assessing the burden of illness of chronic hepatitis c and impact...

June 2019

Vol. 25 • No. 8, Sup.

Assessing the Burden of Illness of Chronic Hepatitis C and Impact of Direct-Acting Antiviral Use on Healthcare Costs in Medicaid

Supplement to The American Journal of Managed Care® © 2019 Managed Care & Healthcare Communications, LLC

› Annual per-person Medicaid healthcare costs attributed to hepatitis C virus infection are estimated to average $17,674 and range from $10,561 to $46,263.

› Total cumulative Medicaid spending on interferon-free direct-acting antivirals since 2013 is expected to be fully offset by total cumulative healthcare expenditure reductions by the end of 2019.

› The cost of a complete interferon-free direct-acting antiviral treatment course, at 2018 estimated net prices, can be expected to be fully offset by healthcare cost savings after only 16 months, on average, on a per-person basis.

HIGHLIGHTS

S U P P L E M E N TTHE AMERICAN JOURNAL OF MANAGED CARE®

®

JUNE 2019 www.ajmc.com


This supplement was supported by Pharmaceutical Research and Manufacturers of America.

Opinions expressed by authors, contributors, and advertisers are their own and not necessarily those of Managed Care & Healthcare Communications, LLC, the editorial staff, or any member of the editorial advisory board. Managed Care & Healthcare Communications, LLC, is not responsible for accuracy of dosages given in articles printed herein. The appearance of advertisements in this publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality, or safety. Managed Care & Healthcare Communications, LLC, disclaims responsibility for any injury to persons or property resulting from any ideas or products referred to in the articles or advertisements.

The contents of this supplement may include information regarding the use of products that may be inconsistent with or outside the approved labeling for these products in the United States. Physicians should note that the use of these products outside current approved labeling is considered experimental and are advised to consult prescribing information for these products.

THE AMERICAN JOURNAL OF MANAGED CARE® Supplement VOL. 25, NO. 8 S129


TABLE OF CONTENTS

Participating Faculty S130

Reports

Assessing the Burden of Illness of Chronic Hepatitis C and Impact of Direct-Acting Antiviral Use on Healthcare Costs in Medicaid S131

M. Christopher Roebuck, PhD; and Joshua N. Liberman, PhD

Appendix S140

A Supplement to The American Journal of Managed Care® PROJ A897

OVERVIEW

This supplement to The American Journal of Managed Care® analyzes the burden of illness of chronic hepatitis C virus infection in nonelderly adult Medicaid patients to esti-mate the impact of interferon-free direct-acting antiviral treatment on healthcare costs in Medicaid.

June 2019

Vol. 25 • No. 8, Sup.

S U P P L E M E N TTHE AMERICAN JOURNAL OF MANAGED CARE®

®

S130 JUNE 2019 www.ajmc.com

F A C U L T Y &DISCLOSURE

EDITORIAL & PRODUCTION

Senior Vice PresidentJeff Prescott, PharmD, RPh

Scientific Director Darria Zangari, PharmD, BCPS, BCGP

Senior Clinical Project ManagersIda Delmendo Danielle Mroz, MA

Clinical Project ManagerTed Pigeon

Senior Manager, Clinical Writing ServicesAngelia Szwed

Project ManagerAndrea Szeszko

Assistant EditorsHayley Fahey Jill Pastor

Copy ChiefJennifer Potash

Medical and Scientific Quality Review EditorStacey Abels, PhD

Copy EditorsMaggie Shaw Rachelle Laliberte Paul Silverman

Creative Director, PublishingRay Pelesko

Senior Art DirectorMelissa Feinen

DesignerJulianne Costello

SALES & MARKETING

Director, Sales Gil Hernandez

National Account Managers Ben Baruch Robert Foti Megan Halsch Ryan O’Leary

OPERATIONS & FINANCE

Circulation DirectorJon Severn [email protected]

Vice President, FinanceLeah Babitz, CPA

Controller Katherine Wyckoff

CORPORATE

Chairman and CEOMike Hennessy, Sr

Vice Chairman Jack Lepping

PresidentMike Hennessy, Jr

Chief Operating Officer George Glatcz

Chief Financial Officer Neil Glasser, CPA/CFE

Executive Creative DirectorJeff Brown

Senior Vice President, OperationsTom Tolvé

Senior Vice President, ContentSilas Inman

Senior Vice President, Information Technology OfficerJohn Moricone

Vice President, Corporate Development and IntegrationDave Heckard

Vice President, Business IntelligenceChris Hennessy

Vice President, Digital MediaJung Kim

Vice President, Human Resources and AdministrationShari Lundenberg

Copyright © 2019 by Managed Care & Healthcare Communications, LLC

Signed disclosures are on file at the office of The American Journal of Managed Care®, Cranbury, New Jersey.

FACULTYM. Christopher Roebuck, PhDPresident and Chief Executive OfficerRxEconomics, LLCHunt Valley, Maryland

Joshua N. Liberman, PhDSenior EpidemiologistRxEconomics, LLCHunt Valley, Maryland

FACULTY DISCLOSURESThese faculty have disclosed the following relevant commercial financial relationships or affiliations in the past 12 months.

M. Christopher Roebuck, PhD

OWNER RxEconomics, LLC

FUNDING RECEIVEDPharmaceutical Research and Manufacturers of America

Joshua N. Liberman, PhD, reports no potential conflicts of interest.


M ore than 2 million people are currently infected

with the hepatitis C virus (HCV) in the United

States.1 For many, an HCV infection is an asymp-

tomatic condition that often goes undiagnosed.

If untreated, the virus increases an individual’s risk of life-

threatening conditions such as cirrhosis, hepatocellular carcinoma,

and liver failure.2 As such, HCV imposes substantial costs on society.

Patients who are infected with HCV have poorer quality of life and

decreased productivity,3-5 consume more health services,6-11 and

have higher mortality rates.12 Moreover, healthcare needs increase

dramatically as HCV disease progresses.7,13-16

Until 2011, the primary treatment for chronic HCV infection

was a combination of pegylated interferon and ribavirin. With this

regimen, about 50% of patients were able to achieve “cure,” defined

by a sustained virologic response (SVR)—no measurable virus in the

blood—12 or 24 weeks after the end of treatment.17,18 The duration

of treatment was long (up to 48 weeks) and associated with high

discontinuation rates.19 In May 2011, the FDA approved the first agent

in a new therapeutic class known as direct-acting antivirals (DAAs).

Unlike peginterferon and ribavirin, DAAs interfere with the growth

and replication cycles of HCV itself.20 DAAs were initially used in

combination with peginterferon and ribavirin; however, since late 2013,

interferon-free DAA regimens have been available. Clinical evidence

indicates that these interferon-free DAA regimens are well tolerated

and effective, achieving SVR in 92% or more of patients, although

outcomes vary by genotype, prior treatment, and disease severity.21

DAAs were initially more expensive than older treatment options;

however, these costs have declined substantially over time with

increased competition. Indeed, within a year of the approval of the

first interferon-free regimen, additional interferon-free DAAs entered

the market, which enabled payers to negotiate large discounts and/

or rebates in exchange for favorable formulary placement. Largely

because of this increased competition, negotiated supplemental

rebates have risen from about 22% off list price in 2014 to as high

as 60% in ensuing years.22,23 Moreover, list prices for DAAs them-

selves have declined drastically, from nearly $100,000 per treatment

course in 2014 to as low as $24,000 per treatment course today.24

OBJECTIVES: To quantify the burden of illness of chronic hepatitis C virus (HCV) infection and estimate the impact of interferon-free direct-acting antiviral treatment on healthcare costs in Medicaid.

STUDY DESIGN: Observational, retrospective analysis.

METHODS: Medicaid claims data from 2012 for nonelderly adult enrollees with chronic HCV in 16 states were used to estimate the burden of HCV in Medicaid. Annual measures of health services utilization and cost for patients with HCV were compared with a control group of patients without HCV exactly matched on a robust set of individual characteristics and stratified according to liver disease severity, Medicaid eligibility group, and plan type. Subsequently, HCV burden-of-illness estimates were used in a separate analysis of Medicaid State Drug Utilization Data on interferon-free drug utilization and expenditures to estimate the annual and cumulative impact of these curative medications on national Medicaid costs from 2013 through 2022.

RESULTS: Annual per-person Medicaid healthcare costs attributed to HCV infection were estimated to range from $10,561 for noncirrhotic disabled adults to $46,263 for nondisabled adults with end-stage liver disease. The costs were due mainly to inpatient hospitalizations and outpatient hospital visits, prescription drug utilization, outpatient physician’s office/clinic visits, and laboratory tests. By 2014, the first full year following the approval of interferon-free treatment, an estimated 12,175 adults with HCV were cured in Medicaid nationwide, each avoiding an estimated $15,907 per year in healthcare costs associated with the disease. As more patients in Medicaid are treated and net savings continue to grow year after year—due to recurring avoidance of health services use and declining drug prices—total cumulative treatment costs since 2013 are expected to be fully offset by total cumulative healthcare expenditure reductions by the end of 2019. By 2022, the recurrent annual avoidance of healthcare costs will have delivered an estimated $12 billion in total cumulative savings to Medicaid, net of DAA drug expenditures.

CONCLUSIONS: The introduction of interferon-free HCV treatments enables the avoidance of significant healthcare costs previously associated with treating the disease year after year, producing annual cumulative Medicaid savings beginning in 2019. A main finding from this study is that the cost of a complete DAA treatment course, at 2018 estimated net prices, can be expected to be fully offset by healthcare cost savings after only 16 months, on average, on a per-person basis. Given the tremendous value provided by these curative drugs, Medicaid policies aimed toward restricting access to these treatments based on disease severity or other requirements would be shortsighted.

Am J Manag Care. 2019;25:S131-S139For author information and disclosures, see end of text.

R E P O R T

Assessing the Burden of Illness of Chronic Hepatitis C and Impact of Direct-Acting

Antiviral Use on Healthcare Costs in MedicaidM. Christopher Roebuck, PhD; and Joshua N. Liberman, PhD

ABSTRACT


R E P O R T

Despite a reduction in the costs of DAAs, state Medicaid programs

have expressed concerns over allowing universal access to these new

therapies because of the unique dual challenge of having both the

financial constraints of annual public budgets and high numbers of

HCV-infected enrollees.25 Consequently, many Medicaid programs

have chosen to restrict coverage of DAAs, based on parameters of

fibrosis stage (ie, degree of liver damage), abstinence from alcohol

and substance use, and prescriber type.26,27 From an economic effi-

ciency standpoint, the appropriateness of these access restrictions

depends not only on the costs of DAAs but also on the benefits

derived from their use.

Several economic evaluations of DAAs have been published.28-31

Moreover, burden-of-illness studies have been conducted on popu-

lations of patients with HCV in commercial insurance,7,10,13,14,32,33

Medicare,9 and the general US population.8,11 However, comparable

research in Medicaid is scant, with only 1 published study on a single

state’s experience.15 The present study estimates the healthcare costs

associated with chronic HCV infection in Medicaid using detailed

data from 16 states and more than 5 million Medicaid enrollees,

paired with actual interferon-free DAA utilization and expendi-

ture data to measure the annual and cumulative impact of these

curative medications on Medicaid costs from 2013 through 2022.

MethodsThis study was conducted in 2 separate stages using 2 distinct data

sources to estimate Medicaid costs attributable to HCV infection

and to Medicaid savings resulting from curative DAA treatment.

These sources were Medicaid Analytic eXtract (MAX) files, which

were used to quantify the per-patient cost burden of HCV infection,

and Medicaid State Drug Utilization Data (SDUD) files, which were

used to project the number of Medicaid beneficiaries cured of HCV

following the release of interferon-free DAAs and to simulate the

expected savings associated with these curative therapies.

Medicaid Analytic eXtract DataMAX files were obtained under a Data Use Agreement from CMS with

institutional review board (IRB) approval and oversight (Advarra

IRB; Columbia, MD). Created primarily to support research and

policy analysis, MAX data include pharmacy and medical claims

and encounter records, as well as eligibility information, on all

individuals enrolled in Medicaid.34,35 MAX files for the year 2012

from 16 states—Alabama, California, Connecticut, Florida, Illinois,

Indiana, Louisiana, Michigan, New Hampshire, New Mexico, New

York, Ohio, Oregon, Pennsylvania, Virginia, and Washington—

were utilized for this study. Participants were aged between 18 and

64 years as of December 31, 2012, with unrestricted Medicaid benefits

and without an annual gap in coverage of more than 30 days. After

these criteria were imposed, 5,210,249 adult Medicaid recipients

remained. Participants were then segmented according to their

Medicaid basis of eligibility: either adults who were blind/disabled

(hereafter “disabled”) or adults who were other nonblind/disabled

(hereafter “nondisabled”). They were further stratified by plan type:

either fee-for-service (FFS) or managed care (see Appendix Figure).

Medicaid State Drug Utilization DataThe SDUD files contain precise information on the counts and reim-

bursement amounts for all prescriptions dispensed in Medicaid

nationwide.36 Specifically, data were obtained on all interferon-

free DAA (hereafter just “DAA”) fills from the fourth quarter of 2013

through the second quarter of 2018. Package inserts for each DAA

product, which specify recommended dosage amounts and treat-

ment durations by cirrhosis status and treatment naïvety, were

used to determine the average number of prescriptions filled per

treated patient with HCV infection and were applied to the SDUD

to calculate the annual number of patients treated with DAAs.

Subsequently, expected DAA-specific SVR rates were used to deter-

mine the estimated annual number of patients cured of the virus,

accounting for treatment nonadherence. See Appendix for details.

