Emilio Frazzoli, Munther A. Dahleh and Eric Feron Jingru Luo.
Interferon-Based Therapies for Hepatitis C: Original ... · interferon alfacon-1). Dual combination...
Transcript of Interferon-Based Therapies for Hepatitis C: Original ... · interferon alfacon-1). Dual combination...
ABSTRACTBackground: Veterans using the Veterans Health Administration’s (VA's) services have a higher incidence of chronic hepatitis C virus (HCV) infection than the general population.
Objectives: To examine treatment patterns, direct costs associ-ated with interferon-based HCV therapy, and sustained virologic response (SVR) rates for genotypes 1 and 2.
Study Design: Retrospective review of utilization, cost, and outcome data for a cohort of 99 consecutive patients diagnosed with HCV receiving antiviral therapy beginning in January 2000 at a midwestern VA Medical Center.
Methods: Outpatient utilization and direct costs of clinical encounters and medications spanning calendar years 1997 to 2004 were extracted from VA administrative databases for 3 therapy combinations: interferon and ribavirin (IR); interferon, pegylated interferon, and ribavirin; and pegylated interferon and ribavirin (PR). Final costs were adjusted to 2010 prices. Identifying patients’ earliest diagnostic dates ensured analyses of treatment-naïve patients.
Results: Clinic visits and medications accounted for 20% and 80% of treatment costs respectively, regardless of genotype. Although genotype 1 patients’ treatment length and costs were substantially higher than those of non–genotype 1 patients, SVR rates were lower (31%) than those in non–genotype 1 patients (57%). Cost per SVR for genotype 1 patients ranged from $54,768 (IR) to $70,364 (PR). The overall cost per SVR for non–genotype 1 patients was $25,152.
Conclusions: Antiviral medications accounted for the majority of treatment costs. Cost per SVR was sensitive to genotype, effi cacy, and treatment duration. Utilization, costs, and outcomes associ-ated with interferon-based treatments serve as important baseline data for future comparative cost-effectiveness analyses.
(Am J Pharm Benefi ts. 2013;5(1):25-33)
Original Research
Since the hepatitis C virus (HCV) was fi rst identifi ed in
1989,1 it has become recognized as a common cause
of chronic liver disease around the world. Between
130 and 170 million people are chronically infected with
HCV worldwide and more than 350,000 die from HCV-relat-
ed liver disease annually.2 In the United States alone 1.6% of
the general population is seropositive for HCV antibodies,
and 1.3% (3.2 million individuals) have chronic hepatitis C.3
Currently, 36% of patients wait-listed for liver transplant in
the United States have chronic HCV infection.4 Over the next
decade, it is estimated that US direct medical care costs for
hepatitis C will range from $7 to $14 billion.5
Veterans have higher rates of HCV infection than the
general population.6 Patients with chronic hepatitis C in
the Veterans Health Administration (VA) system represent
a signifi cant number of patients; more than 147,000 active
patients with documented HCV viremia were in the VA HCV
Clinical Case Registry as of 2008.7 A 1999 national cross-
sectional study of more than 26,000 veterans receiving care
through the VA found a 6.6% point prevalence of HCV se-
ropositivity.8 A similar study conducted in 2001 reported
that 5.4% of VA users were seropositive for HCV antibod-
ies.9 Antiviral treatment for HCV is complex and has evolved
over time. In 1991, initial treatment consisted of interferon
alfa monotherapy (interferon alfa-2b, interferon alfa-2a, or
interferon alfacon-1). Dual combination therapy with inter-
feron alfa and ribavirin became available in 1998,10 and the
combination of pegylated interferon and ribavirin became
available beginning in 2001.11,12 Recently 2 new direct-acting
antiviral protease inhibitors, telaprevir and boceprevir, have
been approved for the treatment of patients with HCV geno-
type 1 infection in combination with pegylated interferon
and ribavirin.13-17
To date, treatment success is largely dependent on the
HCV genotype and duration of treatment. Six strains of
HCV have been identifi ed. Of these, genotype 1 is the most
At a GlancePractical Implications p 26
Author Information p 32
Full text and PDF www.ajpblive.com
Interferon-Based Therapies for Hepatitis C: Utilization, Costs, and Outcomes
Yvonne C. Jonk, PhD; Titilope Adeniyi, MS; Astrid Knott, PhD; Eric W. Dieperink, MD; and Samuel B. Ho, MD
www.ajpblive.com Vol. 5, No. 1 • The American Journal of Pharmacy Benefi ts 25 Vol. 5, No. 1 • The American Journal of Pharmacy Benefi ts
P R A C T I C A L I M P L I C A T I O N S
This study provides important baseline data for comparative cost-effectiveness analyses of therapeutic interventions to improve sus-tained virologic response (SVR) rates and reduce utilization and direct costs of clinical encounters and medications for hepatitis C patients.
