B- CRF: infectious diseases including vaccine
F- 08: infectious complications
The Cost-Effectiveness of Sofosbuvir-Based Regimens for Treatment
of Hepatitis C Virus Genotype 2 or 3 Infection
Benjamin P. Linas, MD, MPH; Devra M. Barter, MS; Jake R. Morgan, MS; Mai T. Pho, MD, MPH;
Jared A. Leff, MS; Bruce R. Schackman, PhD; C. Robert Horsburgh, MD, MUS; Sabrina A.
Assoumou, MD, MPH; Joshua A. Salomon, PhD; Milton C. Weinstein, PhD; Kenneth A.
Freedberg, MD, MSc; and Arthur Y. Kim, MD
Journal : Ann Intern Med.
Year : 2015 / Month : May
Volume : 162
Pages : 619-629.
DOI:10.7326/M14-1313
ABSTRACT
Background
Chronic infection with hepatitis C virus (HCV) genotype 2 or 3 can be treated with sofosbuvir
without interferon. Because sofosbuvir is costly, its benefits should be compared with the
additional resources used.
Objective
To estimate the cost-effectiveness of sofosbuvir-based treatments for HCV genotype 2 or 3
infection in the United States.
Design
Monte Carlo simulation, including deterministic and probabilistic sensitivity analyses.
Data Sources
Randomized trials, observational cohorts, and national health care spending surveys.
Target Population
8 patient types defined by HCV genotype (2 vs. 3), treatment history (naive vs. experienced), and
cirrhosis status (noncirrhotic vs. cirrhotic).
Time Horizon
Lifetime.
Perspective
Payer.
Intervention
Sofosbuvir-based therapies, pegylated interferon–ribavirin, and no therapy.
Outcome Measures: Discounted quality-adjusted life-years (QALYs), costs, and incremental
cost-effectiveness ratios (ICERs).
Results of Base-Case Analysis
The ICER of sofosbuvir-based treatment was less than $100 000 per QALY in cirrhotic patients
(genotype 2 or 3 and treatment-naive or treatment-experienced) and in treatment-experienced
noncirrhotic patients but was greater than $200 000 per QALY in treatment-naive noncirrhotic
patients.
Results of Sensitivity Analysis
The ICER of sofosbuvir-based therapy for treatment-naive noncirrhotic patients with genotype 2
or 3 infection was less than $100 000 per QALY when the cost of sofosbuvir was reduced by
approximately 40% and 60%, respectively. In probabilistic sensitivity analyses, cost-effectiveness
conclusions were robust to uncertainty in treatment efficacy.
Limitation
The analysis did not consider possible benefits of preventing HCV transmission.
Conclusion
Sofosbuvir provides good value for money for treatment-experienced patients with HCV genotype
2 or 3 infection and those with cirrhosis. At their current cost, sofosbuvir-based regimens for
treatment-naive noncirrhotic patients exceed willingness-to-pay thresholds commonly cited in the
United States.
Primary Funding Source
National Institute on Drug Abuse and National Institute of Allergy and Infectious Diseases.
COMMENTS.
Sofosbuvir, a nucleotide analogue inhibitor of hepatitis C virus (HCV) NS5B polymerase with
activity against all HCV genotypes. In combination with ribavirin, sofosbuvir can be used to treat
patients with chronic HCV genotype 2 or 3 infection without interferon, yielding cure rates greater
than with the previous standard of care.
Cure, also known as sustained virologic response (SVR), is associated with a greatly reduced
lifetime risk for liver-related morbidity and mortality and increased short-term survival for patients
with advanced liver disease (cirrhosis and cancer). These are very spectacular results, obtained
without interferon therapy which is frequently toxic.
Nethertheless, sofosbuvir currently costs approximately $1000 per tablet, or $28 000 for 4 weeks
in the USA. Several state Medicaid programs recently announced that sofosbuvir will be available
only to patients with advanced liver disease.
The goal of the studyl was to evaluate the cost-effectiveness of sofosbuvir-based treatment
strategies for patients with HCV genotype 2 or 3 infection to identify approaches that would
maximize the number of patients who achieve HCV cure, given competing demands on
resources.
A model was constructed and performed analyses were made using TreeAge Pro 2012 software
(TreeAge Software).
Quality of life (QoL) reflected the combination of 3 independent utility functions, which were
combined multiplicatively. First, was considered utility related to non-HCV comorbid conditions;
all simulated persons had a “background” QoL that was a function of age and sex. Second, was
considered HCV-specific utility; HCV-related QoL was a function of fibrosis stage, with
progressively lower utility with advancing disease. Third, was considered treatment-related utility.
All patients had decreased QoL while receiving HCV therapy, which reflected the disutility of
treatment adverse effects. Quality of life during interferon-free treatment was higher (multiplier,
0.99) than during therapy involving interferon (multiplier, 0.88).
At its current cost, sofosbuvir-based HCV therapy improves outcomes and provides good
economic value in patients with cirrhosis and genotype 2 or 3 infection and in those who were
previously treated with interferon. However, in treatment-naive noncirrhotic patients, for whom
pegylated interferon–ribavirin remains a treatment option, the ICER of sofosbuvir-based therapy
for genotype 2 or 3 infection is well over $100 000 per QALY. These conclusions were robust to
sensitivity analyses that incorporated uncertainty around treatment efficacy, mortality, QoL, and
costs.
In summary, this analysis shows that at its current U.S. cost of $28 000 for 4 weeks of therapy,
sofosbuvir-based treatment for HCV genotype 2 or 3 infection extends QALE and provides good
value for money in cirrhotic patients and in treatment-experienced patients. Among treatmentnaive noncirrhotic patients, however, the ICER of sofosbuvir-based treatments exceeds the
commonly cited U.S. willingness-to-pay threshold of $100 000 per QALY gained. One option for
using sofosbuvir is to treat only cirrhotic patients and those who have previously not benefitted
from interferon:
To conclude, the Editor outlines the following points:
 Sofosbuvir effectively treats chronic infection with hepatitis C virus (HCV) genotype 2 or 3 but
is expensive.
 The investigators used models to estimate the cost-effectiveness of alternative therapies and
found that sofosbuvir is worth the extra cost when compared with the combination of
pegylated interferon and ribavirin for some patients.
 This type of analysis requires many assumptions.
 Sofosbuvir provides good value for patients with HCV genotype 2 or 3 infection when the
patient has cirrhosis or when the patient does not have cirrhosis but has not benefitted
from other treatments
Pr. Jacques CHANARD
Professor of Nephrology