Systematic Review of the Literature on Comparative Effectiveness of Antiviral Treatments for Chronic Hepatitis B Infection

[Guest guest]

http://www.springerlink.com/content/vj00112122037464/

Journal of General Internal Medicine

DOI: 10.1007/s11606-010-1569-5Online Firstâ„¢

Reviews

Systematic Review of the Literature on Comparative Effectiveness of Antiviral

Treatments for Chronic Hepatitis B Infection

Tatyana A. Shamliyan, R. , Roderick Mac, Aasma Shaukat,

Jian-Min Yuan, L. Kane and J. Wilt

Abstract

OBJECTIVES

To evaluate the comparative effectiveness of antiviral drugs in adults with

chronic hepatitis B monoinfection for evidence-based decision-making.

METHODS

A systematic review of randomized controlled clinical trials (RCTs) published in

English. Results after interferon and nucleos(t)ides analog therapies were

synthesized with random-effects meta-analyses and number needed to treat (NNT).

RESULTS

Despite sustained improvements in selected biomarkers, no one drug regimen

improved all intermediate outcomes. In 16 underpowered RCTs, drug treatments did

not reduce mortality, liver cancer, or cirrhosis. Sustained HBV DNA clearance

was achieved in one patient when two were treated with adefovir (NNT from 1

RCT = 2 95%CI 1;2) or interferon alfa-2b (NNT from 2 RCTs = 2 95%CI

2;4), 13 with lamivudine (NNT from 1 RCT = 13 95%CI 7;1000), and 11 with

peginterferon alfa-2a vs. lamivudine (NNT from 1 RCT = 11 95%CI 7;25).

Sustained HBeAg seroconversion was achieved in one patient when eight were

treated with interferon alfa-2b (NNT from 2 RCTs = 8 95%CI 5;33) or

10—with peginterferon alfa-2b vs. interferon alfa-2b (NNT from 1 RCT = 10

95%CI 5;1000). Greater benefits and safety after entecavir vs. lamivudine or

pegylated interferon alfa-2b vs. interferon alfa-2b require future investigation

of clinical outcomes. Adverse events were common and more frequent after

interferon. Treatment utilization for adverse effects is unknown.

CONCLUSIONS

Individual clinical decisions should rely on comparative effectiveness and

absolute rates of intermediate outcomes and adverse events. Future research

should clarify the relationship of intermediate and clinical outcomes and

cost-effectiveness of drugs for evidence-based policy and clinical decisions.

Corporate names, city, and state of manufacturers of brand-name materials STATA

software (The Statistics/Data Analysis StataCorp. Stata statistical software:

Release 9.2. College Station, Texas, USA)

Adefovir (Hepsera, Gilead Sciences, City, California)

Entecavir (Baraclude, Bristol-Myers Squibb, New York)

Interferon Alfa 2b (Intron A, Schering-Plough, Milan, Italy)

Interferon Alfa 2b (Intron A, Schering Plough, Kenilworth, New Jersey)

Interferon Alfa 2b (Intron A, Shering-Plough, Athens, Greece)

Interferon Alfa 2b (Intron A, Scherag, South Africa)

Interferon Alfa 2b (Schering-Plough, Shanghai, China)

Interferon Alfa 2b (Intron A, Essex, Switzerland)

Lamivudine (Glaxo Wellcome, Suzhou, China)

Lamivudine (Zeffix, GlaxoKline, Greenford, United Kingdom)

Lamivudine (Epivir-HBV Glaxo-Wellcome Inc, Research Triangle Park, North

Carolina)

Lamivudine (GSK, Athens, Greece)

Lamivudine (Zeffix, GlaxoKline, Middlesex, UK)

Peginterferon alfa-2a (PEGASYS, F. Hoffmann-La Roche Ltd., Basel, Switzerland)

Peginterferon alfa-2b (PegIntron, Schering-Plough Corp., Kenilworth, New Jersey)

Telbivudine Idenix Pharmaceuticals Inc. (Cambridge, Massachusetts)