� From 1997 to 2004, we compared 3 therapy combinations: inter-feron and ribavirin (IR); interferon, pegylated interferon, and ribavi-rin; and pegylated interferon and ribavirin (PR).
� Antiviral medications accounted for the majority of treatment costs.
� Compared with non–genotype 1 patients, genotype 1 patients had higher overall costs per SVR: $54,768 (IR) to $70,364 (PR) versus $25,152 (2010 dollars).
26 The American Journal of Pharmacy Benefi ts • January/February 2013 www.ajpblive.com
� Jonk • Adeniyi • Knott • Dieperink • Ho
prevalent in the United States, followed by genotypes
2 and 3 (collectively referred to as non–genotype 1).18
Genotype 1 is the most diffi cult strain to treat and gener-
ally requires treatment duration of 48 weeks. The recom-
mended treatment duration for patients with genotype 2
or 3 is 24 weeks.19,20 With currently available pegylated
interferon and ribavirin therapies, the sustained virologic
response (SVR) rates from registration trials associated
with treatment of genotype 1 is 42% to 46%, and with
treatment of genotypes 2 and 3 it is 76% to 82%.11,12 In
contrast, the actual SVR rate achieved in US veteran pa-
tients with HCV genotype 1 is 20%, while the SVR rates
for genotypes 2 and 3 are 52% and 43%, respectively.21
The newly approved therapies telaprevir and boceprevir
will require 24 to 48 weeks of treatment and are expected
to increase SVR rates.
In response to the rising number of HCV diagnoses,
the VA initiated a directive for implementing broad clini-
cal care programs for HCV, including routine screening
of all VA patients.22,23 As VA medical centers are reim-
bursed for caring for complex patients treated for HCV,
the cost associated with screening, treatment, and follow-
up for HCV patients is important to VA administrators.
Identifying strategies aimed at improving the quality and
cost-effectiveness of care provided to HCV patients is an
important administrative goal.
A number of studies in general populations of HCV
patients have found that dual therapy with interferon
and ribavirin can be considered cost-effective.24-28 Very
few studies have reported the actual costs incurred while
treating patients diagnosed with HCV infection,29 and
no studies have focused on VA costs. The most accurate
method to determine cost components is a “top down”
approach directly following a cohort and collecting actual
longitudinal frequency and unit cost data.30 The purpose
of this study was to examine the treatment patterns, di-
rect costs, and health outcomes associated with HCV an-
tiviral therapy in an actual VA HCV treatment population.
These data can then be used as baseline data for future
cost-effectiveness studies comparing current treatment
strategies with newly approved therapies.
METHODSA consecutive cohort of patients with chronic hepa-
titis C receiving antiviral treatment between January 1,
2000, and December 31, 2001, were identifi ed. During
this time period, 681 VA patients had a positive HCV en-
zyme-linked immunoassay test at a midwestern Depart-
ment of VA Medical Center (Figure). Of these patients,
557 did not receive antiviral therapy and were excluded
from the analysis. Patients who received experimental or
alternative therapies such as gamma interferon (n = 5)
or peginterferon antiviral monotherapy (n = 1) were also
excluded. Finally, additional patients were excluded due
to a lack of cost data (n = 17) or the inability to deter-
mine their genotype (n = 2), resulting in a fi nal sample
size of 99 patients treated for HCV with interferon-based
therapies.
Because some patients had been diagnosed prior to 2000,
we identifi ed the earliest diagnostic date in the patients’ ad-
ministrative records going back to 1997, thus ensuring that
the analyses pertained to patients who were treatment na-
ïve. Treatment start date for antiviral therapy was based on
the date of the fi rst prescription and the treatment duration
of the last prescription written by the physician.