HCV Burden-of-Illness AnalysisMAX claims and encounter data were analyzed to estimate Medicaid

costs attributable to an HCV diagnosis in 2012. Patients with chronic

HCV were identified using an algorithm employed by Gordon et al.14

Individuals were required to have at least 1 medical claim with a

diagnosis of chronic HCV; at least 2 medical claims on different

dates for unspecified HCV or HCV carrier; or 2 or more medical

claims at least 6 months apart for unspecified HCV, HCV carrier,

or acute HCV. Records for HCV testing were excluded from this

case-finding definition to avoid basing HCV status on rule-out

procedures. Using these criteria, a total of 72,109 individuals were

classified as having chronic HCV during the study period. Patients

were then assigned to 1 of 3 liver disease severity cohorts: noncir-

rhotic, cirrhosis, or end-stage liver disease (ESLD), based on the

work of Gordon et al.14 See the Appendix for details.

Patients with chronic HCV were exact-matched 1:1 to control

individuals (those without evidence of HCV) on the following demo-

graphic and plan characteristics: basis of eligibility, age, gender,

race, ethnicity, state of residence, plan type, any months enrolled

in primary care case management, and any months receiving cash

maintenance assistance. Individuals were also exact-matched on

the presence of diagnoses for asymptomatic HIV or symptomatic

HIV/AIDS because these often cooccur with, but are not caused by,

HCV infection. Because patients with HCV were exactly matched

to patients without HCV, no statistically significant differences

in mean values of any of the matching variables were present.

Additional details are provided in the Appendix.

Five count measures of annual health services utilization (HSU)

were constructed from the claims data: inpatient hospitalizations,


CHRONIC HEPATITIS C AND DIRECT-ACTING ANTIVIRAL USE IN MEDICAID

hospital days, emergency department (ED) visits, physician’s office/

clinic visits, and prescription drug fills (adjusted to 30-day equiva-

lents). For individuals enrolled in FFS plans, healthcare cost variables

were generated using the amounts paid by Medicaid. Cost measures

were not created for managed care plan enrollees because their health

services are routinely covered on a capitated basis. In the process of

building the MAX files, CMS classifies Medicaid expenditures into

33 specific types of service. For the present analysis, a subset of 14

of these were retained; the remaining 19, which contained little to

no spending, were summed to form an “other” category. Costs were

aggregated into drug and nondrug subtotals, as well as total health-

care costs. Because HCV prescription drug costs were expected to

be a significant part of the burden of illness in 2012, spending on

peginterferon and ribavirin—and the proportion of chronic HCV

patients treated with this regimen—was measured and reported

separately. The costs associated with the first 2 DAAs on the market

(boceprevir and telaprevir), which were used concomitantly with

peginterferon and ribavirin in 2012, were itemized.

Differences in mean values for the HSU and cost variables were

tested between the chronic HCV and control groups, as well as across

liver disease severity cohorts using the nonparametric Kruskal-

Wallis equality of populations test.37 All analyses were conducted

using Stata/MP version 15.1 (StataCorp LP; College Station, TX).

Impact of DAA Use on Healthcare Costs SimulationThe impact of DAA utilization on overall healthcare costs in Medicaid

from 2013 through 2022 was projected by combining the results

from the burden-of-illness analysis with DAA costs and utilization

data from the SDUD files.

Patients with HCV who were cured of the disease were expected

to have HSU similar to that of otherwise comparable individuals

without the infection. Specifically, it was assumed that 90% of the

estimated average burden of illness would be eliminated by the

cure. The remaining 10% of HCV costs would likely be more than

sufficient to cover the recommended posttreatment monitoring of

some individuals cured of the infection, which may include HCV

testing, ultrasound examination, and endoscopy.38 Patients were

classified as cured based on DAA product-specific expected SVR

rates, assuming a 90% medication adherence rate.39

The total cost of DAA treatment equaled total annual reimburse-

ments (derived from the SDUD) minus expected rebates. Estimated

rebates took into account the federally mandated Medicaid Drug

Rebate,40 any state-negotiated supplemental rebates, and compe-

tition from new products, which together produced a range of

23.1% to 59.5%. Total DAA expenditures (net of rebates) were

subtracted from total avoided healthcare costs due to curing of HCV

infection to yield the net financial impact of DAA use on Medicaid

costs, derived annually and cumulatively from 2013 through 2022.

Projected costs for the remainder of 2018 through 2022 assumed

that DAA prices and utilization rates will not change from the

levels exhibited in the first half of 2018. All costs were inflated to

2017 dollars using the Consumer Price Index for Medical Care41 (the

Appendix includes further details).

ResultsHCV Burden of IllnessBased on the sample selection process, the implied prevalence of

diagnosed chronic HCV infection was 1.4% among nonelderly adults

in Medicaid. This rate was substantially higher among disabled

enrollees (3.0%) relative to the cohort of nondisabled enrollees

(0.6%). In comparison with a recent estimate of HCV prevalence in

the entire adult US population of 1.0%, the present results reflect

a somewhat greater overall proportion of infected individuals in

Medicaid.1 Descriptive statistics for all variables employed in the

matching process are provided in Appendix Table A1. As reflected

in Tables 1 and 2, 71.6% of the disabled cohort and 86.8% of the

nondisabled cohort were classified as having noncirrhotic liver

disease. Furthermore, disabled patients with chronic HCV had

higher percentages of both cirrhosis (8.8% vs 4.8%) and ESLD

(19.6% vs 8.4%) than nondisabled patients with chronic HCV.

Among both eligibility groups, these percentages varied only slightly

between FFS and managed care Medicaid plans.

Regardless of insurance plan type, severity of liver disease, or

basis of Medicaid eligibility, individuals with chronic HCV infection

had significantly (P <.001) greater use of hospitals, physicians, EDs,

and prescription drugs (Tables 1 and 2). For example, patients with

chronic HCV averaged at least 1 additional hospitalization and 3 to

5 more inpatient hospital days annually compared with Medicaid

enrollees without the disease. Although HSU did not radically differ

between the noncirrhotic and cirrhotic cohorts, individuals with

ESLD had 2 to 3 times more hospitalizations and twice as many

ED visits compared with patients with less severe disease (see the

Appendix for more details).

Higher rates of HSU translated into significantly (P <.001) greater

healthcare costs (Table 3). Mean annual total costs were $53,159 per

disabled patient with chronic HCV and $35,280 for their controls

without the disease, for a difference of $17,879. Nearly two-thirds of

this difference was attributable to inpatient hospitalizations ($11,142).

Drug costs were greater by $5370, of which $1849 (34.4%) was for

boceprevir and telaprevir and $1237 (23.0%) was for peginterferon

and ribavirin, the older treatments supplanted by interferon-free

DAAs. Chronic HCV infection was also associated with higher costs

for physician visits ($1203), outpatient hospital visits ($1146), labo-

ratory and x-ray services ($810), clinic visits ($589), psychiatric

services ($365), and transportation services ($313). Across liver

disease severity cohorts, total healthcare costs were similar for

patients with noncirrhotic and cirrhotic disease; however, costs

were 69.6% higher for those with ESLD.


R E P O R T

TABLE 1. Health Services Utilization Means by Liver Disease Severity for Disabled Adults Cohort by Plan Type

Fee-for-Service

Noncirrhotic (n = 6899)

Cirrhosis (n = 978)

End-Stage Liver Disease

(n = 2248)

Total Chronic HCV (N = 10,125)

Control Group

(N = 10,125)

Variable Mean SD Mean SD Mean SD Mean SD Mean SD

Inpatient hospitalizations 1.4 3.4 1.2 3.8 3.0 4.8 1.7 3.9 0.5 1.7

Inpatient hospital days 5.9 31.7 4.0 28.9 12.0 44.1 7.1 34.7 2.5 24.0

Emergency department visits 3.1 6.2 3.0 5.7 5.7 8.7 3.7 6.9 1.7 3.8

Physician’s office/clinic visits 7.6 9.0 9.8 9.7 11.6 11.8 8.7 9.9 6.1 8.4

Prescription drug fills 73.2 53.0 76.5 50.7 86.7 58.4 76.5 54.3 67.7 58.4

Managed Care

Noncirrhotic (n = 29,983)

Cirrhosis (n = 3555)


(n = 7849)


Control Group

(N = 41,387)







HCV indicates hepatitis C virus.All differences in variable means across liver disease severity groups, and between total chronic HCV and control groups, are statistically significant (P <.001) using the Kruskal-Wallis equality of populations test.

TABLE 2. Health Services Utilization Means by Liver Disease Severity for Nondisabled Adults Cohort by Plan Type

Fee-for-Service


Cirrhosis (n = 231)


(n = 393)

Total Chronic HCV

(N = 4262)

Control Group

(N = 4262)







Managed Care

Noncirrhotic (n = 13,672)

Cirrhosis (n = 733)


(n = 1282)


Control Group

(N = 15,687)







HCV indicates hepatitis C virus.All differences in variable means across liver disease severity groups, and between total chronic HCV and control groups, are statistically significant (P <.001) using the Kruskal-Wallis equality of populations test.



The nondisabled cohort had lower cost levels than the disabled

cohort, but the incremental effect of chronic HCV was comparable

in magnitude and significance (P <.001). For example, mean total

healthcare costs were $26,788 for patients with chronic HCV versus

$9610 for the control group; this difference is $17,178, strikingly

similar to the $17,789 estimate derived for the disabled cohort

(Table 4). Inpatient services accounted for just over one-third

of this amount ($6263). Prescription drug spending was higher

by $6658, of which $3177 was for boceprevir and telaprevir and

$2265 was for the peginterferon and ribavirin treatment. Moreover,

expenditures were greater for psychiatric services ($1242), outpa-

tient hospital visits ($732), clinic visits ($726), laboratory and x-ray

services ($697), and physician visits ($437). Total healthcare costs

rose dramatically with liver disease severity, the most pronounced

increase being for inpatient costs.

Simulated Impact of DAA Use on Healthcare CostsThe results of an analysis of the impact of the use of DAAs on health-

care costs in Medicaid revealed that in 2014, the first complete year

following the release of interferon-free DAAs, 12,175 individuals

were estimated to have been cured of HCV (see Table 5). Treatment

rates increased over time, such that an estimated 157,519 individ-

uals had been cured by the end of 2018. By the end of 2022, 10 years

following the introduction of DAAs, we estimate that HCV will have

been eliminated in approximately 331,967 Medicaid enrollees. On

average, curing a patient with HCV saves an estimated $15,907 per

TABLE 3. Health Services Cost Means by MAX Type of Service by Liver Disease Severity for FFS Disabled Adults Cohort


Cirrhosis (n = 978)


(n = 2248)


Control Group

(N = 10,125)


Total healthcare costs $45,841 $94,704 $46,347 $59,390 $78,582 $115,073 $53,159 $97,851** $35,280 $63,108^^

Total drug costs $13,106 $44,931 $16,891 $41,455 $14,501 $58,171 $13,782 $47,893* $8412 $16,015^^

Peginterferon/ ribavirin costs

$1167 $4834 $2457 $7461 $918 $4666 $1237 $5128** $0 $0^^

Percentage treated with peginterferon/ribavirin

8.36% 27.69% 14.11% 34.83% 5.74% 23.26% 8.34% 27.64%** 0.00% 0.00%^^

Boceprevir, telaprevir costs

$1806 $9396 $3850 $13,487 $1113 $7074 $1849 $9451* $0 $0^^

Total nondrug costs $32,735 $72,711 $29,456 $44,255 $64,081 $93,213 $39,378 $76,777** $26,869 $59,336^^

Inpatient hospital $11,943 $34,778 $9430 $25,838 $33,668 $60,439 $16,524 $42,234** $5382 $20,421^^

Nursing facility services $6090 $25,234 $6829 $26,142 $9980 $28,655 $7025 $26,165** $7393 $29,204^

Outpatient hospital $2051 $7614 $2324 $5054 $3866 $8606 $2480 $7679** $1334 $5160^^

Physicians $1736 $20,034 $1618 $2291 $3939 $13,349 $2214 $17,731** $1011 $2919^^

Lab and x-ray $1452 $2789 $1916 $3412 $2654 $3915 $1764 $3174** $954 $3245^^

Clinic $1446 $4368 $1194 $2250 $1683 $5409 $1474 $4472* $885 $2929^^

Intermediate mental care facility

$1598 $46,062 $199 $6220 $949 $45,009 $1319 $43,579 $1998 $36,221

Psychiatric services $1227 $3605 $1026 $3104 $883 $2972 $1131 $3431** $766 $3174^^

Personal care services $842 $5864 $694 $3838 $1011 $5345 $865 $5586 $1072 $6737

Home health $800 $5631 $781 $4982 $968 $4809 $836 $5398** $914 $6302^

Durable medical equipment

$727 $3100 $787 $3259 $1061 $3157 $807 $3131** $712 $3052^^

Residential care $795 $10,728 $765 $9636 $280 $4922 $678 $9633 $1762 $16,471

Transportation services $467 $1755 $489 $2543 $958 $2199 $578 $1959** $265 $1070^^

Other $1562 $7712 $1403 $5783 $2179 $9943 $1684 $8109** $2420 $11,410^^

FFS indicates fee-for-service; HCV, hepatitis C virus; MAX, Medicaid Analytic eXtract files; peginterferon, pegylated interferon.All costs have been inflated to 2017 dollars using the Consumer Price Index for Medical Care (Bureau of Labor Statistics; bls.gov).Statistical significance of differences in variable means across liver disease severity groups, using the Kruskal-Wallis equality of populations test, are denoted as follows: **P <.001; *P <.01.Statistical significance of differences in variable means across total chronic HCV and control groups, using the Kruskal-Wallis equality of populations test, are denoted as follows: ^^P <.001; ^P <.01.


