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Original Investigation |

Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population

Harinder S. Chahal, PharmD, MSc1,2; Elliot A. Marseille, PhD2,3; Jeffrey A. Tice, MD4; Steve D. Pearson, MD, MSc5; Daniel A. Ollendorf, PhD5; Rena K. Fox, MD4; James G. Kahn, MD, MPH2,6
[+] Author Affiliations
1Department of Clinical Pharmacy, University of California, San Francisco
2Global Health Economics Consortium, San Francisco, California
3Health Strategies International, Oakland, California
4Division of General Internal Medicine, Department of Medicine, University of California, San Francisco
5Institute for Clinical and Economic Review, Boston, Massachusetts
6Institute for Health Policy Studies, University of California, San Francisco
JAMA Intern Med. 2016;176(1):65-73. doi:10.1001/jamainternmed.2015.6011.
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Importance  Novel treatments for hepatitis C virus (HCV) infection are highly efficacious but costly. Thus, many insurers cover therapy only in advanced fibrosis stages. The added health benefits and costs of early treatment are unknown.

Objective  To assess the cost-effectiveness of (1) treating all patients with HCV vs only those with advanced fibrosis and (2) treating each stage of fibrosis.

Design, Setting, and Participants  This study used a decision-analytic model for the treatment of HCV genotype 1. The model used a lifetime horizon and societal perspective and was representative of all US patients with HCV genotype 1 who had not received previous treatment. Comparisons in the model included antiviral treatment of all fibrosis stages (METAVIR [Meta-analysis of Histological Data in Virial Hepatitis] stages F0 [no fibrosis] to F4 [cirrhosis]) vs treatment of stages F3 (numerous septa without cirrhosis) and F4 only and by specific fibrosis stage. Data were collected from March 1 to September 1, 2014, and analyzed from September 1, 2014, to June 30, 2015.

Interventions  Six HCV therapy options (particularly combined sofosbuvir and ledipasvir therapy) or no treatment.

Main Outcomes and Measures  Cost and health outcomes were measured using total medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), calculated as the difference in costs between strategies divided by the difference in QALYs.

Results  We simulated 1000 individuals, but present the results normalized to a single HCV-infected person. In the base-case analysis, among patients receiving 8 or 12 weeks of sofosbuvir-ledipasvir treatment, treating all fibrosis stages compared with treating stages F3 and F4 adds 0.73 QALYs and $28 899, for an ICER of $39 475 per QALY gained. Treating at stage F2 (portal fibrosis with rare septa) costs $19 833 per QALY gained vs waiting until stage F3; treating at stage F1 (portal fibrosis without septa), $81 165 per QALY gained compared with waiting until stage F2; and treating at stage F0, $187 065 per QALY gained compared with waiting until stage F1. Results for other regimens show a similar pattern. At base-case drug prices, treating 50% of all eligible US patients with HCV genotype 1 would cost $53 billion. In sensitivity analyses, the ICER for treating all stages vs treating stages F3 and F4 was most sensitive to cohort age, drug costs, utility values in stages F1 and F2, and percentage of patients eligible for 8-week therapy. Except for patients aged 70 years, the ICER remains less than $100 000 per QALY gained. A 46% reduction in cost of sofosbuvir-ledipasvir therapy decreases the ICER for treating at all fibrosis stages by 48%.

Conclusions and Relevance  In this simulated model, treating HCV infection at early stages of fibrosis appeared to improve health outcomes and to be cost-effective but incurred substantial aggregate costs. The findings may have implications for health care coverage policies and clinical decision making.

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Figure 1.
Cases of Advanced Liver Disease Averted by Treating All Stages of Fibrosis vs Stages F3 and F4

Percentages were calculated per 100 000 treated patients using 100 000 Monte Carlo simulations. For every 100 000 patients treated (treatment naive, prevalent cohort aged 60 years), the percentage of the advanced liver disease cases that could be averted by treating all stages with combined sofosbuvir and ledipasvir for 8 or 12 weeks compared with treating stages F3 and F4 only are shown. By treating all stages of fibrosis vs waiting to treat at stages F3 and F4, the percentage of averted cases of liver transplant, decompensated cirrhosis, hepatocellular carcinoma, and liver death are 26%, 17%, 27%, and 25%, respectively. Fibrosis is measured using the METAVIR stages (described in the Model Overview subsection of the Methods section).

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Figure 2.
Sensitivity Analyses of Incremental Cost-effectiveness Ratios (ICERs) for Combined Sofosbuvir and Ledipasvir Treatment for All Stages of Fibrosis vs Stages F3 and F4

The tornado diagram depicts 1-way sensitivity analyses for the inputs with the greatest effect on the ICER. Bars to the right of the base-case ICER ($39 475 per quality-adjusted life-year [QALY] gained, represented by the vertical line) indicate an increase in the ICER relative to the base case to the upper limit of the input variable; bars to the left indicate the inverse. For example, as age increases from 20 years through the base-case age of 60 years to 70 years, the ICER increases. A high-to-low order of the range, as for the annual cost of treating stage F0 disease and no sustained virologic response (SVR), indicates an inverse relationship between the input value and the ICER. Fibrosis is measured using the METAVIR stages (described in the Model Overview subsection of the Methods section). Drug therapy indicates sofosbuvir-ledipasvir.

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Figure 3.
Cost-effectiveness Acceptability Curve for Combined Sofosbuvir and Ledipasvir Treatment for All Stages of Fibrosis vs Stages F3 and F4

Results of 10 000 Monte Carlo simulations (probabilistic sensitivity analysis) in which all input variables are varied simultaneously based on the listed ranges. The graph shows the percentage of simulations in which treating all patients (regardless of fibrosis stage) with sofosbuvir-ledipasvir for 8 or 12 weeks was considered cost-effective compared with treating only patients who reached fibrosis stages F3 and F4, depending on the willingness-to-pay (WTP) threshold. As the WTP increases (from left to right on the x-axis), the percentage of simulations resulting in treatment of all patients being cost-effective also increases. For example, for treatment at a WTP of $50 000 per quality-adjusted life-year (QALY), treating all patients is cost-effective in 74%; at a WTP of $150 000 per QALY, treating all patients is cost-effective in 96%. Fibrosis is measured using the METAVIR stages (described in the Model Overview subsection of the Methods section).

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Figure 4.
Budget Impact Analyses for Initial Treatment of Patients

The figure shows total drug costs for treating 25%, 50%, 75%, and 100% of the 1.37 million treatment-naive patients (identified during the next 5 years) with combined sofosbuvir and ledipasvir for 8 or 12 weeks. The analyses are subcategorized by treating all patients (treatment regardless of fibrosis stage) and treating only patients who reached stages F3 and F4. Offsets in savings in lifetime health care costs (exclusive of drug costs) achieved by treating all patients vs treating those with stages F3 and F4 are also shown. Fibrosis is measured using the METAVIR stages (described in the Model Overview subsection of the Methods section).

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