Hepatitis C virus–related outpatient encounters, labs,
and biopsies were identifi ed using VA clinic stop code
307 for gastroenterology and the Current Procedural Ter-
minology (CPT) codes listed in Table 1. Each patient’s
HCV antiviral genotype, therapy combination, and treat-
ment length were examined. Patients were classifi ed as
either genotype 1 or non–genotype 1 patients. Three
therapy combinations were identifi ed: interferon and
ribavirin (IR); interferon, pegylated interferon, and riba-
virin (IPR); and pegylated interferon and ribavirin (PR).
These included the following medications: interferon
alfa-2b, ribavirin, combination of interferon alfa-2b and
ribavirin, pegylated interferon alfa-2a, and pegylated in-
terferon alfa-2b.
Using the VA’s clinic stop code 307 for gastroenterol-
ogy, the timeline used to identify associated HCV clinic
visits was defi ned as occurring 7 days prior to initiation of
antiviral therapy and 1.5 years after the prescription treat-
ment end date. The 1.5-year follow-up period was based
on the following clinical treatment regimen: HCV patients
The American Journal of Pharmacy Benefi ts • January/February 2013
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Interferon-Based Therapies for Hepatitis C
returned for a follow-up visit 6
months after completion of an-
tiviral therapy. Negative results
indicated SVR achievement,
and patients came in for a sec-
ond follow-up visit 1 year after
the initial 6-month follow-up
visit. If the 6-month HCV test
was positive, patients were re-
evaluated. Decisions regarding
a subsequent round of antiviral
treatment depended on the pa-
tients’ prior response and their
ability to tolerate side effects.
Physician recommendations
regarding other behavioral and
medical changes that would re-
duce fi brosis progression were
provided.
In order to accommodate
the range of therapeutic dura-
tion, treatment lengths of 1.5
times the expected number of weeks of medication therapy
were used to distinguish between patients undergoing 1
versus more than 1 course of treatment. Thus, genotype
1 patients were classifi ed as having either “greater than or
equal to” or “less than” 48 � 1.5 = 72 weeks of treatment.
Non–genotype 1 patients were classifi ed as having either
greater than or equal to or less than 24 � 1.5 = 36 weeks
of treatment.
Finally, regression analyses were used to address
factors predictive of differences in costs across the 3
Figure. Inclusion and Exclusion Criteria for Sample of VA Patients With Hepatitis C
681 HCV-positive patients
124 patients received AVT 557 patients did not receive AVT
118 received standard of care therapy 6 received experimental therapy(gamma interferon or PEG monotherapy)
101 had HERC outpatient cost data 17 had no HERC outpatient costs
99 patients—final sample 2 lacked information on genotype
AVT indicates antiviral therapy; HCV, hepatitis C virus; HERC, Health Economics Resource Center; PEG, pegylated interferon; VA, Veterans Health Administration.
Table 1. Laboratory CPT Codes Corresponding to HCV Clinic Visitsa
Lab or Biopsy CPT Code
Biopsy identifi cation 47000
Complete blood count 85027
Alanine aminotransferase 84460
Aspartate aminotransferase 84450
Alkaline phosphate 84075
Total bilirubin 82247
Creatinine 82565
Sodium potassium 84295, 84132
Albumin 82040
Glucose 82947
Thyroid-stimulating hormone 84443
Hepatitis C antibody 86803
Infectious agent detection by nucleic acid (DNA or RNA); hepatitis C, amplifi ed probe technique
87521 (qualitative)
Infectious agent detection by nucleic acid (DNA or RNA); hepatitis C, quantifi cation
87522 (quantitative)
CPT indicates Current Procedural Terminology; HCV, hepatitis C virus.aHCV clinic visits were identifi ed using Veterans Health Administration stop code 307 for gastroenterology.
28 The American Journal of Pharmacy Benefi ts • January/February 2013 www.ajpblive.com
� Jonk • Adeniyi • Knott • Dieperink • Ho
treatment groups. Because cost data are typically skewed
and not normally distributed, we estimated log expendi-
ture models that included indicator variables for the IPR
and PR groups. The largest group of IR patients served as
our reference category. Demographic data included age,
sex, marital status, service-connected status, genotype,
and treatment group. Service connection is determined
by the VA as an injury or disease incurred while serving
on active duty. Service-connected ratings vary from 0% to
100%, with higher ratings generally indicative of increas-
ing disease severity.