R E P O R T

year in healthcare costs associated with the disease (ie, an HCV

burden-of-illness estimate of $17,674 multiplied by the 90% assumed

reduction in disease-related spending). Importantly, these spending

reductions persist every year post cure. In aggregate, we estimate

that the total annual healthcare cost savings associated with alle-

viated HCV burden were $2.5 billion in 2018 and are expected to

reach $5.3 billion in 2022.

To calculate the net impact of DAA use on healthcare spending

in Medicaid, the costs of DAAs themselves were subtracted from

the estimated savings in reduced HCV burden. As previously

discussed, per-user DAA costs have steadily decreased since 2015

as multiple DAAs have entered the marketplace. For the Medicaid

program, total estimated annual postrebate DAA costs peaked in

2015 at $2.1 billion and declined to less than $1 billion in 2018. In

the years immediately following the approval of interferon-free

DAA regimens (2013-2016), annual DAA costs exceeded annual

savings from reduced HCV burden. However, in 2017 and beyond,

the annual healthcare cost offsets generated by curing HCV in

Medicaid patients eclipsed DAA costs. By 2018, the expected savings

in annual healthcare expenditures exceeded the costs of DAAs by

$1.5 billion, and this net impact is expected to reach more than

$4.3 billion by 2022.

Table 5 depicts the cumulative impact of DAAs since their debut

in 2013. Although accrued spending on DAAs was higher than the

savings from reduced HCV burden between 2013 and 2018, begin-

ning in 2019, Medicaid will have fully recouped all its investment

TABLE 4. Health Services Cost Means by MAX Type of Service by Liver Disease Severity for FFS Nondisabled Adults Cohort


Cirrhosis (n = 231)


(n = 393)

Total Chronic HCV

(N = 4262)

Control Group

(N = 4262)


Total healthcare costs $23,411 $32,943 $30,497 $39,887 $55,873 $117,719 $26,788 $48,740** $9610 $20,547^^

Total drug costs $9066 $19,286 $13,946 $24,776 $10,509 $18,672 $9463 $19,596** $2805 $7052^^

Peginterferon/ ribavirin costs

$2194 $6486 $3788 $8520 $2032 $6395 $2265 $6612 $0 $0^^

Percentage treated with peginterferon/ribavirin

14.18% 34.89% 22.51% 41.86% 11.96% 32.49% 14.43% 35.14% 0.00% 0.00%^^

Boceprevir, telaprevir costs

$3059 $12,103 $5067 $16,315 $3157 $11,113 $3177 $12,287 $0 $0^^

Total nondrug costs $14,345 $26,822 $16,551 $30,251 $45,365 $116,018 $17,325 $44,518** $6805 $18,197^^

Inpatient hospital $6114 $22,064 $7211 $24,034 $30,720 $112,049 $8442 $40,648** $2179 $12,666^^

Nursing facility services $446 $6485 $922 $10,978 $1935 $10,624 $609 $7278 $481 $7504

Outpatient hospital $1544 $4153 $1964 $3116 $3240 $5520 $1723 $4277** $991 $3432^^

Physicians $866 $2209 $1089 $1771 $2366 $2918 $1016 $2303** $579 $2514^^

Lab and x-ray $1183 $1515 $1623 $1781 $2404 $3042 $1319 $1764** $622 $1477^^

Clinic $1408 $2599 $1320 $2436 $1483 $3320 $1410 $2665 $684 $1878^^

Intermediate mental care facility

$0 $0 $0 $0 $0 $0 $0 $0 $0 $0

Psychiatric services $1794 $3173 $1636 $2714 $1419 $2429 $1751 $3089 $509 $1699^^

Personal care services $30 $851 $0 $0 $0 $0 $26 $787 $7 $235

Home health $71 $1277 $71 $459 $210 $919 $84 $1218* $51 $1195^

Durable medical equipment

$271 $1601 $220 $413 $747 $2581 $312 $1682** $195 $1273^^

Residential care $1 $33 $0 $0 $0 $0 $1 $30 $84 $4166

Transportation services $143 $604 $143 $374 $432 $956 $170 $641** $53 $278^^

Other $474 $1546 $353 $571 $408 $660 $461 $1449 $369 $1646^^

FFS indicates fee-for-service; HCV, hepatitis C virus; MAX, Medicaid Analytic eXtract files; peginterferon, pegylated interferon.All costs have been inflated to 2017 dollars using the Consumer Price Index for Medical Care (Bureau of Labor Statistics; bls.gov).Statistical significance of differences in variable means across liver disease severity groups, using the Kruskal-Wallis equality of populations test, are denoted as follows: **P <.001; *P <.01.Statistical significance of differences in variable means across total chronic HCV and control groups, using the Kruskal-Wallis equality of populations test, are denoted as follows: ^^P <.001; ^P <.01.



in these HCV cures. The cumulative impact of DAA use in Medicaid

due to total healthcare expenditure reductions, net of cumulative

DAA costs since 2013, is expected to grow from $1.1 billion at the

end of the 2019 to more than $12 billion after 2022—just a decade

after the debut of interferon-free DAAs. These financial savings will

have been generated through the estimated avoidance of 1.5 million

hospitalizations, 2.7 million ED visits, and 16.6 million prescrip-

tion drug fills. (See the Appendix for more details.)

DiscussionThe objectives of this study were to estimate the burden of HCV and

quantify the impact of DAA use on healthcare costs in Medicaid.

Few investigators have evaluated these specific topics using real-

world evidence. Medicaid claims and DAA utilization data were

employed to address this gap in the extant literature. Annual health-

care costs due to chronic HCV infection were estimated at $17,879

for the disabled cohort and $17,178 for the nondisabled cohort.

The burden of illness increased with liver disease severity, from

a low of $10,561 for noncirrhotic disabled individuals to a high of

$46,263 for nondisabled individuals with ESLD. Among the disabled

patients, inpatient hospitalizations accounted for nearly two-thirds

of the costs of chronic HCV, yet they accounted for only one-third

of the costs among nondisabled patients. Prescription drug costs

were also substantially higher for patients with chronic HCV, the

majority of which were attributed to older HCV treatment regimens.

In a privately insured cohort, McAdam-Marx et al13 estimated

the per-person per-year incremental impact of chronic HCV to be

$9681 in 2009 ($12,251 inflated to 2017 dollars).41 This estimate is

about 30% lower than the $17,178 and $17,789 figures reported herein.

Using the same underlying commercial claims database, Gordon

et al14 calculated the average annual total healthcare costs for a

patient with HCV to be $24,176 in 2010 ($30,595 in 2017 dollars),41

also about 30% lower than the blended (disabled and nondisabled

adults) average of $45,347 derived in the present analysis. Gordon

et al also concluded that individuals with HCV and cirrhosis had

total healthcare costs that were about 30% greater than those of

patients with HCV who were noncirrhotic, and those with ESLD

had expenditures that were 2.6 times that of cirrhotic patients.14

TABLE 5. Impact of DAA Use on Healthcare Costs in Medicaid, 2013-2022a

YEAR

2013 ACT

2014 ACT

2015 ACT

2016 ACT

2017 ACT

2018 EST

2019 EST

2020 EST

2021 EST

2022 EST

DAA treatment costs

Total amount reimbursed for DAAs ($M)

$4 $1505 $3021 $3666 $3149 $2001 $2001 $2001 $2001 $2001

Estimated average rebate rate 23.1% 23.1% 31.0% 59.5% 54.1% 50.6% 53.3% 53.3% 53.3% 53.3%

Estimated total net cost of DAAs ($M)

$3 $1157 $2084 $1485 $1445 $988 $934 $934 $934 $934

HCV healthcare cost savings

Estimated number of patients cured

32 12,175 26,199 35,157 40,344 43,612 43,612 43,612 43,612 43,612

Estimated cumulative number of patients cured

32 12,207 38,406 73,563 113,907 157,519 201,131 244,743 288,355 331,967

Burden of illness of HCV ($PPPY) $15,808 $16,186 $16,612 $17,241 $17,674 $17,674 $17,674 $17,674 $17,674 $17,674

Estimated percentage of burden saved if cured

90% 90% 90% 90% 90% 90% 90% 90% 90% 90%

Estimated healthcare cost savings ($PPPY)

$14,227 $14,567 $14,951 $15,517 $15,907 $15,907 $15,907 $15,907 $15,907 $15,907

Estimated total healthcare cost savings ($M)

$0.5 $178 $574 $1141 $1812 $2506 $3199 $3893 $4587 $5280

Net total healthcare cost savings from DAA use ($M, nominal)

–$3 –$979 –$1510 –$344 $367 $1517 $2265 $2959 $3653 $4346

Net total healthcare cost savings from DAA use ($M, 2017)

–$3 –$1070 –$1606 –$352 $367 $1517 $2265 $2959 $3653 $4346

Cumulative net total healthcare cost savings from DAA use ($M, 2017)

–$3 –$1072 –$2679 –$3031 –$2664 –$1147 $1118 $4077 $7729 $12,076

ACT indicates actual; DAA, direct-acting antiviral; EST, estimated; HCV, hepatitis C virus; M, millions; PPPY, per patient per year.aActual values from quarters 1 and 2 of 2018 used to forecast values for remainder of 2018 through 2022.


R E P O R T

Considered alongside these 2 published studies, the current find-

ings suggest that the burden of illness of chronic HCV may be

greater among patients with Medicaid compared with those with

employer-sponsored or other commercial health insurance.

With both higher per-patient HCV burden and higher HCV

prevalence rates, Medicaid program directors should be keenly

interested in understanding the financial impact of DAA use. The

cure rates offered by highly effective DAAs present the rare oppor-

tunity to substantially and permanently reduce overall healthcare

costs. Findings from this study indicate that the cost of DAA treat-

ment, at 2018 estimated net prices, can be expected to be fully

offset by healthcare cost savings after only 16 months, on average,

on a per-person basis. These savings are realized in several ways.

First, patients who are cured of HCV require less medical care. The

current results demonstrate that individuals who are HCV-free have

fewer hospitalizations, ED visits, laboratory tests, and physician

encounters. Importantly, these reductions in HSU and costs are

not onetime events but instead occur annually for individuals who

are HCV-free. Second, prior to the introduction of DAAs, the most

common treatment for HCV infection involved interferon, which

is associated with significant costs and harmful adverse effects.

The morbidity issues and financial expenditures associated with

older ineffective regimens can be avoided entirely. Third, costs for

patients with HCV who are treated with DAAs are declining over

time because of increased competition within the therapeutic

class, which has led to estimated rebates as high as 60%.22-24 This

competitive landscape has also resulted in a decline in list prices,

which have fallen by more than 70% since the launch of the first

interferon-free DAAs.22-24

A key finding of this study is that, since 2017, annual Medicaid

healthcare savings for patients cured of HCV have exceeded DAA

treatment costs. We estimate annual savings of $1.5 billion resulting

from curative treatment; that figure is expected to grow to more

than $4.3 billion in 2022. Thus, on a cumulative basis, Medicaid

will have fully recouped all its investment in these HCV cures by

mid-2019 with cumulative savings of $1.1 billion, growing to more

than $12 billion after 2022, just a decade after the debut of inter-

feron-free HCV drugs. Improvements in patient quality of life and

enhanced productivity can also be expected to accompany these

healthcare cost savings.

LimitationsThis study is not without limitations. First, despite the large sample

size, Medicaid claims data used to estimate burden of HCV on

all 50 states were not received. Therefore, results might not be

generalizable to the entire adult Medicaid population. Second, the

control group was constructed by matching on demographic and

plan characteristics, as well as on HIV/AIDS status; positive HIV/

AIDS status is a high-cost comorbidity that is not caused by, but is

otherwise correlated with, HCV infection. The omission of control

variables for other conditions could give rise to biased estimates if

they are correlated with HCV, but inclusion of them could also lead

to bias if they are causally linked to HCV.42 For example, injection

drug use—one cause of infection—may persist post HCV cure. In

such cases, the HSU and costs associated with injection drug use

would not be averted by DAAs. Without a reliable claims-based

algorithm for identifying persons who inject drugs, this potential

confounding remains a limitation of the present study. Third, the

construction of chronic HCV and liver severity cohorts was based

on diagnosis and procedure codes from claims data and encounter

records. Although this case-finding definition was highly detailed

and had been published previously,14 the possibility for misclassi-

fication remains. More recent work by Gordon et al43 demonstrates

the limitations of relying on claims data alone to define levels of

liver disease severity. It is also worth noting that since HCV infection

often goes undiagnosed, the control group may contain individuals

who are infected with HCV, which would result in downward-biased

burden-of-illness estimates.

Additionally, the projected savings to Medicaid are calculated

based on DAA spending and utilization from 2013 to 2018; however,

the burden of illness of HCV, used to approximate cost savings

following cure, is estimated using 2012 claims data. It is possible

that patterns of healthcare spending and utilization have evolved

since 2012. Similarly, the distribution of liver disease severity

among individuals infected with HCV may be changing over time,

particularly since interferon-free DAAs were initially focused on

patients with cirrhosis. Finally, although the impact of DAA use

was assessed from the perspective of Medicaid, it is possible, or

even probable, that much of the healthcare cost savings resulting

from DAAs may be enjoyed by other payers—most notably Medicare,

because of the aging of the population infected with HCV.

