Treatment Alternatives for Chronic Hepatitis B Virus Infection: A Cost-Effectiveness Analysis

17 May 2005 | Volume 142 Issue 10 | Pages 821-831

Background: Treatment options for chronic hepatitis B virus (HBV) infection have disparate risks and benefits. Interferon has clinically significant side effects, and lamivudine is associated with viral resistance. In contrast, adefovir is safe and has lower viral resistance but is more expensive. The most cost-effective approach is uncertain.

Objective: To determine whether and under what circumstances the improved efficacy of adefovir offsets its increased cost compared with lamivudine or interferon.

Design: Cost–utility analysis stratified by hepatitis B e antigen (HBeAg) status.

Data Sources: Systematic review of MEDLINE from 1970 to 2005.

Target Population: Patients with chronic HBV infection, elevated aminotransferase levels, and no cirrhosis.

Time Horizon: Lifetime.

Perspective: Third-party payer.

Interventions: 1) No HBV treatment ("do nothing" strategy), 2) interferon monotherapy, 3) lamivudine monotherapy, 4) adefovir monotherapy, or 5) lamivudine with crossover to adefovir upon resistance ("adefovir salvage" strategy).

Outcome Measure: Incremental cost per quality-adjusted life-year (QALY) gained.

Results of Base-Case Analysis: The "do nothing" strategy was least effective yet least expensive. Compared with the "do nothing" strategy, using interferon cost an incremental $6337 to gain 1 additional QALY. Compared with interferon, the adefovir salvage strategy cost an incremental $8446 per QALY gained. Both the lamivudine and adefovir monotherapy strategies were more expensive yet less effective than the alternative strategies and were therefore dominated.

Results of Sensitivity Analysis: In sensitivity analysis, interferon was most cost-effective in health care systems with tight budgetary constraints and a high prevalence of HBeAg-negative patients.

Limitations: These results apply only to patients with chronic HBV infection, elevated aminotransferase levels, and no clinical or histologic evidence of cirrhosis. They do not apply to alternative populations.

Conclusions: Neither lamivudine nor adefovir monotherapy is cost-effective in chronic HBV infection. However, a hybrid salvage strategy reserving adefovir only for lamivudine-associated viral resistance may be highly cost-effective across most health care settings. Interferon therapy may still be preferred in health care systems with limited resources, especially in those serving populations with a high prevalence of HBeAg-negative HBV.

Editors' Notes Context Because current treatment options for chronic hepatitis B virus (HBV) infection have varying effects and costs, choosing among them is often difficult. Contribution Using a third-party payer perspective and lifetime horizon, this cost–utility analysis found that monotherapy with interferon but not lamivudine or adefovir was cost-effective. A salvage strategy that used adefovir only in case of lamivudine-associated viral resistance also seemed cost-effective. Cautions The findings apply only to patients with persistently elevated aminotransferase levels and no cirrhosis. The authors did not model the cost-effectiveness of nucleoside analogue salvage after interferon therapy failure. –The Editors

 

Author and Article Information

From Veterans Affairs Greater Los Angeles Healthcare System, David Geffen School of Medicine at University of California, Los Angeles, and Center for the Study of Digestive Healthcare Quality and Outcomes, Los Angeles, California; and Mount Sinai School of Medicine, New York, New York.

Acknowledgments: The authors thank Sun J. Kim for his assistance in conducting this study.

Grant Support: Dr. Kanwal is supported by a Veterans Administration Health Services Research & Development (VA HSR&D) Ambulatory Care Fellowship Award and an American Association for the Study of Liver Diseases Advanced Hepatology Fellowship Award. Dr. Gralnek is supported by a VA HSR&D Career Development Award and a VA HSR&D Merit Award (IIR 01-191-1). Dr. Dulai is supported by a National Institutes of Health NCRR K23 Award (RR-16188). Dr. Spiegel is supported by a VA HSR&D Career Development Award.

Potential Financial Conflicts of Interest: Consultancies: P. Martin (Gilead Sciences), B.M.R. Spiegel (Novartis); Honoraria: P. Martin (GlaxoSmithKline, Schering-Plough); Grants received: P. Martin (Schering-Plough, GlaxoSmithKline), B.M.R. Spiegel (Gilead Sciences).

Requests for Single Reprints: Brennan M.R. Spiegel, MD, MSHS, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, 11301 Wilshire Boulevard, Building 115, Room 215, Los Angeles, CA 90073; e-mail, BSpiegel{at}mednet.ucla.edu.

Current Author Addresses: Drs. Kanwal, Gralnek, Dulai, Farid, and Spiegel: VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, 11301 Wilshire Boulevard, Building 115, Room 215, Los Angeles, CA 90073.

Dr. Martin: Mount Sinai Medical Center, 1 Gustave Levy Place, New York, NY 10029.

Author Contributions: Conception and design: F. Kanwal, I.M. Gralnek, P. Martin, G.S. Dulai, B.M.R. Spiegel.

Analysis and interpretation of the data: F. Kanwal, B.M.R. Spiegel.

Drafting of the article: F. Kanwal, B.M.R. Spiegel.

Critical revision of the article for important intellectual content: F. Kanwal, P. Martin, G.S. Dulai.

Final approval of the article: F. Kanwal, I.M. Gralnek, P. Martin, G.S. Dulai, M. Farid, B.M.R. Spiegel.

Provision of study materials or patients: B.M.R. Spiegel.

Statistical expertise: F. Kanwal, B.M.R. Spiegel.

Administrative, technical, or logistic support: I.M. Gralnek.

Collection and assembly of data: F. Kanwal, I.M. Gralnek, M. Farid, B.M.R. Spiegel.

Read all Rapid Responses

Moving Away from Lamivudine Treatment in Hepatitis B

Gil Weitzman, Ira Jacobson, M.D.

Annals Online, 27 May 2005 [Full text]

Cost-effectiveness of the treatment of chronic hepatitis B

Harry L.A. Janssen, et al.

Annals Online, 27 Jun 2005 [Full text]

Avoid LAMIVUDINE Strategy for Chronic Hepatitis B

Aijaz Ahmed, et al.

Annals Online, 1 Jul 2005 [Full text]

Premature to Eliminate Lamivudine in the Treatment of Hepatitis B

Brennan M.R. Spiegel, et al.

Annals Online, 15 Jul 2005 [Full text]