Data SourcesFor calendar years 1997 to 2004, clinical encounters
and laboratory tests were extracted from the VA’s Patient
Treatment and Outpatient Care fi les using VA clinic stop
codes and CPT codes. Patients’ demographic character-
istics, SVR status, genotype, and whether veterans were
service connected for injuries or disease incurred or ag-
gravated in military service were obtained by reviewing
patient medical records.
Outpatient costs were extracted from the Health Eco-
nomics Resource Center’s (HERC) Average Outpatient Cost
database. Because the HERC’s data sets are available only
from VA fi scal year 1999 onward (ie, October 1998 onward),
costs for outpatient encounters occurring prior to October
1998 were estimated using similar outpatient costs for en-
counters occurring after October 1998. Because the HERC’s
outpatient cost data are based on Medicare reimbursement
rates, the relative costs of clinic visits experienced by vet-
erans in each treatment regimen are comparable to those
in Medicare. Because VA costs are adjusted to refl ect the
VA’s overall annual budget, the actual dollar amounts for
specifi c healthcare events differ from those of Medicare.
Prescription medications and costs were derived from
the Veterans Health Information Systems and Technology
Architecture database. The costs for individual prescrip-
tions were calculated by multiplying the medication’s
unit price by the quantity supplied for that particular
prescription. All costs (medication and clinic visit) were
converted to 2010 prices using the Consumer Price Index
for medical care.31
This project was approved by an institutional review
board. The analyses were performed using SAS version
9.2 (SAS Institute Inc, Cary, North Carolina).
RESULTSDemographic Characteristics
The percentage of the study population who were
white (81%) and male (96%) closely resembles the gen-
eral VA patient population (Table 2); the study sample
of HCV patients was signifi cantly younger (49 years)
than the national 2001 VA average of 58 years, and more
likely to be divorced.32 As is characteristic of the general
US population of HCV patients,33 most veteran patients
(71/99, or 72%) were infected with the genotype 1 strain
of HCV.
Antiviral Medications and Costs Genotype 1 patients receiving IR therapy (n = 28) had
the lowest total medication cost ($12,188 per person),
with an overall duration of antiviral therapy of 63 weeks
(Table 3). Although patients receiving PR therapy (n =
24) had higher medication costs ($14,716) but shorter an-
tiviral treatment duration (32 weeks) compared with the
IR group, this difference was not signifi cant. On average,
genotype 1 patients requiring multiple treatments in the
IPR group (n = 19) had the longest antiviral treatment du-
ration (114 weeks) as well as the highest medication cost
of all 3 treatment groups ($23,517 per person) (P <.01). Concurrent with treatment guidelines, the treatment
regimen for non–genotype 1 patients was generally half
as long as that for genotype 1 patients. Subsequently,
medication costs for non–genotype 1 patients were 15%
to 24% lower than those of genotype 1 patients.
The American Journal of Pharmacy Benefi ts • January/February 2013
Table 2. Demographic Characteristics of HCV Patients Receiving Antiviral TherapyCharacteristic HCV Patients
Sample size 99
Sex, %
Male 96
Race/ethnicity, %
Caucasian 81
African American 10
American Indian/Alaskan Native 1
Unknown 7
Age, y
Range 39-70
Mean 49
Median 49
Marital status, %
Divorced 41
Married 32
Single 16
Separated 6
Widowed 4
HCV indicates hepatitis C virus.
www.ajpblive.com Vol. 5, No. 1 • The American Journal of Pharmacy Benefi ts 29
Interferon-Based Therapies for Hepatitis C
Across both genotypes, while 1 course of IR therapy
was typically longer than 1 course of PR therapy, IR
medication costs were 24% to 47% less expensive than
PR therapy (for genotype 1 patients, IR medications
cost $11,249 and PR medications cost $14,716; for non–
genotype 1 patients, IR medications cost $6681 and PR
medications cost $12,509). The extended duration of IR
therapy refl ects the attempt to increase SVR rates, as well
as the need for some patients with interrupted treatment
regimens to repeat the course of treatment. Independent
of genotype, patients experiencing more than 1 course
of IR therapy had higher costs than patients experienc-
ing PR therapy. Considering the additional medication
and clinical costs, multiple courses of IR therapy were
the second-most expensive treatment regimen overall
($22,439 for genotype 1; $21,642 for non–genotype 1).
