F4) COST EFFECTIVENESS In both GT nd GT4 tretment-nïve ptients, initition of tretment t more severe liver disese sttes resulted in greter lifetime costs nd lower QALYs (Figure 3) GT 44.6% Life me QALYS In the UK, the Ntionl Helth Service (NHS) opertes fixed-budget, centrlly-bsed, commissioning policy for tretments which limits the number of eligible ptients who cn receive direct-cting ntivirl therpy The eligible ptient popultion hs been previously restricted to include only ptients with more severe liver disese (METAVIR F3 nd F4) While ccess is now unrestricted in terms of fibrosis score (METAVIR F F4), the limiting step is the nnul cp (run rte) in ptients treted in order to keep within the budget threshold This nlysis justifies cost effectiveness rgument for expnding eligibility criteri to include erly stge tretment, but should be ccompnied by incresing cpcity (run rte) to tret ptients regrdless of fibrosis score SVR inputs re obtined from AbbVie clinicl trils nd my differ from rtes observed in rel-world setting Results for GT4 F4 ptients re imputed from the PEARL-I clinicl tril, s nlysis ws conducted prior to AGATE-I tril dt vilbility. SVR rtes were ssumed equl to GTb ptients treted with 2D + RBV for 24 weeks s there is no dt vilble for GT4 F4 ptients Trnsition probbilities nd costs were obtined from the best vilble estimtes in the literture; ctul vlues for these my differ cross other settings nd ptient subgroups While our findings re bsed on tretment-nïve ptients, similr results were obtined for tretmentexperienced ptients Results my not be generlizble to specific rel-world settings GT- nd GT4--infected ptients who re treted with 3D ± RBV nd 2D ± RBV erlier in the disese process hve reduced risk of liver-relted morbidity nd mortlity Tretment in erly fibrosis stges is not only costeffective, but lso dominnt strtegy s it provides greter QALY benefits t lower costs SVR, History of Mild Disese Mild, Chronic SVR, History of Moderte Moderte, Chronic SVR, History of Compensted Cirrhosis Compensted Cirrhosis, Chronic Heptocellulr Crcinom Mortlity Liver Trnsplnt DCC to HCC (First Yer) c.4 Liver Trnsplnt DCC to Liver Trnsplnt (First Yer) d.2 HCC to Liver Trnsplnt (First Yer) e.2 Liver-relted Mortlity DCC to Liver Deth c.3 Liver Trnsplnt to Liver Deth f.5 After Liver Trnsplnt to Liver Deth f.57 HCC First Yer to Liver Deth c.43 Vrible Annul Cost Mild 6 Moderte b 589 CC (Chronic ) b 94 SVR, no, history of mild fibrosis b 58 SVR, no, history of moderte fibrosis b 58 SVR, no, history of severe fibrosis (CC) b 586 DCC 2,333 CC (F4) Moderte (F2 F3) Mild (F F) Life me cost (,) GT Life me QALYS Erly tretment strtegies were cost effective, nd dominnt (more QALYs gined t lower cost) compred with treting t lter fibrosis stges (Tble 5) Design, study conduct nd finncil support for the study were provided by AbbVie, Inc. AbbVie Inc. prticipted in the interprettion of dt, nd review nd pprovl of the poster. All uthors contributed to the development of the publiction nd mintined control over the finl content. Yuri Snchez Gonzlez nd Clire Lindsy re employees of AbbVie Inc. nd my own stocks nd/or options of the compny. Andy Ingrm is contrctor t Abbvie Inc. Suchin Virbhk is employed by Medicus Economics LLC, which received pyment from AbbVie Inc. to undertke reserch. Hélène Prisé is contrctor to Medicus Economics LLC, which received pyment from AbbVie Inc. to undertke reserch. Editoril support for poster development ws provided by Tom Owen, PhD, of Fishwck Fcilitte, nd funded by AbbVie. Decompensted Cirrhosis Note: Helth sttes re depicted by ellipses, while rrows represent permissible trnsitions between helth sttes. Hshed rrows depict the possibility of chieving sustined virologic response (SVR). Dotted rrows depict potentil reinfection. Deth is possible from ny helth stte. Liver-relted deth is possible from decompensted cirrhosis, heptocellulr crcinom, nd liver trnsplnt. HCC Subsequent Yer to Liver Deth c.43 Virl Reinfection e. Sources: Shepherd J, et l. Helth Technol Assess. 27;:-25; b Crdoso AC, et l. J Heptol. 2;52(5):652-7; c Hrtwell D et l. Helth Technol Assess. 2;5(7):i-xii,-2; Fttovich G, et l. Gstroenterology. 997;2(2): ; d Hrtwell D et l. Helth Technol Assess. 2;5(7):i-xii, -2; Grieve R, et l. Gut. 26;55(9): ; Siebert U, et l. Gut. 23;52(3): ; e Expert opinion; f Grieve R, et l. Gut. 26;55(9): ; Bennett WG, et l. Ann Intern Med. 997;27(): HCC (first yer),99 HCC (subsequent yer),99 Liver trnsplnt (first yer) 49,749 Liver trnsplnt (subsequent yers),873 Sources: Hrtwell D et l. Helth Technol Assess. 2;5(7):i-xii, -2; b Bckx M et l. J Virl Hept. 24;2(3):28-5. Tble 5. Cost-Effectiveness Anlysis GT GT4 ICER vs CC ICER vs Moderte Dominnt Tretment Strtegy Mild (F F) 2,825,45 Mild dominnt Moderte (F2 F3) 3,856 Moderte dominnt Mild (F F) 2, Mild dominnt Moderte (F2 F3) 3,929 Moderte dominnt Dominnt = more QALYs t lower cost. ICER: Incrementl cost-effectiveness rtio, per QALY.. Ntionl Institute for Helth nd Cre Excellence Finl Apprisl Determintion, ombitsvir-pritprevir-ritonvir with or without dsbuvir for treting chronic heptitis C, October 25 ccessed Februry Shepherd J, et l. Helth Technol Assess 27;: Biggins SW, et l. Liver Trnspl 22;8: Seeff LB. Heptology 22;36:s35-s McAdm-Mrx C, et l. J Mng Cre Phrm 2;7: Perlmn BL, Trub N. Clin Infect Dis 2;52: Crdoso AC, et l. J Heptol 2;52: Veldt BJ, et l. Gut 24;53: Tnk A, et l. World J Gstroenterol 27;3: Sb S, et l. J Med Econ 26;9: Virbhk S, et l. J Med Econ 26;25: Feld JJ, et l. N Engl J Med 24;37(7): Ferenci P, et l. N Engl J Med 24;37(2): Poordd F, et l. N Engl J Med 24;37(2):973-82