Tenofovir and Entecavir Are the Most Effective Antiviral Agents for Chronic Hepatitis B: A Systematic Review and Bayesian Meta-analyses

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Tenofovir and Entecavir Are the Most Effective Antiviral Agents for Chronic

Hepatitis B: A Systematic Review and Bayesian Meta-analyses

Gloria Woo

AffiliationsToronto Health Economics and Technology Assessment Collaborative,

University of Toronto, Toronto, Ontario, CanadaDepartments of Medicine and

Health Policy, Management and Evaluation, and Faculty of Pharmacy, University of

Toronto, Toronto, Ontario, CanadaReprint requests Address requests for reprints

to: Gloria Woo, PhD, Department of Pharmaceutical Sciences, University of

Toronto, 144 College Street, Suite 658, Toronto, Ontario M5S 3M2, Canada. fax:

(416) 946-3719

, Tomlinson

AffiliationsToronto Health Economics and Technology Assessment Collaborative,

University of Toronto, Toronto, Ontario, CanadaDepartments of Medicine and

Health Policy, Management and Evaluation, and Faculty of Pharmacy, University of

Toronto, Toronto, Ontario, CanadaUniversity Health Network, Toronto General

Research Institute and Clinical Studies Resource Centre Toronto Western Research

Institute, Toronto, Ontario, Canada

, Yasunori Nishikawa

AffiliationsToronto Health Economics and Technology Assessment Collaborative,

University of Toronto, Toronto, Ontario, Canada

, Kowgier

AffiliationsToronto Health Economics and Technology Assessment Collaborative,

University of Toronto, Toronto, Ontario, Canada

, Sherman

AffiliationsDepartments of Medicine and Health Policy, Management and

Evaluation, and Faculty of Pharmacy, University of Toronto, Toronto, Ontario,

CanadaUniversity Health Network, Toronto General Research Institute and Clinical

Studies Resource Centre Toronto Western Research Institute, Toronto, Ontario,

Canada

, K.H. Wong

AffiliationsDepartments of Medicine and Health Policy, Management and

Evaluation, and Faculty of Pharmacy, University of Toronto, Toronto, Ontario,

CanadaUniversity Health Network, Toronto General Research Institute and Clinical

Studies Resource Centre Toronto Western Research Institute, Toronto, Ontario,

Canada

, Ba Pham

AffiliationsToronto Health Economics and Technology Assessment Collaborative,

University of Toronto, Toronto, Ontario, CanadaDepartments of Medicine and

Health Policy, Management and Evaluation, and Faculty of Pharmacy, University of

Toronto, Toronto, Ontario, Canada

, J. Ungar

AffiliationsToronto Health Economics and Technology Assessment Collaborative,

University of Toronto, Toronto, Ontario, CanadaDepartments of Medicine and

Health Policy, Management and Evaluation, and Faculty of Pharmacy, University of

Toronto, Toronto, Ontario, CanadaHospital for Sick Children Research Institute,

Toronto, Ontario, Canada

, R. Einarson

AffiliationsToronto Health Economics and Technology Assessment Collaborative,

University of Toronto, Toronto, Ontario, CanadaDepartments of Medicine and

Health Policy, Management and Evaluation, and Faculty of Pharmacy, University of

Toronto, Toronto, Ontario, Canada

, E. Heathcote

AffiliationsDepartments of Medicine and Health Policy, Management and

Evaluation, and Faculty of Pharmacy, University of Toronto, Toronto, Ontario,

CanadaUniversity Health Network, Toronto General Research Institute and Clinical

Studies Resource Centre Toronto Western Research Institute, Toronto, Ontario,

Canada

, Murray Krahn

AffiliationsToronto Health Economics and Technology Assessment Collaborative,

University of Toronto, Toronto, Ontario, CanadaDepartments of Medicine and

Health Policy, Management and Evaluation, and Faculty of Pharmacy, University of

Toronto, Toronto, Ontario, CanadaUniversity Health Network, Toronto General

Research Institute and Clinical Studies Resource Centre Toronto Western Research

Institute, Toronto, Ontario, Canada

Received 30 July 2009; accepted 4 June 2010. published online 21 June 2010.

Abstract

Background & Aims

The relative efficacies of licensed antiviral therapies for treatment-naive

chronic hepatitis B (CHB) infection in randomized controlled trials have not

been determined. We evaluated the relative efficacies of the first 12 months of

CHB treatments.

Methods

Drugs evaluated were lamivudine, pegylated interferon, adefovir, entecavir,

telbivudine, and tenofovir, as monotherapies and combination therapies, in

treatment-naive individuals. Databases were searched for randomized controlled

trials of the first 12 months of therapy in hepatitis B e antigen

(HBeAg)-positive and/or HBeAg-negative patients with CHB published in English

before October 31, 2009. Bayesian mixed treatment comparisons were used to

calculate the odds ratios, including 95% credible intervals and predicted

probabilities of surrogate outcomes to determine the relative effects of each

treatment.

Results

In HBeAg-positive patients, tenofovir was most effective in inducing

undetectable levels of HBV DNA (predicted probability, 88%), normalization of

alanine aminotransferase (ALT) levels (66%), HBeAg seroconversion (20%), and

hepatitis B surface antigen loss (5%); it ranked third in histologic improvement

of the liver (53%). Entecavir was most effective in improving liver histology

(56%), second for inducing undetectable levels of HBV DNA (61%) and

normalization of ALT levels (70%), and third in loss of hepatitis B surface

antigen (1%). In HBeAg-negative patients, tenofovir was the most effective in

inducing undetectable levels of HBV DNA (94%) and improving liver histology

(65%); it ranked second for normalization of ALT levels (73%).

Conclusions

In the first year of treatment for CHB, tenofovir and entecavir are the most

potent oral antiviral agents for HBeAg-positive patients; tenofovir is most

effective for HBeAg-negative patients.

View this article's video abstract at www.gastrojournal.org

Conflicts of interest These authors disclose the following: Ms Woo is supported

by the Canadian Liver Foundation (graduate studentship); Dr Sherman reported

honoraria (<$10,000 each) for consulting to and speaking on behalf of Gilead,

Bristol-Myers Squibb, Glaxo, Hoffmann-LaRoche, and compensation for being an

expert witness (<$2000); Dr Wong conducts educational rounds that are sponsored

by Axcan, Bristol Myers Squibb, Gilead, Novartis, Roche, and Schering-Plough,

whose content is not related to the subject area; Dr Einarson has received

consulting fees and grant support from Biogen, Amgen, GlaxoKline,

Schering–Plough, Hoffmann–La Roche, Novartis, and Bristol–Meyers Squibb; Dr

Heathcote has received consulting fees and/or grant support from Axcan, Gilead

Sciences, GlaxoKline, Debio, Schering–Plough, Vertex Tibotec, Boehringer

Ingelheim, Bristol–Myers Squibb, and Hoffmann–La Roche; Dr Krahn has received a

grant to fund this study from Gilead Sciences. The remaining authors disclose no

conflicts.

Funding This study was supported by Gilead Sciences. The design and conduct of

the study; collection, management, analysis, and interpretation of the data; and

preparation, review, and approval of the manuscript were performed independently

of Gilead Sciences.None of the funding organizations or sponsors had any role in

the design and conduct of the study; the collection, management, analysis, or

interpretation of the data; or the preparation, review, or approval of the

manuscript.

PII: S0016-5085(10)00901-7

doi:10.1053/j.gastro.2010.06.042

© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.