The IPR subgroup primarily represents patients with IR
treatment relapses or failures who were transitioned to PR
therapy. Approximately 75% of patients (74% [14/19] of
genotype 1 patients; 80% [4/5] of non–genotype 1 patients)
experienced a signifi cant lapse in their treatment regimen
before transitioning to PR, while the remaining 25% did
not experience treatment delays while transitioning. The
extended treatment duration along with higher medica-
tion costs and more intensive clinical encounters resulted
in IPR patients comprising the most expensive treatment
group (P <.01).
Average Total Costs of Prescriptions and Outpatient Clinical Encounters
Over all treatment regimens, the average total cost
of antiviral therapy and HCV-related clinical encounters
was higher for genotype 1 patients ($19,660 per person)
than for non–genotype 1 patients ($14,373 per person)
(not shown). For each treatment regimen, the average
total cost of genotype 1 patients treated with IR, IPR, or
PR therapy was $15,647, $28,187, and $17,591 per per-
son, respectively, compared with $12,713, $20,856, and
$14,626 per person, respectively, for non–genotype 1 pa-
tients. Differences in cost were signifi cant between the
IPR and IR groups as well as between the IPR and PR
groups (P <.01 for both comparisons).
Cost per Sustained Virologic Response The overall HCV study population achieved an SVR rate
of 38% (38/99) (Table 4), resulting in an overall cost per
SVR of $47,324. Concurrent with the literature, non–geno-
type 1 patients achieved a higher SVR rate than the geno-
type 1 patients (57% [16/28] vs 31% [22/71], respectively).
Combined with lower treatment costs, it was generally
Table 3. Treatment Patterns and Cost for HCV Patients by Genotype and Therapy, 1997 to 2003a
Therapy Type
Average Length of Antiviral Therapy
(wk) (SD)
Average Cost of Antiviral Medication
per Person (SD)
Average Number of Clinic Visits
per Person (SD)
Average Cost of Visits
per Person (SD)Average Total Cost
per Person (SD)
Genotype 1
IR (n = 28) 63 (67) 12,188 (5059)b 35 (15) 3459 (1844)b 15,647 (5945)b
IR <72 wk (n = 24) 36 (14) 11,249 (4454) 33 (12) 3267 (1798) 14,516 (5099)
IR >72 wk (n = 4) 220 (19) 17,825 (5368) 52 (22) 4614 (1940) 22,439 (6860)
IPR (n = 19) 114 (68) 23,517 (10,488)b,c 46 (20) 4670 (2084)b,c 28,187 (11,575)b,c
IPR <72 wk (n = 5) 51 (12) 16,294 (5972) 28 (11) 2777 (608) 19,071 (5560)
IPR >72 wk (n = 14) 136 (65) 26,096 (10,681) 52 (19) 5346 (2007) 31,442 (11,516)
PR (n = 24) 32 (16) 14,716 (7233)c 26 (17) 2875 (1580)c 17,591 (7889)c
Non–genotype 1
IR (n = 20) 32 (22) 9964 (5859) 27 (15) 2751 (1232) 12,713 (6941)
IR <36 wk (n = 14) 22 (9) 6681 (2885) 20 (10) 2207 (978) 8888 (3628)
IR >36 wk (n = 6) 58 (21) 17,621 (2879) 45 (11) 4020 (721) 21,642 (3498)
IPR (n = 5) 99 (48) 17,866 (12,303) 23 (29) 2990 (2122) 20,856 (13,442)
IPR <36 wk (n = 1) 15 (NA) 3283 (NA) 12 (NA) 2493 (NA) 5776 (NA)
IPR >36 wk (n = 4) 120 (10) 21,512 (10,640) 26 (32) 3114 (2429) 24,627 (12,089)
PR (n = 3) 20 (20) 12,509 (13,157) 20 (21) 2118 (2315) 14,626 (15,438)
HCV indicates hepatitis C virus; IPR, interferon, pegylated interferon, and ribavirin; IR, interferon and ribavirin; NA, not applicable; PR, pegylated interferon and ribavirin.aCosts were adjusted for infl ation using the Consumer Price Index for medical care and represent 2010 dollars.bCosts for the IR group differ signifi cantly from those for the IPR group, P = .01.cCosts for the IPR group differ signifi cantly from those for the PR group, P = .01.
