reijnders jhepatol 2010 slides

8/6/2019 Reijnders JHepatol 2010 Slides

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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.

Retrospective Study Finds HBsAg

Kinetics Differ During TreatmentWith Peginterferon vs Entecavir

This program is supported by educational grants from


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clinicaloptions.com/hepatitis

HBsAg Kinetics During Treatment With Peginterferon vs Entecavir

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 bestviral control and associated with improved survival

Levels of serum HBsAg crudely reflect levels of hepatic cccDNA andthis correlation is better in HBeAg-positive vs HBeAg-negativepatients[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 Breceiving 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.


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Study Design

Patients treated with pegIFN and ETV matched 2:1 basedon baseline HBV DNA[1]

ETV-treated patients treated for 48 wks at medical center

in Rotterdam, The Netherlands, between January 2005 andMay 2008

PegIFN-treated patients derived from 2 randomizedcontrolled 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.


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Main Findings: HBeAg-Positive Patients

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

16

52

0

20

40

60

80

HBV DNA< 400 copies/mL

HBeAgSeroconversion

Outcome

atWeek

48,%

100

PegIFN (n = 61)

ETV (n = 33)

HBeAgClearance

HBsAgClearance

34

9

26

910

0

P< .001

P= .007

P= .05

P= .09

70

P= .29

34

48

P= .18

HBsAgSeroconversion

ALTNormalization


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HBsAg decreased markedly from baseline to Wk 48 in both treatment arms

HBV DNA decline significantly greater with ETV (P< .001)

HBsAg decline in ETV-treated patients only occurred in those with ALT > 2 xULN at baseline

Strong HBsAg decline observed in pegIFN-treated patients regardless of baseline

ALT

Mean Decrease From Baseline to Week 48 PegIFN(n = 61)

ETV(n = 33)

PValue

HBsAg, log10 IU/mL 0.94 0.38 .15

HBV DNA, log10 copies/mL 2.2 4.5 < .001

Treatment Mean Decrease in HBsAg From Baseline toWeek 48 Based on Baseline ALT, log10 IU/mL

PValue

ALT 2 x ULN ALT > 2 x ULN

PegIFN 0.90 0.94 .96

ETV -0.03 1.03 .007


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Decreases in HBsAg and HBV DNA significantly greater in patientswho cleared HBeAg vs patients who remained HBeAg positive atWeek 48, regardless of whether patients were treated with pegIFN orETV

Mean Decrease From Baseline to Week 48 HBeAgClearance

No HBeAgClearance

PValue

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


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Main Findings: HBeAg-Negative Patients

ETV resulted in significantly higher rate of undetectable HBV DNA andALT normalization vs pegIFN

No patients treated with either pegIFN or ETV cleared HBsAg


52

84

0

20

40

60

80

HBV DNA< 400 copies/mL

Outcom

eatWeek48,%

100

PegIFN(n = 69)

ETV (n = 37)

ALTNormalization

P = .001

41

73

P = .001


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

HBsAg decline independently associated with treatment regimen according tomultivariate analysis (P< .001)

HBV genotype distribution differences between the study arms weresubstantial


Mean Decrease FromBaseline to Week 48

PegIFN

(n = 69)

ETV

(n = 37)

PValue

HBsAg, log10 IU/mL 0.56 -0.10 < .001

HBV DNA, log10 copies/mL 3.7 4.2 .13


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Summary of Key Conclusions

In HBeAg-positive patients, HBsAg decline primarilyoccurred in patients who cleared HBeAg, regardless oftreatment with pegIFN or ETV monotherapy

HBsAg decline during ETV only observed among patientswith baseline ALT > 2 x ULN

HBsAg decline during pegIFN occurred at same magnituderegardless of baseline ALT

In HBeAg-negative patients, significant HBsAg declineobserved with pegIFN monotherapy but not with ETVmonotherapy

No other factors associated with HBsAg decline


reijnders jhepatol 2010 slides

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