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Original Research |

Cost-Effectiveness of Novel Regimens for the Treatment of Hepatitis C VirusCost-Effectiveness of New Regimens for Hepatitis C Virus

Mehdi Najafzadeh, PhD; Karin Andersson, MD; William H. Shrank, MD, MSHS; Alexis A. Krumme, MS; Olga S. Matlin, PhD; Troyen Brennan, MD, JD, MPH; Jerry Avorn, MD; and Niteesh K. Choudhry, MD, PhD
[+] Article, Author, and Disclosure Information

From Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, and Massachusetts General Hospital, Boston, Massachusetts, and CVS Health, Woonsocket, Rhode Island.

Acknowledgment: The authors thank Danielle L. Isaman, BS, for her administrative support.

Grant Support: By an unrestricted grant from CVS Health to Brigham and Women's Hospital. Dr. Najafzadeh received a Canadian Institutes of Health Research (CIHR) fellowship during the study.

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1152.

Reproducible Research Statement:Study protocol: Not applicable. Statistical code: Available from Dr. Najafzadeh (e-mail, mnajafzadeh@partners.org). Data set: Input parameters and sources are provided in the text.

Requests for Single Reprints: Niteesh K. Choudhry, MD, PhD, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120; e-mail, nchoudhry@partners.org.

Current Author Addresses: Drs. Najafzadeh, Avorn, and Choudhry and Ms. Krumme: Division of Pharmacoepidemiology and Pharmacoeconomics, 1620 Tremont Street, Suite 3030, Boston, MA 02120.

Dr. Andersson: Massachusetts General Hospital, 55 Fruit Street, Blake Building, Boston, MA 02114-2696.

Drs. Shrank and Brennan: CVS Health, One CVS Drive, Mailstop 4036, Woonsocket, RI 02895.

Dr. Matlin: CVS Health, 2211 Sanders Road, Northbrook, IL 60062.

Author Contributions: Conception and design: M. Najafzadeh, K. Andersson, W.H. Shrank, T. Brennan, N.K. Choudhry.

Analysis and interpretation of the data: M. Najafzadeh, W.H. Shrank, A.A. Krumme, J. Avorn, N.K. Choudhry.

Drafting of the article: M. Najafzadeh, A.A. Krumme, N.K. Choudhry.

Critical revision of the article for important intellectual content: M. Najafzadeh, W.H. Shrank, O.S. Martin, T. Brennan, J. Avorn, N.K. Choudhry.

Final approval of the article: M. Najafzadeh, K. Andersson, W.H. Shrank, O.S. Martin, J. Avorn, N.K. Choudhry.

Statistical expertise: M. Najafzadeh, N.K. Choudhry.

Obtaining of funding: O.S. Martin, T. Brennan, N.K. Choudhry.

Administrative, technical, or logistic support: W.H. Shrank, A.A. Krumme, O.S. Martin, T. Brennan, J. Avorn, N.K. Choudhry.

Collection and assembly of data: M. Najafzadeh, K. Andersson, W.H. Shrank.


Ann Intern Med. 2015;162(6):407-419. doi:10.7326/M14-1152
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This article has been corrected. The original version (PDF) is appended to this article as a Supplement.

Background: New regimens for hepatitis C virus (HCV) have shorter treatment durations and increased rates of sustained virologic response compared with existing therapies but are extremely expensive.

Objective: To evaluate the cost-effectiveness of these treatments under different assumptions about their price and efficacy.

Design: Discrete-event simulation.

Data Sources: Published literature.

Target Population: Treatment-naive patients infected with chronic HCV genotype 1, 2, or 3.

Time Horizon: Lifetime.

Perspective: Societal.

Intervention: Usual care (boceprevir–ribavirin–pegylated interferon [PEG]) was compared with sofosbuvir–ribavirin–PEG and 3 PEG-free regimens: sofosbuvir–simeprevir, sofosbuvir–daclatasvir, and sofosbuvir–ledipasvir. For genotypes 2 and 3, usual care (ribavirin–PEG) was compared with sofosbuvir–ribavirin, sofosbuvir–daclatasvir, and sofosbuvir–ledipasvir–ribavirin (genotype 3 only).

