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Cost-effectiveness of Interferon-α2b Treatment for Hepatitis B e Antigen-Positive Chronic Hepatitis B

John B. Wong, MD; Raymond S. Koff, MD; Fabio Tine, MD; and Stephen G. Pauker, MD
[+] Article, Author, and Disclosure Information

From New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts. MetroWest Medical Center, Framingham, Massachusetts. V. Cervello Hospital, Palermo, Italy. Requests for Reprints: Stephen G. Pauker, MD, New England Medical Center, 750 Washington Street, Box 302, Boston, MA 02111. Disclaimer: Schering-Plough, the manufacturer of interferon-α2b, provided funding for this study but had no input regarding its content. The investigators retained full independence to publish the study results, regardless of the outcome of the analysis. Acknowledgments: The authors thank the advisory panel of experts for guidance and information. Panel members included Robert Carithers, MD (University of Washington); Marshall Kaplan, MD (New England Medical Center); Emmet B. Keeffe, MD (Stanford University); Robert P. Perrillo, MD (Ochsner Clinic); Fredric Regenstein, MD (Ochsner Clinic); Eugene Schiff, MD (University of Miami); and Leonard B. Seeff, MD (Veterans Affairs Medical Center, Washington, D.C.). Grant Support: In part by grant LM04493 from the National Library of Medicine, Bethesda, Maryland and a grant from Schering-Plough Laboratories. This research was done, in part, while Dr. Tine was a visiting physician at New England Medical Center and Tufts University School of Medicine.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;122(9):664-675. doi:10.7326/0003-4819-122-9-199505010-00004
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Objective: To estimate the cost-effectiveness of interferon-α2B for the treatment of patients with chronic hepatitis B infection who are positive for hepatitis B e antigen (HBeAg).

Design: Meta-analysis of nine randomized, controlled trials and cost-effectiveness analysis, projecting the clinical and economic outcomes expected from changes in serologic markers of hepatitis B viral replication.

Data Sources: MEDLINE search, expert panel opinion, hospital cost data, and adjusted physician charges.

Patients: 552 patients with confirmed chronic hepatitis B infection who were positive for HBeAg.

Intervention: Interferon-α2b.

Measurements: Lifetime incidence of cirrhosis and hepatocellular carcinoma; life expectancy; quality-adjusted life expectancy; and costs and marginal cost-effectiveness ratios from a societal perspective.

Results: Interferon-α2b increases the likelihood of becoming negative for HBeAg from 9.1% to 45.6% (difference, 36.5%; 95% CI, 23.7% to 49.2%) and of becoming negative for hepatitis B surface antigen from 1.7% to 7.7% (difference, 6.0%; CI, 2.8% to 9.3%) in the first year. For a 35-year-old person with chronic hepatitis B who is HBeAg positive, our analysis suggests that interferon-α2b will increase life expectancy by 3.1 years or 3.4 quality-adjusted life-years and will decrease projected lifetime costs, even if future savings are discounted; thus, interferon-α2b is the dominant strategy. Even with the model biased strongly in favor of standard care, the marginal cost-effectiveness ratio of interferon did not exceed $12 000 per life-year gained.

Conclusions: Interferon-α2b should prolong life and lower costs for patients with chronic hepatitis B who are HBeAg positive.


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Figure 1.
States of health in the decision model.

Each circle represents a state of health. The → represents the potential improved or worsened health status that might occur during a year. For example, a patient with chronic hepatitis may have a change in serologic markers or may develop cirrhosis. If the health status does not change, then patients remain in the same state of health (arrows not shown). The signifies that patients in any state of health may develop hepatocellular carcinoma or die. Dotted arrows represent transitions that occur at a low frequency. HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen.

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Figure 2.
Cumulative probability of developing cirrhosis, decompensated cirrhosis, or hepatocellular carcinoma with and without interferon therapy.

The lines represent the cumulative probabilities of developing these conditions.

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Figure 3.
Sensitivity analysis varying the probability of becoming negative for hepatitis B e antigen in the first year after interferon therapy.Top.Bottom.

The two lines in the top panel represent the quality-adjusted life expectancy afforded by each therapy. The preferred strategy corresponds to the higher line. The sharply curving line represents the marginal cost-effectiveness of interferon in discounted thousands of dollars per discounted quality-adjusted life-year gained (K$/DQALY). The ↓ denotes the baseline value for the probability of becoming negative for hepatitis B e antigen (HBeAg) (45.6%) in the first year after interferon therapy, and the horizontal bar represents the 95% CIs. As the probability of becoming HBeAg negative after interferon therapy approaches the probability occurring with standard care (9.1%), the benefit of interferon approaches zero and the marginal cost-effectiveness ratio approaches infinity.

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