ConclusionsGiven the considerable burden of HCV in Medicaid and the tremen-

dous value delivered by DAAs, Medicaid policies that restrict

access to them—such as requirements for liver biopsy, advanced

disease stage, sobriety, and specialist prescribers—would seem

to be shortsighted. Although many barriers to treatment remain,

positive efforts to improve access are under way. A 2017 report on

the status of access to DAAs in Medicaid found that many states

have decreased restrictions based on severity of liver damage, and

fewer states require prescriptions by specialists relative to policies

in place in 2014. However, the report also found that more states

have implemented sobriety requirements.27 In recognition of the

findings presented herein, the elimination of access restrictions on

interferon-free DAAs for patients with HCV would not only drive

down prevalence of the disease and associated healthcare costs but

also produce substantial savings for state Medicaid programs. n



Author Affiliations: RxEconomics, LLC

Funding Source: Financial support for this work was provided by the Pharmaceutical Research and Manufacturers of America (PhRMA).

Author Disclosure: Dr Roebuck is owner of RxEconomics, LLC, a health economics consultancy, which received funding from PhRMA for this study. Dr Liberman reports no potential conflicts of interest.

Authorship Information: Concept and design (MCR); Acquisition of data (MCR); Analysis and interpretation of data (MCR, JNL); Drafting of manu-script (MCR, JNL); Critical revision of manuscript for important intellectual content (MCR, JNL); Statistical analysis (MCR); Obtaining funding (MCR); Administrative, technical, or logistical support (MCR); and Supervision (MCR).

Address correspondence to: M. Christopher Roebuck, PhD, President & CEO; RxEconomics, LLC, 11350 McCormick Rd, EPII Ste 705; Hunt Valley, MD 21031. Email: [email protected].

REFERENCES1. Hofmeister MG, Rosenthal EM, Barker LK, et al. Estimating prevalence of hepatitis C virus infection in the United States, 2013-2016. Hepatology. 2019;69(3):1020-1031. doi: 10.1002/hep.30297.2. Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci. 2006;3(2):47-52.3. Su J, Brook RA, Kleinman NL, Corey-Lisle P. The impact of hepatitis C virus infection on work absence, productivity, and healthcare benefit costs. Hepatology. 2010;52(2):436-442. doi: 10.1002/hep.23726.4. Stepanova M, Kanwal F, El-Serag HB, Younossi ZM. Insurance status and treatment candidacy of hepa-titis C patients: analysis of population-based data from the United States. Hepatology. 2011;53(3):737-745. doi: 10.1002/hep.24131.5. Pascual-Argente N, Puig-Junoy J, Llagostera-Punzano A. Non-healthcare costs of hepatitis C: a sys-tematic review. Expert Rev Gastroenterol Hepatol. 2018;12(1):19-30. doi: 10.1080/17474124.2017.1373016.6. Xu F, Tong X, Leidner AJ. Hospitalizations and costs associated with hepatitis C and advanced liver disease continue to increase. Health Aff (Millwood). 2014;33(10):1728-1735. doi: 10.1377/hlthaff.2014.0096.35.7. Davis KL, Mitra D, Medjedovic J, Beam C, Rustgi V. Direct economic burden of chronic hepatitis C virus in a United States managed care population. J Clin Gastroenterol. 2011;45(2):e17-e24. doi: 10.1097/MCG.0b013e3181e12c09.8. Galbraith JW, Donnelly JP, Franco RA, Overton ET, Rodgers JB, Wang HE. National estimates of healthcare utilization by individuals with hepatitis C virus infection in the United States. Clin Infect Dis. 2014;59(6):755-764. doi: 10.1093/cid/ciu427.9. Rein DB, Borton J, Liffmann DK, Wittenborn JS. The burden of hepatitis C to the United States Medicare system in 2009: descriptive and economic characteristics. Hepatology. 2016;63(4):1135-1144. doi: 10.1002/hep.28430.10. Teshale EH, Xing J, Moorman A, et al; CHeCS Investigators. Higher all-cause hospitalization among patients with chronic hepatitis C: the Chronic Hepatitis Cohort Study (CHeCS), 2006-2013. J Viral Hepat. 2016;23(10):748-754. doi: 10.1111/jvh.12548.11. Stepanova M, De Avila L, Afendy M, et al. Direct and indirect economic burden of chronic liver disease in the United States. Clin Gastroenterol Hepatol. 2017;15(5):759-766.e5. doi: 10.1016/j.cgh.2016.07.020.12. Innes H, McAuley A, Alavi M, Valerio H, Goldberg D, Hutchinson SJ. The contribution of health risk behaviors to excess mortality in American adults with chronic hepatitis C: a population cohort-study. Hepatology. 2018;67(1):97-107. doi: 10.1002/hep.29419.13. McAdam-Marx C, McGarry LJ, Hane CA, Biskupiak J, Deniz B, Brixner DI. All-cause and incremental per patient per year cost associated with chronic hepatitis C virus and associated liver complications in the United States: a managed care perspective. J Manag Care Pharm. 2011;17(7):531-546. doi: 10.18553/jmcp.2011.17.7.531.14. Gordon SC, Pockros PJ, Terrault NA, et al. Impact of disease severity on healthcare costs in patients with chronic hepatitis C (CHC) virus infection. Hepatology. 2012;56(5):1651-1660. doi: 10.1002/hep.25842.15. Menzin J, White LA, Nichols C, Deniz B. The economic burden of advanced liver disease among patients with hepatitis C virus: a large state Medicaid perspective. BMC Health Serv Res. 2012;12:459. doi: 10.1186/1472-6963-12-459.16. Razavi H, Elkhoury AC, Elbasha E, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology. 2013;57(6):2164-2170. doi: 10.1002/hep.26218.17. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358(9286):958-965.18. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347(13):975-982. doi: 10.1056/NEJMoa020047.

19. Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med. 2006;355(23):2444-2451. doi: 10.1056/NEJMct061675.20. Rosen HR. Clinical practice. Chronic hepatitis C infection. N Engl J Med. 2011;364(25):2429-2438. doi: 10.1056/NEJMcp1006613.21. Falade-Nwulia O, Suarez-Cuervo C, Nelson DR, Fried NW, Segal JB, Sulkowski MS. Oral direct-acting agent therapy for hepatitis C virus infection: a systematic review. Ann Intern Med. 2017;166(9):637-648. doi: 10.7326/M16-2575.22. Silverman E. The hepatitis C scorecard: Gilead is trouncing AbbVie, but at a price. The Wall Street Journal. February 12, 2015. blogs.wsj.com/pharmalot/2015/02/12/the-hepatitis-c-scorecard-gilead-is-trouncing-abbvie-but-at-a-price/. Accessed January 30, 2019.23. Fein AJ. What Gilead’s big Hepatitis C discounts mean for biosimilar pricing. Drug Channels website. drugchannels.net/2015/02/what-gileads-big-hepatitis-c-discounts.html. Published February 5, 2015. Accessed June 1, 2019.24. Loftus P. Merck to limit drug price increases. The Wall Street Journal. July 19, 2018. wsj.com/articles/merck-to-limit-drug-price-increases-cut-some-prices-1532037433. Accessed June 1, 2019.25. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. 1999;341(8):556-562. doi: 10.1056/NEJM199908193410802.26. Barua S, Greenwald R, Grebely J, Dore GJ, Swan T, Taylor LE. Restrictions for Medicaid reimburse-ment of sofosbuvir for the treatment of hepatitis C infection in the United States. Ann Intern Med. 2015;163(3):215-223. doi: 10.7326/M15-0406.27. National Viral Hepatitis Roundtable and Center for Health Law and Policy Innovation, Harvard Law School. Hepatitis C: the state of Medicaid access–2017 national summary report. Center for Health Law and Policy Innovation website. chlpi.org/wp-content/uploads/2013/12/State-of-HepC_2017_FINAL.pdf. Published October 23, 2107. Accessed January 30, 2018.28. Leidner AJ, Chesson HW, Xu F, Ward JW, Spradling PR, Holmberg SD. Cost-effectiveness of hepatitis C treatment for patients in early stages of liver disease. Hepatology. 2015;61(6):1860-1869. doi: 10.1002/hep.27736.29. Najafzadeh M, Andersson K, Shrank WH, et al. Cost-effectiveness of novel regimens for the treatment of hepatitis C virus. Ann Intern Med. 2015;162(6):407-419. doi: 10.7326/M14-1152.30. Wittenborn J, Brady J, Dougherty M, Rein D. Potential epidemiologic, economic, and budgetary impacts of current rates of hepatitis C treatment in Medicare and non-Medicare populations. Hepatol Commun. 2017;1(2):99-109. doi: 10.1002/hep4.1031.31. Younossi Z, Gordon SC, Ahmed A, Dieterich D, Saab S, Beckerman R. Treating Medicaid patients with hepatitis C: clinical and economic impact. Am J Manag Care. 2017;23(2):107-112.32. Gordon SC, Hamzeh FM, Pockros PJ, et al. Hepatitis C virus therapy is associated with lower health care costs not only in noncirrhotic patients but also in patients with end-stage liver disease. Aliment Pharmacol Ther. 2013;38(7):784-793. doi: 10.1111/apt.12454.33. Goolsby HA, Rosenblatt L, Patel C, Blauer-Peterson C, Anduze-Faris B. Clinical characteris-tics, healthcare costs, and resource utilization in hepatitis C vary by genotype. Curr Med Res Opin. 2017;33(5):829-836. doi: 10.1080/03007995.2017.1288613.34. Medicaid Analytic eXtract general information. CMS website. cms.gov/Research-Statistics-Data-and-Systems/Computer-Data-and-Systems/MedicaidDataSourcesGenInfo/MAXGeneralInformation.html. Accessed May 1, 2019.35. Medicaid Analytic eXtract Files (MAX) user guide, version 2.2. Chronic Condition Data Warehouse/CMS website. ccwdata.org/documents/10280/19002246/ccw-max-user-guide.pdf. Published January 2019. Accessed May 1, 2019.36. State drug utilization data. Medicaid website. medicaid.gov/medicaid/prescription-drugs/state-drug-utilization-data/index.html. Accessed December 3, 2018. 37. Kruskal WH, Wallis WA. Use of ranks in one-criterion variance analysis. J Am Stat Assoc. 1952;47:583-621. doi: 10.2307/2280779.38. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Monitoring patients who are starting HCV treatment, are on treatment, or have completed therapy. HCV Guidelines website. hcvguidelines.org/evaluate/monitoring. Updated May 24, 2018. Accessed April 12, 2019.39. Younossi ZM, Stepanova M, Henry L, Nader F, Younossi Y, Hunt S. Adherence to treatment of chronic hepatitis C: from interferon containing regimens to interferon and ribavirin free regimens. Medicine (Baltimore). 2016;95(28):e4151. doi: 10.1097/MD.0000000000004151.40. Medicaid drug rebate program. Medicaid website. medicaid.gov/medicaid/prescription-drugs/ medicaid-drug-rebate-program/index.html. Updated November 13, 2018. Accessed December 3, 2018.41. Consumer Price Index. Bureau of Labor Statistics website. bls.gov/cpi/. Accessed May 1, 2019.42. Lee DW, Meyer JW, Clouse J. Implications of controlling for comorbid conditions in cost-of-illness estimates: a case study of osteoarthritis from a managed care system perspective. Value Health. 2001;4(4):329-334.43. Gordon SC, Lamerato LE, Rupp LB, et al. Prevalence of cirrhosis in hepatitis C patients in the Chronic Hepatitis Cohort Study (CHeCS): a retrospective and prospective observational study. Am J Gastroenterol. 2015;110(8):1169-1177; quiz 1178. doi: 10.1038/ajg.2015.203.


MethodsIdentification and Selection of Study ParticipantsThe Appendix Figure1,2 shows the sample selection process for

the burden-of-illness component of the analysis. Claims and

encounter data were analyzed to identify patients with chronic

hepatitis C virus (HCV) infection using the algorithm employed by

Gordon et al.2 To be deemed eligible, an individual was required to

have at least 1 claim with an International Classification of Diseases,

9th Revision, Clinical Modification (ICD-9-CM) diagnosis code for

chronic HCV (070.44; 070.54); at least 2 claims on different dates

for unspecified HCV (070.70; 070.71) or HCV carrier (V02.62); or 2

or more claims at least 6 months apart for unspecified HCV, HCV

carrier, or acute HCV (070.41; 070.51). All claims with Current

Procedural Terminology codes for HCV testing (86803, 86804,

87520, 87521, 87522) were excluded from this case-finding defini-

tion to avoid basing HCV status on procedures ordered to rule out

infection only. Using these criteria, 72,109 individuals were clas-

sified as having chronic HCV. Based also on the work of Gordon et

al,2 patients were assigned to 1 of 3 liver disease severity cohorts

using diagnosis and procedure codes: noncirrhotic, cirrhosis, or

end-stage liver disease (ESLD). The coding detail utilized is avail-

able in Gordon et al.2

Patients with chronic HCV were exact-matched (1:1) to control

individuals (those without evidence of HCV) on the following

demographic, plan, and clinical characteristics: Medicaid basis of

eligibility (disabled, nondisabled); age (coarsened in 16 three-year

bands); gender (male, female); race (white, black, other); ethnicity

(Hispanic, non-Hispanic); state of residence; Medicaid plan type

(fee-for-service [FFS], managed care); any enrollment (yes, no) in

primary care case management; any receipt (yes, no) of cash main-

tenance assistance; and diagnosis of asymptomatic HIV (ICD-9-CM

code V08) or symptomatic HIV/AIDS (ICD-9-CM codes 042, 795.71)

because these often cooccur with, but are not caused by, HCV infec-

tion. Because participants with HCV and those without were exactly

matched to each other (as opposed to propensity score matched),

no statistically significant differences in mean values of any of the

matching variables were present.