Outcome Measures: Discounted costs (in 2014 U.S. dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.

Results of Base-Case Analysis: Assuming sofosbuvir, simeprevir, daclatasvir, and ledipasvir cost $7000, $5500, $5500, and $875 per week, respectively, sofosbuvir–ledipasvir was cost-effective for genotype 1 and cost $12 825 more per QALY than usual care. For genotype 2, sofosbuvir–ribavirin and sofosbuvir–daclatasvir cost $110 000 and $691 000 per QALY, respectively. For genotype 3, sofosbuvir–ledipasvir–ribavirin cost $73 000 per QALY, sofosbuvir–ribavirin was more costly and less effective than usual care, and sofosbuvir–daclatasvir cost more than $396 000 per QALY at assumed prices.

Results of Sensitivity Analysis: Sofosbuvir–ledipasvir was the optimal strategy in most simulations for genotype 1 and would be cost-saving if sofosbuvir cost less than $5500. For genotype 2, sofosbuvir–ribavirin–PEG would be cost-saving if sofosbuvir cost less than $2250 per week. For genotype 3, sofosbuvir–ledipasvir–ribavirin would be cost-saving if sofosbuvir cost less than $1500 per week.

Limitation: Data are lacking on real-world effectiveness of new treatments and some prices.

Conclusion: From a societal perspective, novel treatments for HCV are cost-effective compared with usual care for genotype 1 and probably genotype 3 but not for genotype 2.

Primary Funding Source: CVS Health.

Figures

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Figure 1.

Model structure for one of the treatment groups.

This diagram shows one of the treatment groups in the model. Other treatment groups have the identical structure but different values for model parameters. The model assigns baseline characteristics (age, sex, race, alcohol use, METAVIR stage score, HCV genotype, IL-28B genotype, and age-specific quality of life) to a hypothetical cohort with HCV. Patients are assigned a treatment strategy and fibrosis stage (F0, F1, F2, F3, or F4) based on their METAVIR score. In each cycle, patients follow different health trajectories depending on whether they have achieved SVR, possible subsequent complications, liver-related death, or background mortality; probabilities of each are a function of patient characteristics in that cycle. If a patient survives in a given year, the quality-adjusted life-year and total cost accrued in that year will be recorded and patient characteristics will be updated for the next cycle. All patients are followed over their lifetime. Patients will receive only 1-time treatment, and re-treatment has not been modeled. HCC = hepatocellular carcinoma; HCV = hepatitis C virus; SVR = sustained virologic response.

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Appendix Figure 1.

Proportion of patients with no evidence of stage F0 fibrosis who developed stage F4 cirrhosis over time in the calibrated model.

A cohort of recently infected patients (i.e., at stage F0 fibrosis at baseline) were simulated over their lifetime, and their progression rates to cirrhosis over time were recorded. The characteristics of this cohort were identical to our assumptions in the base-case analysis, assuming that they received no treatment for hepatitis C virus. Under the base-case assumptions, 6.4% of patients developed cirrhosis over 25 y since infection.

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Figure 2.

Base-case results of incremental cost-effectiveness of treatment strategies versus usual care for genotypes 1 (top), 2 (middle), and 3 (bottom).

The lines represent the efficient frontier. The ICERs (compared with the next best alternative) have been reported for the points on the efficient frontier. Treatment options that are not on the efficient frontiers result in larger incremental costs and smaller incremental QALYs. DCV = daclatasvir; ICER = incremental cost-effectiveness ratio; LDV = ledipasvir; PEG = pegylated interferon; QALY = quality-adjusted life-year; RBV = ribavirin; SMV = simeprevir; SOF = sofosbuvir.

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Figure 3.

One-way sensitivity analyses on individual drug prices, identifying the threshold at which various treatment strategies become optimal in terms of net monetary benefit for genotypes 1 (top), 2 (middle), and 3 (bottom).

Dotted lines represent the values used in the base-case analyses. This sensitivity analysis assumes a willingness-to-pay threshold of $50 000 per quality-adjusted life-year. DCV = daclatasvir; LDV = ledipasvir; PEG = pegylated interferon; RBV = ribavirin; SMV = simeprevir; SOF = sofosbuvir.

