Retrospective Study Finds HBsAg

Kinetics Differ During Treatment

With Peginterferon vs Entecavir
Slideset on:
Reijnders JG, Rijckborst V, Sonneveld MJ, et al.
Kinetics of hepatitis B surface antigen differ
between treatment with peginterferon and
entecavir. J Hepatol. 2011;54:449-454.

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HBsAg Kinetics During Treatment With Peginterferon vs Entecavir
clinicaloptions.com/hepatitis

Background and Rationale

 HBV currently is an incurable disease with available therapies
 Persistence of cccDNA in liver thought to prevent HBV cure
– Clearance of HBsAg from serum approximates clinical cure or the best
viral control and associated with improved survival
 Levels of serum HBsAg crudely reflect levels of hepatic cccDNA and
this correlation is better in HBeAg-positive vs HBeAg-negative
patients[1-3]
 Anti-HBV therapies can reduce serum HBsAg during treatment
– HBsAg quantification during therapy may allow identification of sustained
treatment responders[4]
 Current study assessed quantitative serum HBsAg levels in HBeAg-
positive and HBeAg-negative patients with chronic hepatitis B
receiving treatment with pegIFN or ETV monotherapy[5]
1. Werle-Lapostolle B, et al. Gastroenterology. 2004;126:1750-1758. 2. Wursthorn K, et al. Hepatology.
2006;44:675-684. 3. Chan HL, et al. Clin Gastroenterol Hepatol. 2007;5:1462-1468. 4. Moucari R, et al.
Hepatology. 2009;49:1151-1157. 5. Reijnders JG, et al. J Hepatol. 2011;54:449-454.
HBsAg Kinetics During Treatment With Peginterferon vs Entecavir
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Study Design
 Patients treated with pegIFN and ETV matched 2:1 based
on baseline HBV DNA[1]
– ETV-treated patients treated for ≥ 48 wks at medical center
in Rotterdam, The Netherlands, between January 2005 and
May 2008
– PegIFN-treated patients derived from 2 randomized
controlled trials lasting 48-52 wks[2,3]
 Routine assessments conducted every 12 wks
– Included HBV DNA, ALT, HBeAg, anti-HBe, and HBsAg

1. Reijnders JG, et al. J Hepatol. 2011;54:449-454. 2. Rijckborst V, et al. Am J Gastroenterol.

2010;105:1762-1769. 3. Janssen HL, et al. Lancet. 2005;365:123-129.
 HBsAg Kinetics During Treatment With Peginterferon vs Entecavir
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Main Findings: HBeAg-Positive Patients

100

PegIFN (n = 61)
80 ETV (n = 33)
Outcome at Week 48, %

P < .001
60 P = .18
52 48
P = .007
40 P = .05
34 34
26 P = .09
20 16 P = .29
9 10
9 7
0 0
0
HBV DNA HBeAg HBeAg HBsAg HBsAg ALT
< 400 copies/mL Clearance Seroconversion Clearance Seroconversion Normalization

Reijnders JG, et al. J Hepatol. 2011;54:449-454.

HBsAg Kinetics During Treatment With Peginterferon vs Entecavir
clinicaloptions.com/hepatitis

Main Findings: HBeAg-Positive Patients

 HBsAg decreased markedly from baseline to Wk 48 in both treatment arms
 HBV DNA decline significantly greater with ETV (P < .001)
Mean Decrease From Baseline to Week 48 PegIFN ETV P Value
(n = 61) (n = 33)
HBsAg, log10 IU/mL 0.94 0.38 .15
HBV DNA, log10 copies/mL 2.2 4.5 < .001
 HBsAg decline in ETV-treated patients only occurred in those with ALT > 2 x
ULN at baseline
– Strong HBsAg decline observed in pegIFN-treated patients regardless of baseline
ALT
Treatment Mean Decrease in HBsAg From Baseline to P Value
Week 48 Based on Baseline ALT, log10 IU/mL
ALT ≤ 2 x ULN ALT > 2 x ULN
PegIFN 0.90 0.94 .96
ETV -0.03 1.03 .007
Reijnders JG, et al. J Hepatol. 2011;54:449-454.
HBsAg Kinetics During Treatment With Peginterferon vs Entecavir
clinicaloptions.com/hepatitis

Main Findings: HBeAg-Positive Patients

 Decreases in HBsAg and HBV DNA significantly greater in patients
who cleared HBeAg vs patients who remained HBeAg positive at
Week 48, regardless of whether patients were treated with pegIFN or
ETV
Mean Decrease From Baseline to Week 48 HBeAg No HBeAg P Value
Clearance Clearance
HBsAg, log10 IU/mL
 Overall 1.98 0.36 .006
 PegIFN 1.94 0.43 .017
 ETV 2.29 0.24 .46
HBV DNA, log10 copies/mL
 Overall 4.6 2.6 < .001
 PegIFN 4.6 NR NR
 ETV 4.9 NR NR
Reijnders JG, et al. J Hepatol. 2011;54:449-454.
HBsAg Kinetics During Treatment With Peginterferon vs Entecavir
clinicaloptions.com/hepatitis

Main Findings: HBeAg-Negative Patients

 ETV resulted in significantly higher rate of undetectable HBV DNA and
ALT normalization vs pegIFN
 No patients treated with either pegIFN or ETV cleared HBsAg
100
P = .001
84 P = .001
Outcome at Week 48, %

80
73

60
52
PegIFN(n = 69)
41
40 ETV (n = 37)

20

0
HBV DNA ALT
< 400 copies/mL Normalization
Reijnders JG, et al. J Hepatol. 2011;54:449-454.
HBsAg Kinetics During Treatment With Peginterferon vs Entecavir
clinicaloptions.com/hepatitis

Main Findings: HBeAg-Negative Patients

 HBsAg decreased significantly from baseline to Week 48 only in pegIFN arm (P
< .001)
– No decrease observed with ETV

 HBV DNA decreased significantly from baseline to Week 48 in both treatment

groups (P < .001 with both therapies), but decline slightly greater with ETV

Mean Decrease From PegIFN ETV P Value

Baseline to Week 48 (n = 69) (n = 37)
HBsAg, log10 IU/mL 0.56 -0.10 < .001
HBV DNA, log10 copies/mL 3.7 4.2 .13
 HBsAg decline independently associated with treatment regimen according to
multivariate analysis (P < .001)
 HBV genotype distribution differences between the study arms were substantial

Reijnders JG, et al. J Hepatol. 2011;54:449-454.

HBsAg Kinetics During Treatment With Peginterferon vs Entecavir
clinicaloptions.com/hepatitis

Summary of Key Conclusions

 In HBeAg-positive patients, HBsAg decline primarily
occurred in patients who cleared HBeAg, regardless of
treatment with pegIFN or ETV monotherapy
– HBsAg decline during ETV only observed among patients
with baseline ALT > 2 x ULN
– HBsAg decline during pegIFN occurred at same magnitude
regardless of baseline ALT
 In HBeAg-negative patients, significant HBsAg decline
observed with pegIFN monotherapy but not with ETV
monotherapy
– No other factors associated with HBsAg decline
Reijnders JG, et al. J Hepatol. 2011;54:449-454.