Burden of Illness AnalysisFive count measures of annual health services utilization (HSU)

were constructed: inpatient hospitalizations, hospital days,

emergency department (ED) visits, physician’s office/clinic visits,

and prescription drug fills (adjusted to 30-day equivalents). For

individuals enrolled in FFS plans, healthcare cost variables were

generated using the amounts paid by Medicaid. Cost measures

were not created for managed care plan enrollees because their

health services are routinely paid for on a capitated basis. In the

process of building the Medicaid Analytic eXtract (MAX) files, CMS

classifies Medicaid expenditures into 33 specific types of service.

For the present analysis, a subset of 14 of these was retained; the

remaining 19, which contained little to no spending, were summed

to form an “other” category. Costs were aggregated into drug and

nondrug subtotals, as well as total healthcare costs. Specific drug

utilization and costs associated with peginterferon and ribavirin,

and the proportion of chronic HCV patients treated with this

regimen, were also captured. Also itemized were the treatment

costs associated with the first 2 direct-acting antivirals (DAAs) on

the market—Victrelis (boceprevir) and Incivek/Incivo (telaprevir)—

that were used concomitantly with peginterferon and ribavirin and

were available during 2012.

Differences in mean values for the HSU and cost variables

were tested between the chronic HCV and control groups, as well

as across liver disease severity cohorts using the nonparametric

Kruskal-Wallis equality of populations test.3

Impact of DAA Use on Healthcare Costs AnalysisDAA Characteristics and Model Assumptions

An assessment of the impact of DAA utilization on healthcare costs

in Medicaid was conducted for the 10-year period 2013 through 2022.

We first generated a list of all DAAs that are indicated for HCV treat-

ment but that do not require concomitant use of interferon. The

following were included: Sovaldi (sofosbuvir), Harvoni (ledipasvir/

sofosbuvir), Viekira Pak (ombitasvir/paritaprevir/ritonavir with

dasabuvir), Technivie (ombitasvir/paritaprevir/ritonavir), Zepatier

(elbasvir/grazoprevir), Epclusa (sofosbuvir/velpatasvir), Viekira XR

A P P E N D I X

Assessing the Burden of Illness of Chronic Hepatitis C and Impact of Direct-Acting

Antiviral Use on Healthcare Costs in MedicaidM. Christopher Roebuck, PhD; and Joshua N. Liberman, PhD



(dasabuvir/ombitasvir/paritaprevir/ritonavir), Vosevi (sofosbuvir/

velpatasvir/voxilaprevir), and Mavyret (glecaprevir/pibrentasvir).

Daklinza (daclatasvir)—an adjunct therapy—was excluded from this

analysis, as was ribavirin. The first interferon-free DAA (Sovaldi)

was released in December 2013, and the most recent agent (Mavyret)

entered the market in August 2017. In January 2019, generic versions

of Harvoni and Epclusa were released.

From product package inserts, we gleaned DAA-specific recom-

mended treatment durations, which can vary according to virus

genotype, cirrhosis status, and prior HCV pharmacotherapy status.

Using this information, we calculated the average number of prescrip-

tions required per treated HCV patient. For all DAAs, 4 treatment

weeks equated to 1 prescription. The assumed compensated cirrhosis

rate was 24%, as measured in the burden-of-illness component

of our analysis. We also assumed 90% of patients with HCV were

naïve to medication for HCV, which is approximately 100% minus

the HCV treatment prevalence rate observed in our Medicaid data.

Furthermore, our analysis does not accommodate HCV reinfection

because that is not likely a direct effect of DAA utilization itself. In 2

studies involving interferon-free DAAs, measured compliance rates

were 84% and 96%; therefore, we adopted the midpoint (90%) as the

DAA adherence rate.4 Our assumption that 10% of DAA utilization is

essentially wasted, however, is likely conservative because the rela-

tionship between nonadherence and sustained virologic response

(SVR) is not yet clear.5 Finally, expected DAA-specific SVR rates were

drawn from the packet inserts, which include published phase 3

randomized clinical trial results. Values for the model assumptions

described in this paragraph are presented in the Appendix Table A1.

DAA Utilization and Estimation of Number Cured

The next step in this analysis was to estimate the number of patients

with chronic HCV cured by interferon-free DAAs. For each calendar

APPENDIX FIGURE. Sample Selection Process1,2

aAs reported in Mathematica Policy Research.1

bThese exclusions were applied prior to receiving the data from CMS. Therefore, they cannot be split into discrete steps.cUsing claims-based algorithm described in Gordon et al 2012.2

dMatched within basis of eligibility/plan type cohort on age, gender, race, ethnicity, selected Medicaid plan characteristics, and HIV/AIDS status.

Individuals with HCV matched 1:1 with non-HCV controlsd

Classified individuals with chronic hepatitis C virus (HCV) infectionc

Segmented according to Medicaid plan type

Excluded individuals with restricted benefits, >30-day coverage gap, any private health insurance or Medicare eligibility; and those residing in long-term care facilitiesb

Subset of 16 states: AL, CA, CT, FL, IL, IN, LA, MI, NH, NM, NY, OH, OR, PA, VA, and WAa

Excluded elderly adults (aged ≥65 years) and children (aged <18 years) and stratified by basis of eligibility groupsa

All 2012 Medicaid recipients (except CO, ID, KS, RI)a

All MedicaidN = 71,701,046

Disabled AdultsN = 10,987,509

N = 6,126,761

N = 1,752,137

Managed CareN = 1,381,964

N = 41,479

N = 41,387

Fee-for-Service N = 370,173

N = 10,490

N = 10,125

Nondisabled AdultsN = 20,266,486

N = 13,459,195

N = 3,458,112

Managed Care N = 2,752,261

N = 15,779

N = 15,687

Fee-for-ServiceN = 705,851

N = 4361

N = 4262


A P P E N D I X

quarter (Q) from Q4/2013 through Q2/2018 for both FFS and managed

care plans, separately, we extracted from the Medicaid State Drug

Utilization Data (SDUD) the number of prescriptions dispensed for

the DAAs using all associated National Drug Codes.6 For each DAA,

we subsequently divided the total number of fills by the estimated

average number of prescriptions required per treated patient with

HCV and then multiplied by the expected SVR rate to yield the

estimated number of people cured by each drug (see Appendix

Tables A2 through A7).

DAA Reimbursement Amounts and Rebate Assumptions

In addition to counts of prescriptions dispensed, SDUD files also

include actual reimbursement amounts paid by Medicaid for those

medications. These reported costs, however, do not consider rebates

received, neither via private negotiation between Medicaid and

manufacturers nor those required by law under the Medicare Drug

Rebate Program (MDRP).7 Although complete rebate data are not

publicly available, the MDRP rate of 23.1% of average manufacturer

price for branded drugs (13% for generics) is the minimum that

the Medicaid program would have received for the DAAs under

study. We assumed the average rebate would also be sensitive to

the competitive landscape in each year. For example, in 2013 and

2014, only 1 manufacturer had interferon-free DAAs on the market.

Thus, it is reasonable to assume that the statutory rebate of 23.1%

prevailed during that time. In successive years when new DAAs

emerged, we assumed that all drugs were sufficiently discounted

(via increased rebates) to match the lowest DAA price minus the

appropriate MDRP. These year-specific rebate assumptions and

brief rationales are reported in Appendix Tables A2 through A7.

Healthcare Cost Savings from DAA Use

For each year, we summed the actual reimbursement amounts for

all DAAs dispensed and subtracted the assumed rebates to yield the

estimated total net spending on DAA treatment (Appendix Table A8).

APPENDIX TABLE A1. DAAs Characteristics and Model Assumptions

DrugApproval

Date Treatment Duration Recommendations

Average Number of Rxs per Treated Patient, Accounting for Nonadherence

Expected SVR Rate

Sofosbuvir Dec 2013 12 or 24 weeks depending on virus genotype 4.13 92%

Ledipasvir/sofosbuvir Oct 201412 weeks without compensated cirrhosis

4.13 94%24 weeks with compensated cirrhosis

Ombitasvir/paritaprevir/ritonavir with dasabuvir

Dec 201412 weeks without compensated cirrhosis


Ombitasvir/paritaprevir/ritonavir Jul 2015 12 weeks 3.33 99%

Elbasvir/grazoprevir Jan 2016 12 weeks 3.33 95%

Sofosbuvir/velpatasvir Jun 2016 12 weeks with or without compensated cirrhosis 3.33 94%

Dasabuvir/ombitasvir/ paritaprevir/ritonavir

Jul 201612 weeks without compensated cirrhosis


Sofosbuvir/velpatasvir/voxilaprevir Jul 2017 12 weeks 3.33 95%

Glecaprevir/pibrentasvir Aug 2017

8 weeks for treatment naïve without compensated cirrhosis

2.59 99%

12 weeks for treatment naïve with compensated cirrhosis

8-16 weeks for previously treated without compensated cirrhosis

12-16 weeks for previously treated with compensated cirrhosis

Compensated cirrhosis rate 24%

Treatment-naïve rate 90%

DAA adherence rate 90%

DAA indicates direct-acting antiviral (interferon-free); Rx, prescription; SVR, sustained virological response.For all DAAs, 4 treatment weeks equate to 1 Rx.Some DAAs may have been used with ribavirin or daclatasvir (these drugs were not included as independent agents).

CONTINUED ON S150 ›



APPENDIX TABLE A2. DAA Drug Utilization and Cost in Medicaid, 2013

NDC Drug Name Plan Type Quarter Number of Prescriptions Medicaid Amount Reimbursed

61958150101 Sofosbuvir FFS 4 32 $902,257

61958150101 Sofosbuvir MC 4 112 $3,153,811

TOTAL 144 $4,056,068

Estimated number of patients treated 35 $115,888 per patient treated

Estimated number of patients cured 32 $126,752 per patient cured

DAA indicates direct-acting antiviral; FFS, fee-for-service; MC, managed care; NDC, National Drug Code.

ESTIMATED AVERAGE REBATE

No competition; assuming statutory rebate 23.1%


NDC Drug Name Plan Type Quarter Number of Prescriptions Medicaid Amount Reimbursed

61958150101 Sofosbuvir FFS 1 3231 $91,137,410

61958150101 Sofosbuvir MC 1 4928 $135,515,246

61958150101 Sofosbuvir FFS 2 7554 $210,574,435

61958150101 Sofosbuvir MC 2 11,304 $311,498,327

61958150101 Sofosbuvir FFS 3 4878 $132,596,531

61958150101 Sofosbuvir MC 3 10,248 $279,616,569

61958150101 Sofosbuvir FFS 4 2877 $76,365,177

61958150101 Sofosbuvir MC 4 6438 $170,173,407

TOTAL 51,458 $1,407,477,103

Estimated number of patients treated 12,450 $113,050 per patient treated

Estimated number of patients cured 11,454 $122,881 per patient cured

61958180101 Ledipasvir/sofosbuvir FFS 4 1198 $37,796,528

61958180101 Ledipasvir/sofosbuvir MC 4 1973 $59,623,522

TOTAL 3171 $97,420,049





No competition; assuming statutory rebate 23.1%


A P P E N D I X


NDC Drug Name Plan Type QuarterNumber of

Prescriptions Medicaid Amount

Reimbursed

61958150101 Sofosbuvir FFS 1 2083 $47,588,09861958150101 Sofosbuvir MC 1 3936 $95,133,18261958150101 Sofosbuvir FFS 2 2087 $46,614,01961958150101 Sofosbuvir MC 2 3917 $91,691,38761958150101 Sofosbuvir FFS 3 2530 $53,186,96561958150101 Sofosbuvir MC 3 4268 $94,634,38961958150101 Sofosbuvir FFS 4 3278 $66,797,15161958150101 Sofosbuvir MC 4 5128 $121,127,900TOTAL 27,227 $616,773,090Estimated number of patients treated 6587 $93,635 per patient treatedEstimated number of patients cured 6060 $101,778 per patient cured61958180101 Ledipasvir/sofosbuvir FFS 1 4792 $142,280,18661958180101 Ledipasvir/sofosbuvir MC 1 7612 $221,652,95061958180101 Ledipasvir/sofosbuvir FFS 2 7058 $201,833,22761958180101 Ledipasvir/sofosbuvir MC 2 13,206 $360,257,29961958180101 Ledipasvir/sofosbuvir FFS 3 7960 $192,538,74161958180101 Ledipasvir/sofosbuvir MC 3 15,276 $424,261,03861958180101 Ledipasvir/sofosbuvir FFS 4 8069 $187,380,68161958180101 Ledipasvir/sofosbuvir MC 4 15,839 $463,422,433TOTAL 79,812 $2,193,626,555Estimated Number of Patients Treated 19,309 $113,606 per patient treatedEstimated Number of Patients Cured 18,150 $120,861 per patient cured74309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir FFS 1 116 $3,212,47974309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir MC 1 187 $4,673,93574309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir FFS 2 919 $25,403,49474309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir MC 2 592 $14,046,61674309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir FFS 3 1551 $38,812,73074309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir MC 3 1238 $29,680,46874309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir FFS 4 2084 $48,160,51974309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir MC 4 1786 $43,500,586TOTAL 8473 $207,490,826Estimated number of patients treated 2050 $101,215 per patient treatedEstimated number of patients cured 1948 $106,515 per patient cured74308228 Ombitasvir/paritaprevir/ritonavir MC 3 14 $346,28074308228 Ombitasvir/paritaprevir/ritonavir FFS 4 27 $528,86874308228 Ombitasvir/paritaprevir/ritonavir MC 4 97 $2,339,708TOTAL 138 $3,214,856Estimated number of patients treated 41 $78,411 per patient treatedEstimated number of patients cured 41 $78,411 per patient cured



Competition emerges. Assuming ledipasvir/sofosbuvir are discounted to match ombitasvir/paritaprevir/ritonavir with dasabuvir + statutory rebate of 23.1%; others at statutory rebate.

