Debate on Nucs vs INF Singapore 2014

8/12/2019 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


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)


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

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Debate on Nucs vs INF Singapore 2014