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Figure 4.

One-way sensitivity analyses on SVR, identifying the threshold at which various treatment strategies become optimal in terms of net monetary benefit for genotypes 1 (top), 2 (middle), and 3 (bottom).

Dotted lines represent the values used in the base-case analyses. This sensitivity analysis assumes a willingness-to-pay threshold of $50 000 per quality-adjusted life-year. DCV = daclatasvir; LDV = ledipasvir; PEG = pegylated interferon; RBV = ribavirin; SMV = simeprevir; SOF = sofosbuvir; SVR = sustained virologic response.

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Appendix Figure 2.

Incremental cost-effectiveness ratio of treatment strategies versus usual care as a function of SVR rate for genotype 1 (top), 2 (middle), and 3 (bottom).

Usual care for genotype 1 consisted of response-guided triple therapy using boceprevir–RBV–PEG for 28 to 48 wk. Usual care for genotypes 2 and 3 consisted of dual therapy with RBV–PEG for 24 wk. DCV = daclatasvir; LDV = ledipasvir; PEG = pegylated interferon; QALY = quality-adjusted life-year; RBV = ribavirin; SMV = simeprevir; SOF = sofosbuvir; SVR = sustained virologic response.

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Appendix Figure 3.

ICERs as a function of baseline fibrosis stage, with results of a 1-way sensitivity analysis for genotypes 1 (top), 2 (middle), and 3 (bottom).

Usual care for genotype 1 consisted of response-guided triple therapy using boceprevir−RBV−PEG for 28 to 48 wk. Usual care for genotypes 2 and 3 consisted of dual therapy with ribavirin–PEG for 24 wk. DCV = daclatasvir; ICER = incremental cost-effectiveness ratio; LDV = ledipasvir; PEG = pegylated interferon; QALY = quality-adjusted life-year; RBV = ribavirin; SMV = simeprevir; SOF = sofosbuvir.

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Appendix Figure 4.

ICER of treatment strategies versus usual care as a function of age at treatment initiation for genotypes 1 (top), 2 (middle), and 3 (bottom).

Usual care for genotype 1 consisted of response-guided triple therapy using boceprevir–RBV–PEG for 28 to 48 wk. Usual care for genotypes 2 and 3 consisted of dual therapy with ribavirin–PEG for 24 wk. Because SOF–RBV is a dominated strategy for all ages, it has not been included. DCV = daclatasvir; ICER = incremental cost-effectiveness ratio; LDV = ledipasvir; PEG = pegylated interferon; QALY = quality-adjusted life-year; RBV = ribavirin; SMV = simeprevir; SOF = sofosbuvir.

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Appendix Figure 5.

Cost-effectiveness acceptability curve showing the optimal choices at various willingness-to-pay thresholds for genotypes 1 (top), 2 (middle), and 3 (bottom).

The plots represent the results of probabilistic sensitivity analyses using a Monte Carlo simulation, and the lines show the percentage of iterations in which each strategy would be optimal at various willingness-to-pay thresholds. Usual care for genotype 1 consisted of response-guided triple therapy using boceprevir–RBV–PEG for 28 to 48 wk. Usual care for genotypes 2 and 3 consisted of dual therapy with RBV–PEG for 24 wk. DCV = daclatasvir; LDV = ledipasvir; PEG = pegylated interferon; QALY = quality-adjusted life-year; RBV = ribavirin; SMV = simeprevir; SOF = sofosbuvir.

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Appendix Figure 6.

Results of probabilistic sensitivity analysis.

Cost-effectiveness acceptability curves of treatment strategies vs. usual care. Usual care for genotype 1 consisted of response-guided triple therapy using boceprevir–RBV–PEG for 28 to 48 wk. Usual care for genotypes 2 and 3 consisted of dual therapy with RBV–PEG for 24 wk. DCV = daclatasvir; LDV = ledipasvir; PEG = pegylated interferon; QALY = quality-adjusted life-year; RBV = ribavirin; SMV = simeprevir; SOF = sofosbuvir.

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