31.0%

Estimated ledipasvir/sofosbuvir discount 34.0%

Ledipasvir/sofosbuvir market share 73.0%

Estimated average rebate 31.0%






Reimbursed

61958150101 Sofosbuvir FFS 1 3224 $67,412,718

61958150101 Sofosbuvir MC 1 4893 $116,056,853

61958150101 Sofosbuvir FFS 2 3264 $75,905,519

61958150101 Sofosbuvir MC 2 4998 $120,664,474

61958150101 Sofosbuvir FFS 3 2183 $52,992,235

61958150101 Sofosbuvir MC 3 4068 $101,952,054

61958150101 Sofosbuvir FFS 4 623 $15,534,476

61958150101 Sofosbuvir MC 4 1929 $48,264,745

TOTAL 25,182 $598,783,074




61958180101 Ledipasvir/sofosbuvir MC 1 16,309 $480,696,247







TOTAL 81,250 $2,228,739,399



74309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir FFS 1 1522 $35,631,974

74309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir MC 1 1694 $38,668,329







TOTAL 10,080 $245,677,877



74308228 Ombitasvir/paritaprevir/ritonavir FFS 1 25 $490,196

74308228 Ombitasvir/paritaprevir/ritonavir MC 1 66 $1,544,889

74308228 Ombitasvir/paritaprevir/ritonavir FFS 2 25 $542,383

74308228 Ombitasvir/paritaprevir/ritonavir MC 2 14 $354,347

74308228 Ombitasvir/paritaprevir/ritonavir MC 3 22 $567,272

TOTAL 152 $3,499,087



(continued)


A P P E N D I X

APPENDIX TABLE A5. (Continued) DAA Drug Utilization and Cost in Medicaid, 2016



Reimbursed

6307402 Elbasvir/grazoprevir FFS 1 11 $156,600

6307402 Elbasvir/grazoprevir MC 1 36 $597,437

6307402 Elbasvir/grazoprevir FFS 2 515 $6,346,104

6307402 Elbasvir/grazoprevir MC 2 1066 $16,504,369





TOTAL 14,901 $230,496,893



61958220101 Sofosbuvir/velpatasvir FFS 3 1436 $29,892,186

61958220101 Sofosbuvir/velpatasvir MC 3 2298 $69,138,818



TOTAL 15,513 $348,605,075



74006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir FFS 3 21 $517,758

74006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir MC 3 12 $303,910

74006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir FFS 4 288 $7,543,690

74006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir MC 4 68 $1,743,948

TOTAL 389 $10,109,306





Competition increases. Assuming all are discounted to match elbasvir/grazoprevir + statutory rebate of 23.1%. 59.5%

Estimated total net therapy cost $1,485,110,974

Total gross therapy cost $3,665,910,709






Reimbursed

61958150101 Sofosbuvir FFS 1 179 $4,079,14661958150101 Sofosbuvir MC 1 617 $15,079,55161958150101 Sofosbuvir FFS 2 93 $2,210,50861958150101 Sofosbuvir MC 2 269 $6,643,49461958150101 Sofosbuvir FFS 3 88 $2,327,05961958150101 Sofosbuvir MC 3 154 $3,386,57761958150101 Sofosbuvir FFS 4 51 $1,411,17861958150101 Sofosbuvir MC 4 82 $1,312,250TOTAL 1533 $36,449,763Estimated number of patients treated 371 $98,247 per patient treatedEstimated number of patients cured 341 $106,891 per patient cured61958180101 Ledipasvir/sofosbuvir FFS 1 6667 $181,585,53261958180101 Ledipasvir/sofosbuvir MC 1 6517 $182,287,49161958180101 Ledipasvir/sofosbuvir FFS 2 6784 $182,620,37461958180101 Ledipasvir/sofosbuvir MC 2 5814 $159,692,34861958180101 Ledipasvir/sofosbuvir FFS 3 5656 $151,868,85361958180101 Ledipasvir/sofosbuvir MC 3 4238 $117,385,51261958180101 Ledipasvir/sofosbuvir FFS 4 4942 $134,000,06961958180101 Ledipasvir/sofosbuvir MC 4 3503 $96,183,734TOTAL 44,121 $1,205,623,914Estimated number of patients treated 10,674 $112,950 per patient treatedEstimated number of patients cured 10,034 $120,154 per patient cured74309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir FFS 1 260 $7,033,36874309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir MC 1 744 $17,797,81574309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir FFS 2 181 $4,974,88074309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir MC 2 350 $7,986,95874309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir FFS 3 178 $4,990,62174309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir MC 3 142 $3,280,09774309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir FFS 4 136 $3,844,12974309328 Ombitasvir/paritaprevir/ritonavir with dasabuvir MC 4 91 $2,210,041TOTAL 2082 $52,117,908Estimated number of patients treated 504 $103,409 per patient treatedEstimated number of patients cured 479 $108,806 per patient cured74308228 Ombitasvir/paritaprevir/ritonavir MC 1 19 $489,10974308228 Ombitasvir/paritaprevir/ritonavir MC 2 18 $458,846TOTAL 37 $947,954Estimated number of patients treated 11 $86,178 per patient treatedEstimated number of patients cured 11 $86,178 per patient cured6307401 Elbasvir/grazoprevir MC 3 12 $220,3116307401 Elbasvir/grazoprevir MC 4 12 $220,1476307402 Elbasvir/grazoprevir FFS 1 2553 $36,441,8566307402 Elbasvir/grazoprevir MC 1 7235 $120,178,7446307402 Elbasvir/grazoprevir FFS 2 3044 $44,462,3916307402 Elbasvir/grazoprevir MC 2 10,626 $176,127,1186307402 Elbasvir/grazoprevir FFS 3 2896 $44,759,477




(continued)


A P P E N D I X


Competition increases further. Assuming all are discounted to match elbasvir/grazoprevir + statutory rebate of 23.1% for seven-twelfths of the year, all are discounted to match glecaprevir/pibrentasvir + statutory rebate of 23.1% for remaining five-twelfths of year.

54.1%




Reimbursed

TOTAL 43,347 $703,814,752Estimated number of patients treated 13,004 $54,123 per patient treatedEstimated number of patients cured 12,354 $56,971 per patient cured61958220101 Sofosbuvir/velpatasvir FFS 1 5033 $105,798,69361958220101 Sofosbuvir/velpatasvir MC 1 6897 $149,317,02661958220101 Sofosbuvir/velpatasvir FFS 2 5079 $104,792,21661958220101 Sofosbuvir/velpatasvir MC 2 8074 $178,215,16461958220101 Sofosbuvir/velpatasvir FFS 3 4166 $86,347,65161958220101 Sofosbuvir/velpatasvir MC 3 6874 $151,838,67761958220101 Sofosbuvir/velpatasvir FFS 4 3121 $66,955,79161958220101 Sofosbuvir/velpatasvir MC 4 4600 $101,428,232TOTAL 43,844 $944,693,450Estimated number of patients treated 13,153 $71,823 per patient treatedEstimated number of patients cured 12,364 $76,407 per patient cured74006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir FFS 1 414 $11,179,19874006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir MC 1 126 $2,823,71974006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir FFS 2 402 $10,844,10274006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir MC 2 394 $7,154,64674006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir FFS 3 395 $10,632,82574006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir MC 3 598 $8,425,09674006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir FFS 4 272 $7,376,96274006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir MC 4 588 $9,559,676TOTAL 3189 $67,996,225Estimated number of patients treated 772 $88,078 per patient treatedEstimated number of patients cured 733 $92,764 per patient cured61958240101 Sofosbuvir/velpatasvir/voxilaprevir FFS 3 46 $997,10061958240101 Sofosbuvir/velpatasvir/voxilaprevir MC 3 113 $2,617,43961958240101 Sofosbuvir/velpatasvir/voxilaprevir FFS 4 337 $7,247,63261958240101 Sofosbuvir/velpatasvir/voxilaprevir MC 4 568 $13,193,347TOTAL 1064 $24,055,517Estimated number of patients treated 319 $75,409 per patient treatedEstimated number of patients cured 303 $79,391 per patient cured74262528 Glecaprevir/pibrentasvir FFS 3 227 $2,218,05774262528 Glecaprevir/pibrentasvir MC 3 620 $7,837,88274262528 Glecaprevir/pibrentasvir MC 4 5703 $68,135,30874262528 Glecaprevir/pibrentasvir FFS 4 3184 $35,367,293TOTAL 9734 $113,558,540Estimated number of patients treated 3763 $30,178 per patient treatedEstimated number of patients cured 3725 $30,486 per patient cured







Reimbursed

61958150101 Sofosbuvir FFS 1 11 $307,827

61958150101 Sofosbuvir MC 1 44 $792,067

61958150101 Sofosbuvir FFS 2

61958150101 Sofosbuvir MC 2 25 $421,114

TOTAL 80 $1,521,008







TOTAL 7521 $207,806,074



74309328Ombitasvir/paritaprevir/ritonavir

with dasabuvirFFS 1 30 $859,312


with dasabuvirMC 1 46 $1,213,031


with dasabuvirFFS 1


with dasabuvirMC 2 15 $403,481

TOTAL 91 $2,475,823







TOTAL 3375 $56,407,835







TOTAL 11,942 $248,145,099



(continued)


A P P E N D I X

ESTIMATED AVERAGE REBATE (2018)

Competition steadied. Assuming all are discounted to match glecaprevir/pibrentasvir + statutory rebate of 23.1%. 50.6%

ESTIMATED AVERAGE REBATE (2019 AND BEYOND)

Competition steadied. Authorized generic of ledipasvir/sofosbuvir to enter at estimated price of $24,000 per patient. Assuming all will discount to match that price + 13% statutory rebate.

53.3%




Reimbursed

74006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir FFS 1 77 $2,116,543


74006328 Dasabuvir/ombitasvir/paritaprevir/ritonavir FFS 2


TOTAL 471 $8,734,790



61958240101 Sofosbuvir/velpatasvir/voxilaprevir FFS 1 314 $6,701,763

61958240101 Sofosbuvir/velpatasvir/voxilaprevir MC 1 607 $13,754,294

61958240101 Sofosbuvir/velpatasvir/voxilaprevir FFS 2 323 $6,908,328

61958240101 Sofosbuvir/velpatasvir/voxilaprevir MC 2 585 $9,719,076

TOTAL 1829 $37,083,460



74262528 Glecaprevir/pibrentasvir FFS 1 6953 $79,034,508

74262528 Glecaprevir/pibrentasvir MC 1 12,439 $146,951,125

74262528 Glecaprevir/pibrentasvir FFS 2 6245 $74,794,267

74262528 Glecaprevir/pibrentasvir MC 2 13,807 $137,351,287

TOTAL 39,444 $438,131,186




Patients with HCV who were cured of the disease were expected

to have HSU similar to that of otherwise comparable individuals

without the infection. Specifically, it was assumed that 90% of the

estimated average burden of illness would be eliminated by the cure.

The remaining 10% of HCV costs would likely be more than suffi-

cient to cover the recommended posttreatment monitoring of some

disease-free individuals, which may include HCV testing, ultrasound

examination, and endoscopy.8 Multiplying the cumulative number

of patients cured by the expected healthcare cost savings per person

per year yielded the total annual healthcare cost savings due to DAAs.

Total DAA expenditures (net of estimated rebates) were subtracted

from total avoided healthcare costs due to curing HCV to yield the

net financial impact of DAA use on Medicaid costs, derived annually

from 2013 through 2022. Forecasts for the remainder of 2018 through

2022 assumed DAA prices and utilization rates will remain unchanged

from their actual values in the first half of 2018. The cumulative net

impact of DAA utilization on healthcare costs was also derived and

was inflated to a common dollar year (2017) using the Consumer

Price Index for Medical Care.9 Finally, we also estimated the annual

number of health services averted by multiplying the associated

marginal effects from the burden of illness study by the cumula-

tive number of patients with HCV cured (see Appendix Table A8).

› CONTINUED FROM S142



ResultsBurden of Illness AnalysisAmong the 1,752,137 disabled individuals who met the inclusion

criteria described previously, 1,381,964 (78.9%) were enrolled in

managed care and 370,173 (21.1%) were in FFS plans. Nondisabled

adults were similarly split, with 2,752,261 (79.6%) in managed

care and 705,851 (20.4%) in FFS. A total of 72,109 were defined as

having chronic HCV, which represents a prevalence of 1.4% among

nonelderly adults in Medicaid. This rate was substantially higher

in the disabled (3.0%) than in the nondisabled adults group (0.6%).

The matching process yielded controls for 71,461 (99.1%) of the

identified patients with chronic HCV.