30 The American Journal of Pharmacy Benefi ts • January/February 2013 www.ajpblive.com
� Jonk • Adeniyi • Knott • Dieperink • Ho
more cost-effective to treat non–genotype 1 patients, with
an overall cost per SVR of $25,152. By contrast, the overall
cost per SVR for genotype 1 patients was $63,448.
The SVR rates for genotype 1 patients were similar for
IR and PR treatment groups. Interestingly, the SVR rate
for the IPR group was higher, possibly due to the longer
duration of therapy received; however, defi nite compari-
sons cannot be made due to the relatively small num-
bers of patients in each group. Across treatment groups,
costs per SVR for genotype 1 patients were $70,364 (PR),
$68,250 (IPR), and $54,768 (IR).
Costs per SVR for non–genotype 1 patients were
$34,761 (IPR) and $19,559 (IR). Note that there were too
few non–genotype 1 patients treated with PR to defi ni-
tively evaluate SVR rates.
Regression AnalysesAdjusting for differences in patient characteristics,
Table 5 lists the results for estimating the log expenditure
models. In the adjusted analyses, the IPR (P = .07) and
the PR (P = .03) groups incurred a signifi cantly higher
level of medication costs than the IR group. While the
costs associated with outpatient visits were not found
to signifi cantly differ across the 3 treatment groups, the
higher level of medication costs contributed to higher
total (outpatient and medication) costs for the IPR (P =
.06) and the PR (P = .07) groups relative to the IR group.
However, these differences were not signifi cant at the
P = .05 level. Generally speaking, across all treatment
groups, longer treatment duration was associated with
higher medication, outpatient, and total costs (P <.01).
DISCUSSIONAntiviral treatment of patients with HCV is intense and
complex, requiring many visits over the initial treatment
period of 24 to 48 weeks, as well as subsequent follow-up
visits and/or re-evaluation. Our data indicate that the total
overall costs related to treatment of patients with HCV
are highly dependent on genotype, medication costs, and
duration of therapy. Patients treated during periods that
include conversion of actively treated or previous treat-
ment failures to newer therapies, as represented by the
IPR group, have the longest duration and highest costs.
Despite these higher costs, the HCV genotype 1 patients
in this group demonstrated relatively high SVR rates, in-
dicating that there is a benefi t from more intensive care
during a period of changing protocols.
The greater number of visits (n = 33 visits) observed
with IR patients undergoing 1 course of therapy (<72
weeks) may be due to more favorable tolerability of
this regimen compared with PR (n = 26 visits) and an
attempt at a longer duration of treatment. Overall SVR
rates of 29% and 25% for IR and PR genotype 1 patients,
respectively, were comparable and better than national
estimates of 20% reported elsewhere.21
Largely due to the longer duration of the antiviral ther-
apy, it is more expensive to treat genotype 1 patients than
non–genotype 1 patients. Additionally, the higher SVR rate
in the non–genotype 1 group resulted in a lower cost per
cure ($25,152 per SVR) than that in the genotype 1 group
($63,448 per SVR). These results are comparable to those
reported by Malone et al.34 Comparing the outcomes of pa-
tients treated with pegylated interferon alfa-2b plus ribavirin
with the outcomes of patients treated with pegylated inter-
feron alfa-2a plus ribavirin, Malone et al estimated the cost
per SVR for treatment-naïve patients, 75% of whom were
genotype 1 patients, as $37,638 and $46,717, respectively
(ie, $47,146 and $58,518, respectively, in 2010 dollars).34
Finally, given that the annual cost of HIV treatment
in 1999 was $20,280 per patient (ie, $31,434 in 2010
dollars)35 and the 1-year event and angina-free cost of
coronary artery bypass grafting in 2001 was $14,095 (ie,
$20,070 in 2010 dollars),36 these results support the pri-
mary hypothesis that the direct cost of medical care asso-
ciated with the treatment and follow-up of HCV patients
is comparable to that of other chronic disorders.
