Debate on Nucs vs INF Singapore 2014
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Transcript of Debate on Nucs vs INF Singapore 2014
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Dont interfere
My first choice is always nucs !
Robert G Gish MDProfessor Consultant
Stanford UniversityMedical Director, Hepatitis B Foundation
Singapore Viral Hepatitis Meeting2014
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Disclosures
Dr Gish has consulting relationships, advisory boards andspeakers bureaus with
BMS Gilead
Roche
Genentech
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Global DeathsCirrhosis and Liver Cancer, 2010
750,000 liver cancer deaths and 1.03 million cirrhosis
deaths
Total deaths increased from 1.25 to 1.75 million per year
An increasing proportion due to liver cancer
HBV associated with 45% of liver cancer & 30% of cirrhosis
HCV and alcohol each cause approximately 25% of deaths
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Discussion:Benefit of Long-term Entecavir Treatment
Cirrhotic patients benefit more to prevent HCC development
Hosaka, et al. Hepatology 2013.
Wong, et al. Hepatology 2013.
Su T-H, et al. AASLD 2013, Washington, DC. Oral 189.
Japan cohort Hong Kong cohort
49 49 41 35 32 29LAM
No. at risk
0 1 3 5
Treatment duration (yr)
Control
ETV
20.9%
38.9%
4.3%7.0%
LAM22.2%
12.2%
50
40
30
20
10
0
0
Cumulativ
edevelopment
ratesofHCC(%)
7985 85
79 7276 65
53 3554 47
17ETVControl
0
0.1
0.2
0.3
0.4
0 12 24 48 6036
Control
ETV
Log-rank test: P=0.036CumulativeprobabilityofHCCin
cirrho
ticpatients
Follow-up duration (months)Patients at riskETV 482 466 365 194 81 20Control 69 65 60 52 45 41
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Figure 1: Serologic and Virological ResponseAccording to ETV Week of Treatment
Ridruejo E, et al. AASLD 2013, Washington, DC. Poster 901.
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Table 3: Predictors of Serologic Response, MultivariateAnalysis by Cox Proportional Hazard Model
Ridruejo E, et al. AASLD 2013, Washington, DC. Poster 901.
Variable HazardRatio
95CI% P value
HBeAgClearance
Gender 1.03 0.41-2.58 0.949
ALT > 5 times ULN 1.85 0.74-4.59 0.182
HBV DNA 7 log10IU/ml 9.40 3.46-25.54
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Figure 2: Cumulative HBV DNA, HBeAg and HBsAg Responsein the Overall Population (Kaplan Meier Survival Estimates)
Ridruejo E, et al. AASLD 2013, Washington, DC. Poster 901.
HBV DNA HBeAg
HBsAg
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Figure 1. Ratio of Undetectable HBVDNAin Patient Groups
Idilman R, et al. AASLD 2013, Washington, DC. Poster 1030.
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LIRA-B Study: PegIFN Lambda Versus PegIFN Alfa inHBsAg-Positive Patients
Lambda was not non-inferior to alfapegIFN for HBeAg seroconversion
End-of-treatment responses between the 2arms were similar
Safety was similar between lambda andalfa arms
Discontinuations due to adverse events(9.6% versus 7.5%)
Serious adverse events (8.8% versus6.0%)
Traditional INF-associated adverse events
Grade 3/4 elevations in liver measureswere more common in lambda (ALTflares), whereas cytopenias were morecommon with alfa (more dosereductions)
0
20
40
60
80
100
Patients(%)
13.8%
44%
52%
3%
Week 72 Outcomes(24 Weeks Post-Dosing)
HBeAgSeroconversionPrimary Outcome
ALTNormalization
Lambda (n=80)
Alfa (n=83)
HBsAgLoss
0%
30.1%
Chan HL, et al. J Hepatol. 2014;60(suppl 1):S48. Abstract O115.
Non-inferiorityCriteria Were
Not Met(Inferior to
pegIFN)
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First 24 weeks: greater earlydeclines in HBV DNA andqHBsAg with Lambda
End of treatment: responsescomparable for Lambda vs alfa
Posttreatment: HBV DNAand qHBeAg responses favoralfa
Quantitative Virologic and Serologic Responses
Chan HL, et al.EASL 2014.
* Significant difference (P< 0.05)
a Roche COBAS TaqMan HPS assay LLOQ 29 IU/mL, LLOD 10 IU/mLb
Abbott Architect assay, linear range, 0.05250 IU/mLcAbbott Architect assay, linear range 0.2256.70 PEIU/mL
Changefrombaseline,
Mean
log10S
E
Lambdaalfa
-1.0
-0.5
0.00 24 48 72qHBsAg
b
Posttreatment
Week0 24 48 72
* *
-2.0
-1.5
-1.0
-0.5
0.0
0 24 48 72qHBeAgc
Posttreatment
Week0 24 48 72
*
-3.5
-2.5
-1.5
-0.5
0 24 48 72HBV DNAa
Week0 24 48 72
* *
Posttreatment
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Nuc real life: Percent of ALT Normalization
Tanwandee T, et al. AASLD 2013, Washington DC, Poster 968.
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Nuc: real life: Percent of Undetectable HBV DNA
Tanwandee T, et al. AASLD 2013, Washington DC, Poster 968.
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Real Life Nucs:Italy: Virological Response* by HBeAg Status
*Undetectable HBV DNA.
Lampertico P, et al. AASLD 2013, Washington, DC. Poster 933.
0
20
40
60
80
100
12
26%Patients%
62%
3624
76%
6
6871 63 52 Patients on f-up
92%
35
48
91%
0
20
40
60
80
100
12
72%
Patients%
88%
3624
95%
6
274274 253 196
97%
114
Months 48
98%
HBeAg positive HBeAg negative
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Figure 2: Cumulative Incidence of HBeAg Seroconversion AmongAsians Versus Non-Asians Treated with ETV or TDF Monotherapy
Jo KJ, et al. AASLD 2013, Washington, DC. Poster 961.
P b bilit f (DNA
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Probability of response (DNA
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Summary
Nucs are superior to interferon
Side effects