Sequential therapy with adefovir dipivoxil and pegylated Interferon Alfa-2a for HBeAg-negative patients

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2010.01332.x/abstract

Sequential therapy with adefovir dipivoxil and pegylated Interferon Alfa-2a for

HBeAg-negative patients

R. Moucari1,2,3, N. Boyer1,2,3, M.-P. Ripault1,2,3, C. Castelnau1,2,3, V.

Mackiewicz4, A. Dauvergne5, D. Valla1,2,3, M. Vidaud5, M.-H. N. Chanoine4, P.

Marcellin1,2,3

Article first published online: 17 MAY 2010

DOI: 10.1111/j.1365-2893.2010.01332.x

© 2010 Blackwell Publishing Ltd

Issue

Financial Support: None Potential Conflict of Interest: P. Marcellin advises, is

a consultant for, and is on the speakers’ bureau of Roche, Schering-Plough,

Gilead, Bristol-Myers Squibb, GlaxoKline, and Idenix-Novartis. He is a

consultant for and advises Vertex, Valeant, Human Genome Sciences, Cythesis,

Intermune, Wyeth, and Tibotec.

Journal of Viral Hepatitis

Volume 18, Issue 8, pages 580–586, August 2011

Summary.  To assess the impact of sequential therapy with adefovir dipivoxil

(ADV) and pegylated interferon alfa-2a (PEG-IFN) on virological (serum HBV-DNA)

and serological (serum HBsAg) response in 20 consecutive HBeAg-negative

patients. Patients received ADV for 20 weeks, then ADV and PEG-IFN for 4 weeks

and lastly PEG-IFN for 44 weeks. Serum HBV-DNA and HBsAg were assessed at

baseline, during therapy (weeks 20, 44 and 68) and follow-up (weeks 92 and 116).

Sustained virological response (SVR) was defined as serum HBV-DNA <10 000

copies/mL (partial) or <70 copies/mL (complete) 24 weeks after stopping

treatment. A serological response was defined as a serum HBsAg decrease ≥1

log10IU/mL at the end of treatment. Baseline median serum HBV-DNA and HBsAg

levels were 7.6 log10copies/mL and 3.8 log10IU/mL, respectively. Ten patients

(50%) achieved SVR, six of them had partial response and four complete response.

Four patients (20%) achieved serological response. Complete SVRs showed a major

and steep decline in HBsAg level with a median decrease of 0.5, 1.6 and 2.0

log10IU/mL at treatment week 20, 44 and 68, respectively. Partial SVRs showed a

slight and slow decline in serum HBsAg level (0.1, 0.4, and 0.6 log IU/mL at

weeks 20, 44 and 68, respectively). On-treatment serum HBsAg decrease had a high

accuracy to predict SVR (AUROC = 0.88). Our results suggest that sequential

therapy might be an interesting strategy for HBeAg-negative patients. Serum

HBsAg kinetics seem to be an accurate tool to predict SVR. Large clinical trials

are needed to explore this strategy with more potent analogues.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2010.01332.x/abstract

Sequential therapy with adefovir dipivoxil and pegylated Interferon Alfa-2a for

HBeAg-negative patients

R. Moucari1,2,3, N. Boyer1,2,3, M.-P. Ripault1,2,3, C. Castelnau1,2,3, V.

Mackiewicz4, A. Dauvergne5, D. Valla1,2,3, M. Vidaud5, M.-H. N. Chanoine4, P.

Marcellin1,2,3

Article first published online: 17 MAY 2010

DOI: 10.1111/j.1365-2893.2010.01332.x

© 2010 Blackwell Publishing Ltd

Issue

Financial Support: None Potential Conflict of Interest: P. Marcellin advises, is

a consultant for, and is on the speakers’ bureau of Roche, Schering-Plough,

Gilead, Bristol-Myers Squibb, GlaxoKline, and Idenix-Novartis. He is a

consultant for and advises Vertex, Valeant, Human Genome Sciences, Cythesis,

Intermune, Wyeth, and Tibotec.

Journal of Viral Hepatitis

Volume 18, Issue 8, pages 580–586, August 2011

Summary.  To assess the impact of sequential therapy with adefovir dipivoxil

(ADV) and pegylated interferon alfa-2a (PEG-IFN) on virological (serum HBV-DNA)

and serological (serum HBsAg) response in 20 consecutive HBeAg-negative

patients. Patients received ADV for 20 weeks, then ADV and PEG-IFN for 4 weeks

and lastly PEG-IFN for 44 weeks. Serum HBV-DNA and HBsAg were assessed at

baseline, during therapy (weeks 20, 44 and 68) and follow-up (weeks 92 and 116).

Sustained virological response (SVR) was defined as serum HBV-DNA <10 000

copies/mL (partial) or <70 copies/mL (complete) 24 weeks after stopping

treatment. A serological response was defined as a serum HBsAg decrease ≥1

log10IU/mL at the end of treatment. Baseline median serum HBV-DNA and HBsAg

levels were 7.6 log10copies/mL and 3.8 log10IU/mL, respectively. Ten patients

(50%) achieved SVR, six of them had partial response and four complete response.

Four patients (20%) achieved serological response. Complete SVRs showed a major

and steep decline in HBsAg level with a median decrease of 0.5, 1.6 and 2.0

log10IU/mL at treatment week 20, 44 and 68, respectively. Partial SVRs showed a

slight and slow decline in serum HBsAg level (0.1, 0.4, and 0.6 log IU/mL at

weeks 20, 44 and 68, respectively). On-treatment serum HBsAg decrease had a high

accuracy to predict SVR (AUROC = 0.88). Our results suggest that sequential

therapy might be an interesting strategy for HBeAg-negative patients. Serum

HBsAg kinetics seem to be an accurate tool to predict SVR. Large clinical trials

are needed to explore this strategy with more potent analogues.