Study LimitationsBecause our analysis of utilization and costs relied on
The American Journal of Pharmacy Benefi ts • January/February 2013
Table 4. Average Total Cost per Sustained Virologic Responsea
Therapy Type SVR Cost per SVR, $
Genotype 1
IR 8/28 (29%) 54,768
IPR 8/19 (42%) 68,250
PR 6/24 (25%) 70,364
Overall 22/71 (31%) 63,448
Non–genotype 1
IR 13/20 (65%) 19,559
IPR 3/5 (60%) 34,761
PR 0/3 (0%) NA
Overall 16/28 (57%) 25,152
Entire cohort 38/99 (38%) 47,324
IPR indicates interferon, pegylated interferon, and ribavirin; IR, interferon and ribavirin; PR, pegylated interferon and ribavirin; NA, not applicable; SVR, sustained virologic response.aCosts include medication and outpatient clinical encounters. Costs were adjusted for infl ation using the Consumer Price Index for medical care and represent 2010 dollars.
www.ajpblive.com Vol. 5, No. 1 • The American Journal of Pharmacy Benefi ts 31
Interferon-Based Therapies for Hepatitis C
the use of secondary administrative data sets, assump-
tions were made regarding the acceptability of time
lapses between multiple antiviral treatments and the time
frame for applicable clinic visits. In addition, we made
the assumption that all visits to the gastroenterology
clinic were related to HCV care, whereas some of these
encounters may have only been marginally related. Thus,
the cost per cure for the treatment regimens considered
in our analyses may be overstated. The costs per cure
could have been lower if some of the visits had been
determined not to be HCV related and were excluded
from our analyses. We also made the assumption that our
study population received care only at the VA. Because
the medications prescribed for patients diagnosed with
HCV are expensive, the treatment regimen is intense and
complex, and the patients tracked in this study received
care at the VA Medical Center throughout the duration of
the study, we believe that the likelihood of patients re-
ceiving care related to HCV outside the VA was minimal.
Thus, any bias associated with the use of non-VA care
was negligible. Because clinical encounters accounted
for only approximately 20% of the total cost of the care
provided, we believe that whatever bias was introduced
by the above limitations was minimal and did not af-
fect our conclusions. Moreover, our results appear to be
within the range of that estimated by other studies.
Our data are limited to inclusion of patients with HCV
who are patients at 1 VA Medical Center and may not
be generalizable to the nonveteran population. The VA
serves a fairly unique sector of the general population in
that veterans are largely white and male, and veterans
eligible to use VA services have open access to care with
no restrictions placed on referrals, specialists, or number
of visits.37 In addition, the VA receives larger pharmaceu-
tical discounts than the private market.38 Thus, medica-
tion costs will likely be higher in the private sector. To
illustrate this point, Yeh et al used data from a VA national
pharmacy database and from indirect expert opinion re-
garding the number of visits needed, and estimated that
the weekly costs of pegylated interferon plus ribavirin
in the VA system in 2005 ranged from $227 to $247 (ie,
$273-$297 in 2010 dollars), which was less than costs of
this regimen used in non-VA cost utility analyses ($433-
$817) (ie, $520-$982 in 2010 dollars).39 Because medica-
tion costs comprise approximately 80% of the cost of HCV
therapy, the relative cost-effectiveness of these therapies
may differ in the VA compared with the private sector.
Given these limitations, the results of this study may be
more applicable to patients in other large managed care
organizations receiving similar medication cost discounts.