Appendix Table 1 presents mean values for all variables employed

in the matching process. Compared with nondisabled adults,

the disabled cohort was older, had more males, fewer whites

and Hispanics, and higher rates of HIV infection. The disabled

cohort was also more likely to have received cash assistance. The

highest percentages of study subjects resided in New York (26.4%),

California (20.5%), Ohio (7.2%), and Florida (6.6%). Several state/

plan type combinations contained no individuals (ie, managed

care in Alabama, Connecticut, and New Hampshire; and FFS in

Louisiana, Michigan, and Washington).

As reflected in Tables 2 and 3 of the main manuscript, 71.6% of

the disabled cohort and 86.8% of nondisabled adults were classified

as having noncirrhotic liver disease. Furthermore, disabled adults

with chronic HCV had higher percentages of both cirrhotic disease

(8.8% vs 4.8%) and ESLD (19.6% vs 8.4%) than nondisabled adults

with chronic HCV. Among both eligibility groups, these percent-

ages varied only slightly between FFS and managed care Medicaid

plans. Compared with their matched controls, disabled patients

with chronic HCV in FFS plans accounted for significantly more

annual inpatient hospitalizations (1.7 vs 0.5), hospital days (7.1 vs

2.5), ED visits (3.7 vs 1.7), physician’s office/clinic visits (8.7 vs 6.1),

and prescription drug fills (76.5 vs 67.7). The absolute differences

in HSU (ie, the marginal effects of chronic HCV) were very similar

for the disabled adults enrolled in managed care plans. Although

utilization was comparable for patients with chronic HCV and with

noncirrhotic and cirrhotic liver disease, it was dramatically higher

for those with ESLD. These patients were hospitalized on average

3.0 times per year for a total of 12.0 days, compared with 1.2 times

and 4.0 days per year for individuals with cirrhosis. Differences in

HSU across the liver disease severity cohorts among the disabled

adults in managed care largely mirrored those of the disabled

adults in FFS plans. All differences in means were highly statisti-

cally significant (P <.001).

Among nondisabled adults, those with chronic HCV in FFS plans

had significantly more hospitalizations (1.4 vs 0.4 for controls),

hospital days (6.6 vs 2.0), ED visits (2.6 vs 1.2), physician’s office/clinic

visits (4.8 vs 3.1), and prescription drug fills (40.1 vs 26.0). A similar

pattern of HSU emerged for nondisabled adults in managed care,

except that both the chronic HCV and control groups had fewer inpa-

tient hospital days and a greater number of outpatient visits. As with

the disabled patients, patients with ESLD had substantially greater

HSU. Annually, these patients averaged 2.9 hospitalizations for a

total of 13.4 days. In managed care, individuals with ESLD had even

more inpatient admissions (4.4) but fewer inpatient days (10.5). In

addition, ED visits were approximately double for patients with ESLD

compared with those with noncirrhotic and cirrhotic liver disease,

a result that also emerged among the disabled patients. Again, all

differences in means were highly statistically significant (P <.001).

Higher rates of HSU translated into substantially greater health-

care costs. As reported in Table 4 of the manuscript, mean annual

total costs were $53,159 per disabled patient with chronic HCV and

$35,280 for their controls without the disease. Nearly two-thirds of

the $17,879 in added expenditures were for inpatient hospitaliza-

tions ($11,142). Drug costs were greater by $5370, of which $1849

(34.4%) was for boceprevir and telaprevir and $1237 (23.0%) was

for peginterferon and ribavirin. Only 8.3% of patients were on this

interferon-based treatment regimen. Chronic HCV infection was also

associated with higher costs for physician services ($1203), outpa-

tient hospital visits ($1146), laboratory and x-ray costs ($810), clinic

visits ($589), psychiatric services ($365), transportation services

($313), and durable medical equipment ($95). These differences

were all highly statistically significant (P <.001). Conversely, nursing

facility, home health, and other services were lower by $368, $78,

and $736, respectively (P <.01). Across liver disease severity cohorts,

total healthcare costs were similar for noncirrhotic ($45,841) and

cirrhotic ($46,347) disease but were 69.6% higher for ESLD ($78,582).

Three-quarters of these additional costs were for inpatient services.

Nondisabled adults had lower cost levels than disabled adults,

but the incremental effect of chronic HCV was comparable. For

example, mean total healthcare costs were $26,788 for patients with

chronic HCV versus $9610 for the control group; this difference of

$17,178 is strikingly similar to the $17,789 estimate derived for the

disabled patients. Inpatient services, however, accounted for just

over one-third of this amount ($6263) instead of the two-thirds

measured for the disabled adults. Prescription drug spending was

higher by $6658, of which $3177 was for boceprevir and telaprevir and

$2265 was for the peginterferon and ribavirin treatment (received

by 14.4% of patients with chronic HCV). Moreover, expenditures

were greater for psychiatric services ($1242), outpatient hospital

visits ($732), clinic visits ($726), laboratory and x-ray services ($697),

physician visits ($437), durable medical equipment ($117), transpor-

tation services ($117), other services ($92), and home health services

($33). These cost differences were all statistically significant at the

P <.001 level except for home health (P <.01). Finally, in this cohort,

CONTINUED ON S154 ›


A P P E N D I X

APPENDIX TABLE A8. Impact of DAA Use on Healthcare Costs in Medicaid, 2013-2022 APPENDIX TABLE A8. (Continued) Impact of DAA Use on Healthcare Costs in Medicaid, 2013-2022

Drug Name 2013 2014 2015 2016 2017 Drug Name 2018 (proj) 2019 (proj) 2020 (proj) 2021 (proj) 2022 (proj)

Estimated Number of Patients With HCV Cured Estimated Number of Patients With Cured

Sofosbuvir 32 11,454 6060 5605 341 Sofosbuvir 34 34 34 34 34

Ledipasvir/sofosbuvir 0 721 18,150 18,478 10,034 Ledipasvir/sofosbuvir 3422 3422 3422 3422 3422

Ombitasvir/paritaprevir/ritonavir with dasabuvir 0 0 1948 2317 479 Ombitasvir/paritaprevir/ritonavir with dasabuvir 42 42 42 42 42

Ombitasvir/paritaprevir/ritonavir 0 0 41 46 11 Ombitasvir/paritaprevir/ritonavir 0 0 0 0 0

Elbasvir/grazoprevir 0 0 0 4247 12,354 Elbasvir/grazoprevir 1924 1924 1924 1924 1924

Sofosbuvir/velpatasvir 0 0 0 4375 12,364 Sofosbuvir/velpatasvir 6736 6736 6736 6736 6736

Dasabuvir/ombitasvir/paritaprevir/ritonavir 0 0 0 89 733 Dasabuvir/ombitasvir/paritaprevir/ritonavir 216 216 216 216 216

Sofosbuvir/velpatasvir/voxilaprevir 0 0 0 0 303 Sofosbuvir/velpatasvir/voxilaprevir 1044 1044 1044 1044 1044

Glecaprevir/pibrentasvir 0 0 0 0 3725 Glecaprevir/pibrentasvir 30,194 30,194 30,194 30,194 30,194

Total 32 12,175 26,199 35,157 40,344 Total 43,612 43,612 43,612 43,612 43,612

Cost of DAA Treatment (before rebates) Cost of DAA Treatment (before rebates)

Sofosbuvir $4,056,068 $1,407,477,103 $616,773,090 $598,783,074 $36,449,763 Sofosbuvir $3,042,016 $3,042,016 $3,042,016 $3,042,016 $3,042,016

Ledipasvir/sofosbuvir $0 $97,420,049 $2,193,626,555 $2,228,739,399 $1,205,623,914 Ledipasvir/sofosbuvir $415,612,148 $415,612,148 $415,612,148 $415,612,148 $415,612,148


$0 $0 $207,490,826 $245,677,877 $52,117,908Ombitasvir/paritaprevir/ritonavir with dasabuvir

$4,951,646 $4,951,646 $4,951,646 $4,951,646 $4,951,646

Ombitasvir/paritaprevir/ritonavir $0 $0 $3,214,856 $3,499,087 $947,954 Ombitasvir/paritaprevir/ritonavir $0 $0 $0 $0 $0

Elbasvir/grazoprevir $0 $0 $0 $230,496,893 $703,814,752 Elbasvir/grazoprevir $112,815,669 $112,815,669 $112,815,669 $112,815,669 $112,815,669

Sofosbuvir/velpatasvir $0 $0 $0 $348,605,075 $944,693,450 Sofosbuvir/velpatasvir $496,290,198 $496,290,198 $496,290,198 $496,290,198 $496,290,198

Dasabuvir/ombitasvir/paritaprevir/ritonavir $0 $0 $0 $10,109,306 $67,996,225 Dasabuvir/ombitasvir/paritaprevir/ritonavir $17,469,581 $17,469,581 $17,469,581 $17,469,581 $17,469,581

Sofosbuvir/velpatasvir/voxilaprevir $0 $0 $0 $0 $24,055,517 Sofosbuvir/velpatasvir/voxilaprevir $74,166,920 $74,166,920 $74,166,920 $74,166,920 $74,166,920

Glecaprevir/pibrentasvir $0 $0 $0 $0 $113,558,540 Glecaprevir/pibrentasvir $876,262,373 $876,262,373 $876,262,373 $876,262,373 $876,262,373

Total $4,056,068 $1,504,897,153 $3,021,105,327 $3,665,910,709 $3,149,258,024 Total $2,000,610,550 $2,000,610,550 $2,000,610,550 $2,000,610,550 $2,000,610,550

Estimated average rebate 23.1% 23.1% 31.0% 59.5% 54.1% Estimated average rebate 50.6% 53.3% 53.3% 53.3% 53.3%

Estimated Net Cost of DAA Treatment (after rebates) Estimated Net Cost of DAA Treatment (after rebates)

Total $3,119,116 $1,157,265,910 $2,083,964,594 $1,485,110,974 $1,445,203,541 Total $988,475,042 $934,129,440 $934,129,440 $934,129,440 $934,129,440

Estimated Healthcare Costs Savings Estimated Healthcare Costs Savings

HCV burden (PPPY) $15,808 $16,186 $16,612 $17,241 $17,674 HCV burden (PPPY) $17,674 $17,674 $17,674 $17,674 $17,674

Percentage of Burden Saved With Cure 90% 90% 90% 90% 90% Percentage of Burden Saved With Cure 90% 90% 90% 90% 90%

HCV burden savings (PPPY) $14,227 $14,567 $14,951 $15,517 $15,907 HCV burden savings (PPPY) $15,907 $15,907 $15,907 $15,907 $15,907

Cumulative number cured 32 12,207 38,406 73,563 113,907 Cumulative number cured 157,519 201,131 244,743 288,355 331,967

Total healthcare costs saved $455,266 $177,819,373 $574,189,210 $1,141,464,888 $1,811,873,086 Total healthcare costs saved $2,505,591,725 $3,199,310,365 $3,893,029,004 $4,586,747,643 $5,280,466,282

Net total healthcare cost savings –$2,663,850 –$979,446,537 –$1,509,775,384 –$343,646,086 $366,669,545 Net total healthcare cost savings $1,517,116,684 $2,265,180,925 $2,958,899,564 $3,652,618,203 $4,346,336,842

Net total savings (2017 dollars) –$2,978,324 –$1,069,517,673 –$1,606,326,228 –$352,278,093 $366,669,545 Net total savings (2017 dollars) $1,517,116,684 $2,265,180,925 $2,958,899,564 $3,652,618,203 $4,346,336,842

Cumulative net total savings (2017 dollars) –$2,978,324 –$1,072,495,997 –$2,678,822,225 –$3,031,100,318 –$2,664,430,772 Cumulative net total savings (2017 dollars) –$1,147,314,089 $1,117,866,836 $4,076,766,400 $7,729,384,603 $12,075,721,445

Estimated Health Services Avoided Estimated Health Services Avoided

Inpatient Hospitalizations 34 12,916 40,635 77,833 120,519 Inpatient hospitalizations 166,662 212,806 258,949 305,093 351,236

Inpatient Hospital Days 109 41,598 130,876 250,681 388,161 Inpatient hospital days 536,778 685,395 834,012 982,629 1,131,245

Emergency Department Visits 58 22,315 70,207 134,474 208,224 Emergency department visits 287,948 367,671 447,395 527,118 606,842

Physician’s Office/Clinic Visits 128 48,721 153,288 293,608 454,631 Physician’s Office/Clinic Visits 628,698 802,764 976,831 1,150,897 1,324,964

Prescription Drug Fills 363 138,370 435,342 833,857 1,291,167 Prescription Drug Fills 1,785,521 2,279,875 2,774,228 3,268,582 3,762,936

(Continued >>) DAA indicates direct-acting antiviral; proj, projected; HCV, hepatitis C virus; PPPY, per patient per year.



