Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior HBeAg seroconversion rates in HBV genotypes B or C

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1002/hep.24555/abstract

Shorter durations and lower doses of peginterferon alfa-2a are associated with

inferior HBeAg seroconversion rates in HBV genotypes B or C

Y-F Liaw1,*,?, J-D Jia2, HLY Chan3, KH Han4, T Tanwandee5, WL Chuang6, D Tan7,

XY Chen8, E Gane9, T Piratvisuth10, L Chen11, Q Xie12, JJY Sung3, C Wat13, C

Bernaards14, Y Cui15, P Marcellin16DOI: 10.1002/hep.24555

Copyright © 2011 American Association for the Study of Liver Diseases

Issue

Hepatology

Accepted Article (Accepted, unedited articles published online for future

issues)

Abstract

As there is currently a lack of consensus on the most appropriate dose and

duration of peginterferon alfa-2a (PEG-IFNá-2a) therapy in hepatitis B e antigen

(HBeAg)-positive patients, the efficacy and safety of either 24 or 48 weeks'

duration and 90ìg/week or 180ìg/week doses were compared. HBeAg-positive

patients (n=544; 34% genotype B, 51% genotype C) were randomized to receive

PEG-IFNá-2a (2x2 factorial design) for 24 or 48 weeks and at 90 ìg/week or 180

ìg/week and included in the per protocol population. The primary efficacy

endpoint of the non-inferiority study was HBeAg seroconversion 6 months

post-treatment. The prespecified odds ratio (OR) non-inferiority margin was 1.88

with a one-sided significance level of 0.025. The highest rates of HBeAg

seroconversion 6 months post-treatment were in the 180/48 arm (36.2% versus

14.1%-25.8% in the other arms). When the dose and duration arms were pooled, the

OR for non-inferiority of 24 weeks versus 48 weeks was 2.17 (95% confidence

interval [CI] 1.43, 3.31; P= 0.749) and for 90 ìg versus 180 ìg was 1.79 (95% CI

1.18, 2.72; P=0.410). As the upper limit of the 95% CI of the ORs were >1.88, 24

weeks were inferior to 48 weeks and 90ìg/week was inferior to 180ìg/week.

Highest rates of response in the 180/48 arm were achieved by patients with HBsAg

<1500 IU/mL at Week 12 (58%) or Week 24 (57%), whilst patients with HBsAg

>20,000 IU/mL did not respond. Adverse events were typical of those associated

with PEG-IFNá-2a.

Conclusions:

Compared with lower doses and shorter durations, the licensed PEG-IFNá-2a

treatment regimen (180ìg/48 weeks) was the most efficacious and beneficial for

HBeAg-positive patients predominantly infected with HBV genotype B or C.

(HEPATOLOGY 2011.)

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1002/hep.24555/abstract

Shorter durations and lower doses of peginterferon alfa-2a are associated with

inferior HBeAg seroconversion rates in HBV genotypes B or C

Y-F Liaw1,*,?, J-D Jia2, HLY Chan3, KH Han4, T Tanwandee5, WL Chuang6, D Tan7,

XY Chen8, E Gane9, T Piratvisuth10, L Chen11, Q Xie12, JJY Sung3, C Wat13, C

Bernaards14, Y Cui15, P Marcellin16DOI: 10.1002/hep.24555

Copyright © 2011 American Association for the Study of Liver Diseases

Issue

Hepatology

Accepted Article (Accepted, unedited articles published online for future

issues)

Abstract

As there is currently a lack of consensus on the most appropriate dose and

duration of peginterferon alfa-2a (PEG-IFNá-2a) therapy in hepatitis B e antigen

(HBeAg)-positive patients, the efficacy and safety of either 24 or 48 weeks'

duration and 90ìg/week or 180ìg/week doses were compared. HBeAg-positive

patients (n=544; 34% genotype B, 51% genotype C) were randomized to receive

PEG-IFNá-2a (2x2 factorial design) for 24 or 48 weeks and at 90 ìg/week or 180

ìg/week and included in the per protocol population. The primary efficacy

endpoint of the non-inferiority study was HBeAg seroconversion 6 months

post-treatment. The prespecified odds ratio (OR) non-inferiority margin was 1.88

with a one-sided significance level of 0.025. The highest rates of HBeAg

seroconversion 6 months post-treatment were in the 180/48 arm (36.2% versus

14.1%-25.8% in the other arms). When the dose and duration arms were pooled, the

OR for non-inferiority of 24 weeks versus 48 weeks was 2.17 (95% confidence

interval [CI] 1.43, 3.31; P= 0.749) and for 90 ìg versus 180 ìg was 1.79 (95% CI

1.18, 2.72; P=0.410). As the upper limit of the 95% CI of the ORs were >1.88, 24

weeks were inferior to 48 weeks and 90ìg/week was inferior to 180ìg/week.

Highest rates of response in the 180/48 arm were achieved by patients with HBsAg

<1500 IU/mL at Week 12 (58%) or Week 24 (57%), whilst patients with HBsAg

>20,000 IU/mL did not respond. Adverse events were typical of those associated

with PEG-IFNá-2a.

Conclusions:

Compared with lower doses and shorter durations, the licensed PEG-IFNá-2a

treatment regimen (180ìg/48 weeks) was the most efficacious and beneficial for

HBeAg-positive patients predominantly infected with HBV genotype B or C.

(HEPATOLOGY 2011.)