Tenofovir DF Gilead Sciences

[Guest guest]

http://www.springerlink.com/content/vj00112122037464/

Journal of General Internal Medicine

DOI: 10.1007/s11606-010-1569-5Online Firstâ„¢

Reviews

Systematic Review of the Literature on Comparative Effectiveness of Antiviral

Treatments for Chronic Hepatitis B Infection

Tatyana A. Shamliyan, R. , Roderick Mac, Aasma Shaukat,

Jian-Min Yuan, L. Kane and J. Wilt

Abstract

OBJECTIVES

To evaluate the comparative effectiveness of antiviral drugs in adults with

chronic hepatitis B monoinfection for evidence-based decision-making.

METHODS

A systematic review of randomized controlled clinical trials (RCTs) published in

English. Results after interferon and nucleos(t)ides analog therapies were

synthesized with random-effects meta-analyses and number needed to treat (NNT).

RESULTS

Despite sustained improvements in selected biomarkers, no one drug regimen

improved all intermediate outcomes. In 16 underpowered RCTs, drug treatments did

not reduce mortality, liver cancer, or cirrhosis. Sustained HBV DNA clearance

was achieved in one patient when two were treated with adefovir (NNT from 1

RCT = 2 95%CI 1;2) or interferon alfa-2b (NNT from 2 RCTs = 2 95%CI

2;4), 13 with lamivudine (NNT from 1 RCT = 13 95%CI 7;1000), and 11 with

peginterferon alfa-2a vs. lamivudine (NNT from 1 RCT = 11 95%CI 7;25).

Sustained HBeAg seroconversion was achieved in one patient when eight were

treated with interferon alfa-2b (NNT from 2 RCTs = 8 95%CI 5;33) or

10—with peginterferon alfa-2b vs. interferon alfa-2b (NNT from 1 RCT = 10

95%CI 5;1000). Greater benefits and safety after entecavir vs. lamivudine or

pegylated interferon alfa-2b vs. interferon alfa-2b require future investigation

of clinical outcomes. Adverse events were common and more frequent after

interferon. Treatment utilization for adverse effects is unknown.

CONCLUSIONS

Individual clinical decisions should rely on comparative effectiveness and

absolute rates of intermediate outcomes and adverse events. Future research

should clarify the relationship of intermediate and clinical outcomes and

cost-effectiveness of drugs for evidence-based policy and clinical decisions.

Corporate names, city, and state of manufacturers of brand-name materials STATA

software (The Statistics/Data Analysis StataCorp. Stata statistical software:

Release 9.2. College Station, Texas, USA)

Adefovir (Hepsera, Gilead Sciences, City, California)

Entecavir (Baraclude, Bristol-Myers Squibb, New York)

Interferon Alfa 2b (Intron A, Schering-Plough, Milan, Italy)

Interferon Alfa 2b (Intron A, Schering Plough, Kenilworth, New Jersey)

Interferon Alfa 2b (Intron A, Shering-Plough, Athens, Greece)

Interferon Alfa 2b (Intron A, Scherag, South Africa)

Interferon Alfa 2b (Schering-Plough, Shanghai, China)

Interferon Alfa 2b (Intron A, Essex, Switzerland)

Lamivudine (Glaxo Wellcome, Suzhou, China)

Lamivudine (Zeffix, GlaxoKline, Greenford, United Kingdom)

Lamivudine (Epivir-HBV Glaxo-Wellcome Inc, Research Triangle Park, North

Carolina)

Lamivudine (GSK, Athens, Greece)

Lamivudine (Zeffix, GlaxoKline, Middlesex, UK)

Peginterferon alfa-2a (PEGASYS, F. Hoffmann-La Roche Ltd., Basel, Switzerland)

Peginterferon alfa-2b (PegIntron, Schering-Plough Corp., Kenilworth, New Jersey)

Telbivudine Idenix Pharmaceuticals Inc. (Cambridge, Massachusetts)

Tenofovir DF Gilead Sciences