APPENDIX TABLE A8. Impact of DAA Use on Healthcare Costs in Medicaid, 2013-2022 APPENDIX TABLE A8. (Continued) Impact of DAA Use on Healthcare Costs in Medicaid, 2013-2022

Drug Name 2013 2014 2015 2016 2017 Drug Name 2018 (proj) 2019 (proj) 2020 (proj) 2021 (proj) 2022 (proj)

Estimated Number of Patients With HCV Cured Estimated Number of Patients With Cured

Sofosbuvir 32 11,454 6060 5605 341 Sofosbuvir 34 34 34 34 34

Ledipasvir/sofosbuvir 0 721 18,150 18,478 10,034 Ledipasvir/sofosbuvir 3422 3422 3422 3422 3422

Ombitasvir/paritaprevir/ritonavir with dasabuvir 0 0 1948 2317 479 Ombitasvir/paritaprevir/ritonavir with dasabuvir 42 42 42 42 42

Ombitasvir/paritaprevir/ritonavir 0 0 41 46 11 Ombitasvir/paritaprevir/ritonavir 0 0 0 0 0

Elbasvir/grazoprevir 0 0 0 4247 12,354 Elbasvir/grazoprevir 1924 1924 1924 1924 1924

Sofosbuvir/velpatasvir 0 0 0 4375 12,364 Sofosbuvir/velpatasvir 6736 6736 6736 6736 6736

Dasabuvir/ombitasvir/paritaprevir/ritonavir 0 0 0 89 733 Dasabuvir/ombitasvir/paritaprevir/ritonavir 216 216 216 216 216

Sofosbuvir/velpatasvir/voxilaprevir 0 0 0 0 303 Sofosbuvir/velpatasvir/voxilaprevir 1044 1044 1044 1044 1044

Glecaprevir/pibrentasvir 0 0 0 0 3725 Glecaprevir/pibrentasvir 30,194 30,194 30,194 30,194 30,194

Total 32 12,175 26,199 35,157 40,344 Total 43,612 43,612 43,612 43,612 43,612

Cost of DAA Treatment (before rebates) Cost of DAA Treatment (before rebates)

Sofosbuvir $4,056,068 $1,407,477,103 $616,773,090 $598,783,074 $36,449,763 Sofosbuvir $3,042,016 $3,042,016 $3,042,016 $3,042,016 $3,042,016

Ledipasvir/sofosbuvir $0 $97,420,049 $2,193,626,555 $2,228,739,399 $1,205,623,914 Ledipasvir/sofosbuvir $415,612,148 $415,612,148 $415,612,148 $415,612,148 $415,612,148


$0 $0 $207,490,826 $245,677,877 $52,117,908Ombitasvir/paritaprevir/ritonavir with dasabuvir

$4,951,646 $4,951,646 $4,951,646 $4,951,646 $4,951,646

Ombitasvir/paritaprevir/ritonavir $0 $0 $3,214,856 $3,499,087 $947,954 Ombitasvir/paritaprevir/ritonavir $0 $0 $0 $0 $0

Elbasvir/grazoprevir $0 $0 $0 $230,496,893 $703,814,752 Elbasvir/grazoprevir $112,815,669 $112,815,669 $112,815,669 $112,815,669 $112,815,669

Sofosbuvir/velpatasvir $0 $0 $0 $348,605,075 $944,693,450 Sofosbuvir/velpatasvir $496,290,198 $496,290,198 $496,290,198 $496,290,198 $496,290,198

Dasabuvir/ombitasvir/paritaprevir/ritonavir $0 $0 $0 $10,109,306 $67,996,225 Dasabuvir/ombitasvir/paritaprevir/ritonavir $17,469,581 $17,469,581 $17,469,581 $17,469,581 $17,469,581

Sofosbuvir/velpatasvir/voxilaprevir $0 $0 $0 $0 $24,055,517 Sofosbuvir/velpatasvir/voxilaprevir $74,166,920 $74,166,920 $74,166,920 $74,166,920 $74,166,920

Glecaprevir/pibrentasvir $0 $0 $0 $0 $113,558,540 Glecaprevir/pibrentasvir $876,262,373 $876,262,373 $876,262,373 $876,262,373 $876,262,373

Total $4,056,068 $1,504,897,153 $3,021,105,327 $3,665,910,709 $3,149,258,024 Total $2,000,610,550 $2,000,610,550 $2,000,610,550 $2,000,610,550 $2,000,610,550

Estimated average rebate 23.1% 23.1% 31.0% 59.5% 54.1% Estimated average rebate 50.6% 53.3% 53.3% 53.3% 53.3%

Estimated Net Cost of DAA Treatment (after rebates) Estimated Net Cost of DAA Treatment (after rebates)

Total $3,119,116 $1,157,265,910 $2,083,964,594 $1,485,110,974 $1,445,203,541 Total $988,475,042 $934,129,440 $934,129,440 $934,129,440 $934,129,440

Estimated Healthcare Costs Savings Estimated Healthcare Costs Savings

HCV burden (PPPY) $15,808 $16,186 $16,612 $17,241 $17,674 HCV burden (PPPY) $17,674 $17,674 $17,674 $17,674 $17,674

Percentage of Burden Saved With Cure 90% 90% 90% 90% 90% Percentage of Burden Saved With Cure 90% 90% 90% 90% 90%

HCV burden savings (PPPY) $14,227 $14,567 $14,951 $15,517 $15,907 HCV burden savings (PPPY) $15,907 $15,907 $15,907 $15,907 $15,907

Cumulative number cured 32 12,207 38,406 73,563 113,907 Cumulative number cured 157,519 201,131 244,743 288,355 331,967

Total healthcare costs saved $455,266 $177,819,373 $574,189,210 $1,141,464,888 $1,811,873,086 Total healthcare costs saved $2,505,591,725 $3,199,310,365 $3,893,029,004 $4,586,747,643 $5,280,466,282

Net total healthcare cost savings –$2,663,850 –$979,446,537 –$1,509,775,384 –$343,646,086 $366,669,545 Net total healthcare cost savings $1,517,116,684 $2,265,180,925 $2,958,899,564 $3,652,618,203 $4,346,336,842

Net total savings (2017 dollars) –$2,978,324 –$1,069,517,673 –$1,606,326,228 –$352,278,093 $366,669,545 Net total savings (2017 dollars) $1,517,116,684 $2,265,180,925 $2,958,899,564 $3,652,618,203 $4,346,336,842

Cumulative net total savings (2017 dollars) –$2,978,324 –$1,072,495,997 –$2,678,822,225 –$3,031,100,318 –$2,664,430,772 Cumulative net total savings (2017 dollars) –$1,147,314,089 $1,117,866,836 $4,076,766,400 $7,729,384,603 $12,075,721,445

Estimated Health Services Avoided Estimated Health Services Avoided

Inpatient Hospitalizations 34 12,916 40,635 77,833 120,519 Inpatient hospitalizations 166,662 212,806 258,949 305,093 351,236

Inpatient Hospital Days 109 41,598 130,876 250,681 388,161 Inpatient hospital days 536,778 685,395 834,012 982,629 1,131,245

Emergency Department Visits 58 22,315 70,207 134,474 208,224 Emergency department visits 287,948 367,671 447,395 527,118 606,842

Physician’s Office/Clinic Visits 128 48,721 153,288 293,608 454,631 Physician’s Office/Clinic Visits 628,698 802,764 976,831 1,150,897 1,324,964

Prescription Drug Fills 363 138,370 435,342 833,857 1,291,167 Prescription Drug Fills 1,785,521 2,279,875 2,774,228 3,268,582 3,762,936

(Continued >>) DAA indicates direct-acting antiviral; proj, projected; HCV, hepatitis C virus; PPPY, per patient per year.


A P P E N D I X

total healthcare costs rose dramatically with liver disease severity:

$23,411, $30,497, and $55,873 for patients with noncirrhotic disease,

cirrhotic disease, and ESLD, respectively (P <.001). As with the

disabled patients, the most pronounced increase was for inpatient

costs, which jumped from $7211 in the cirrhosis cohort to $30,720

in the ESLD cohort (P <.001). n

REFERENCES1. Mathematica Policy Research. Medicaid analytic eXtract anomaly tables 2012. CMS website. cms.gov/research-statistics-data-and-systems/computer-data-and-systems/medicaiddatasourcesgeninfo/maxgeneralinformation.html. Accessed January 27, 2018.

2. Gordon SC, Pockros PJ, Terrault NA, et al. Impact of disease severity on healthcare costs in patients with chronic hepatitis C (CHC) virus infection. Hepatology. 2012;56(5):1651-1660. doi: 10.1002/hep.25842.3. Kruskal WH, Wallis WA. Use of ranks in one-criterion variance analysis. J Am Stat Assoc. 1952;47:583-621. doi: 10.2307/2280779.4. Younossi ZM, Stepanova M, Henry L, Nader F, Younossi Y, Hunt S. Adherence to treatment of chronic hepatitis C: from interferon containing regimens to interferon and ribavirin free regimens. Medicine (Baltimore). 2016;95(28):e4151. doi: 10.1097/MD.0000000000004151.5. Slevin AR, Hart MJ, Van Horn C, et al. Hepatitis C virus direct-acting antiviral nonadherence: relation-ship to sustained virologic response and identification of at-risk patients. J Am Pharm Assoc (2003). 2019;59(1):51-56. doi: 10.1016/j.japh.2018.10.020.6. State drug utilization data. Medicaid website. medicaid.gov/medicaid/prescription-drugs/state-drug-utilization-data/index.html. Accessed December 3, 2018. 7. Medicaid drug rebate program. Medicaid website. medicaid.gov/medicaid/prescription-drugs/medicaid-drug-rebate-program/index.html. Updated November 13, 2018. Accessed January 9, 2019.8. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Monitoring patients who are starting HCV treatment, are on treatment, or have completed therapy. HCV Guidelines website. hcvguidelines.org/evaluate/monitoring. Updated May 24, 2018. Accessed April 12, 2019.9. Consumer price index. Bureau of Labor Statistics website. bls.gov/cpi/. Accessed May 1, 2019.

APPENDIX TABLE. Independent Variable Means by Chronic Hepatitis C Virus Cohort and Medicaid Plan Typea

Variable

Disabled Adults Nondisabled Adults

Fee-for-Service(N = 10,125)

Managed Care(N = 41,387)

Fee-for-Service(N = 4262)

Managed Care(N = 15,687)

Mean SD Mean SD Mean SD Mean SD

Age, in years 53.14 7.55 53.04 7.73 43.67 10.29 43.55 10.93

Male 0.57 0.50 0.55 0.50 0.50 0.50 0.45 0.50

White 0.59 0.49 0.52 0.50 0.75 0.43 0.60 0.49

Black 0.30 0.46 0.31 0.46 0.16 0.36 0.21 0.41

Other race 0.11 0.31 0.17 0.38 0.10 0.29 0.19 0.40

Hispanic 0.12 0.33 0.17 0.37 0.23 0.42 0.26 0.44

Any months in PCCM 0.40 0.49 0.05 0.21 0.21 0.41 0.03 0.16

Any months in cash MAS 0.74 0.44 0.92 0.27 0.26 0.44 0.37 0.48

Alabama 0.10 0.30 0.000 0.00 0.02 0.14 0.000 0.00

California 0.20 0.40 0.23 0.42 0.11 0.32 0.18 0.38

Connecticut 0.13 0.34 0.000 0.00 0.48 0.50 0.000 0.00

Florida 0.07 0.25 0.08 0.27 0.02 0.15 0.04 0.19

Illinois 0.22 0.41 0.01 0.10 0.19 0.39 0.002 0.05

Indiana 0.11 0.32 0.002 0.04 0.001 0.04 0.02 0.12

Louisiana 0.000 0.00 0.04 0.20 0.000 0.00 0.02 0.13

Michigan 0.000 0.00 0.07 0.25 0.000 0.00 0.03 0.18

New Hampshire 0.02 0.14 0.000 0.00 0.01 0.12 0.000 0.00

New Mexico 0.002 0.04 0.02 0.15 0.004 0.06 0.02 0.13

New York 0.10 0.31 0.23 0.42 0.14 0.34 0.50 0.50

Ohio 0.03 0.17 0.08 0.27 0.01 0.08 0.10 0.29

Oregon 0.000 0.02 0.04 0.19 0.000 0.02 0.02 0.14

Pennsylvania 0.01 0.08 0.09 0.28 0.001 0.03 0.03 0.18

Virginia 0.005 0.07 0.03 0.18 0.002 0.04 0.02 0.15

Washington 0.000 0.00 0.08 0.27 0.000 0.00 0.02 0.15

HIV+/AIDS 0.13 0.34 0.13 0.34 0.05 0.22 0.09 0.29

Asymptomatic HIV+ 0.04 0.20 0.04 0.21 0.01 0.11 0.04 0.19

MAS indicates maintenance assistance status; PCCM, primary care case management.aValues are proportions unless otherwise noted.

› CONTINUED FROM S151


N O T E S

SUPPLEMENT POLICY STATEMENTStandards for Supplements to The American Journal of Managed Care®

All supplements to The American Journal of Managed Care® are designed to facilitate and enhance ongoing medical education in various therapeutic disciplines. All Journal supplements adhere to standards of fairness and objectivity, as outlined below. Supplements to The American Journal of Managed Care® will:

I. Be reviewed by at least 1 independent expert from a recognized academic medical institution.

II. Disclose the source of funding in at least 1 prominent place.

III. Disclose any existence of financial interests of supplement contributors to the funding organization.

IV. Use generic drug names only, except as needed to differentiate between therapies of similar class and indication.

V. Be up-to-date, reflecting the current (as of date of publication) standard of care.

VI. Be visually distinct from The American Journal of Managed Care®.

VII. Publish information that is substantially different in form and content from that of the accompanying edition of The American Journal of Managed Care®.

VIII. Prohibit excessive remuneration for contributors and reviewers.

IX. Carry no advertising.

Publisher’s Note: The opinions expressed in this supplement are those of the authors, presenters, and/or panelists and are not attributable to the sponsor or the publisher, editor, or editorial board of The American Journal of Managed Care®. Clinical judgment must guide each professional in weighing the benefits of treat-ment against the risk of toxicity. Dosages, indications, and methods of use for products referred to in this supplement are not necessarily the same as indicated in the package insert for the product and may reflect the clinical experience of the authors, presenters, and/or panelists or may be derived from the professional literature or other clinical sources. Consult complete prescribing information before administering.

assessing the burden of illness of chronic hepatitis c and impact...

Documents