Finally, inherently problematic in all observational stud-
ies is the issue of self-selection bias. Differences in costs and
SVR could be due to latent differences among the respective
patient groups themselves rather than to the treatment op-
tions. Although our study’s sample size limitations do not
lend themselves well to the traditional modes of correcting
for selection bias, at a minimum we conducted regression
analyses to account for measurable (observed) differences
using the data that we have on patient demographics, geno-
type, duration of treatment, and treatment type. Although
these analyses did not attempt to adjust for unobserved dif-
ferences in patient treatment groups, we believe that the
Table 5. Log Expenditure Models for Hepatitis C Patients (n = 99)a
Log (Medication Costs) Log (Outpatient Costs)Log (Total Outpatient and
Medication Costs)
Variable Parameter Estimate Pr >|t| Parameter Estimate Pr >|t| Parameter Estimate Pr >|t|
Intercept 4.02 <.0001b 3.51 <.0001b 4.09 <.0001b
Age −0.01 .32 −0.01 .33 −0.004 .37
Female −0.01 .97 0.03 .83 0.004 .98
Married 0.12 .04b 0.01 .82 0.09 .10
SC 50%-100% −0.08 .15 −0.06 .31 −0.07 .18
SC <50% −0.02 .75 0.09 .20 0.01 .86
Non–genotype 1 −0.09 .15 −0.10 .11 −0.09 .11
IPR 0.13 .07c 0.04 .58 0.12 .06c
PR 0.14 .03b −0.07 .29 0.10 .07c
Treatment duration (wk) 0.003 <.0001b 0.002 .001b 0.002 <.0001b
IPR indicates interferon, pegylated interferon, and ribavirin; PR, pegylated interferon and ribavirin; Pr >|t|, P value for a 2-tail test; SC, service connected.aIR (interferon and ribavirin) is the reference category for treatment group. Boldfacing indicates signifi cant results. bSignifi cant at the P = .05 level.cSignifi cant at the P = .10 level.
32 The American Journal of Pharmacy Benefi ts • January/February 2013 www.ajpblive.com
� Jonk • Adeniyi • Knott • Dieperink • Ho
analyses refl ect what the consulting provider considered an
appropriate treatment regimen given the patient’s history
and diagnosis. In the absence of a randomized controlled
trial, we believe that this analysis is useful in that it assesses
the observed cost of caring for HCV patients in one of the
largest managed care organizations in the United States.
Policy Implications In 2011, telaprevir and boceprevir became available
for treatment in combination with the standard of care,
PR, for treatment of patients with HCV genotype 1. Cur-
rent phase III clinical trials indicate an up to 2-fold im-
provement in SVR rates to 68% to 75% for genotype 1
HCV patients, and a 2- to 5-fold increase in SVR rates to
53% for genotype 1 nonresponders to standard PR treat-
ment.13-17 The timing of visits and laboratory monitoring
for these regimens are equivalent to visits required for
current interferon-based treatments, and the majority of
patients treated will require 24 weeks of treatment rather
than 48 weeks.13-17 New cost-effectiveness analyses will
be needed to take into account the improved effi cacy and
the increased costs associated with these novel drugs. The
current data regarding the actual treatment-related costs
of resource use for patients receiving 24 to 48 weeks of
interferon-based treatments are relevant to future cost-
effectiveness analyses using these new combinations.
Author Affi liations: From Rural Health Research Center (YCJ), Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, MN; Division of Health Policy and Management (YCJ, TA), School of Public Health, University of Minnesota, Minneapolis, MN; Hepatitis C Resource Center (AK, EWD), Minneapolis VA Health Care System, Minneapolis, MN; San Diego VA Healthcare Sys-tem (SBH), San Diego, CA.
Author Disclosures: Dr Ho reports receiving grants from Veterans Affairs, Genentech, Vital Therapies, and Aspire Bariatrics. The other au-thors (YCJ, TA, AK, EWD) report no relationship or fi nancial interest with any entity that would pose a confl ict of interest with the subject matter of this article.
Authorship Information: Concept and design (YCJ, TA, EWD, SBH); acquisition of data (YCJ, TA, SBH); analysis and interpretation of data (YCJ, TA, EWD); drafting of the manuscript (YCJ, TA, AK); critical re-vision of the manuscript for important intellectual content (YCJ, TA, AK, EWD, SBH); statistical analysis (YCJ, TA); provision of study materials or patients (EWD); obtaining funding (YCJ, EWD, SBH); administrative, technical, or logistic support (AK, EWD); and supervision (YCJ, SBH).
Funding Source: This study was funded in part through the Harold Hartman Hepatitis C Award from the Minnesota Veterans Research Insti-tute, Minneapolis, MN, and the Hepatitis C Resource Centers of the Pub-lic Health Strategic Health Care Group, Department of Veterans Affairs.
Address correspondence to: Yvonne C. Jonk, PhD, Senior Re-search Associate, Rural Health Research Center, University of Minne-sota, 2520 University Ave SE, Ste 201, Minneapolis, MN 55414. E-mail: [email protected].
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