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Case study. 36 year old HCV+ woman, Risk factor: occasional IVDU 15 years ago First treatment with PEG-IFN/RBV in 2002 only qualitative PCR available : positive at W12 and W24 Treatment stopped after 24 weeks Weight: 65 kg, BMI: 23 No comorbidity, no medications

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36 year old HCV+ woman, Risk factor: occasional IVDU 15 years ago

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36 year old hcv woman risk factor occasional ivdu 15 years ago

Case study

  • 36 year old HCV+ woman,

  • Risk factor: occasional IVDU 15 years ago

  • First treatment with PEG-IFN/RBV in 2002

    • only qualitative PCR available : positive at W12 and W24

    • Treatment stopped after 24 weeks

  • Weight: 65 kg, BMI: 23

  • No comorbidity, no medications

  • Genotype 1a, viral load 6.1 log10

  • Fibroscan: 7.5 KPa

  • Fibrotest: 0.47 (Fibrosis  F1-F2)


Case study

Case study

  • She complains about fatigue

  • She wants to be treated because of this fatigue.

  • No biological or clinical contraindication for the treatment


Would you treat this patient

Would you treat this patient ?

  • No,

    • because of no significant fibrosis

    • Would wait 2d wave PI

  • Yes,

    • because she is really motivated


Would you perform an il28b genotyping in this patient

Would you perform an IL28B genotyping in this patient ?

  • Yes,

    • because the IL28B polymorphism can influence the treatment strategy

  • No


36 year old hcv woman risk factor occasional ivdu 15 years ago

Boceprevir in treatment experienced patients:

SVR rates by IL28B genotype

% SVR

6

13

22

28

17

22

5

29

38

62

48

66

5

10

6

11

13

18

Poordad F, et al. J Hepatol 2011;54(Suppl.):S6


Telaprevir in treatment experienced patients svr rates by il28b genotype and prior response

Telaprevir in treatment experienced patients: SVR Rates by IL28B Genotype and Prior Response

TT

TT

TT

CC

CT

CC

CT

CC

CT

n/N=

4/12

100/117

3/10

5/8

1/5

2/10

10/14

4/10

27/92

1/15

51/58

6/30

29/34

33/57

0/5

1/18

10/32

Prior relapsers

Prior partial responders

Prior null responders

Pooled T12/PR48 (n=134)

Pbo/PR48 (n=33)

Pooled T12/PR48 (n=209)

Pbo/PR48 (n=52)

Pooled T12/PR48 (n=79)

Pbo/PR48 (n=20)

Patients achieving SVR (%)

n/a

Younossi Z et al. Gastroenterology 2011;


Impact of il28b polymorphisms on svr in na ve patients

Impact of IL28B polymorphisms on SVR in naïve patients

CC

CT

TT

CC

CT

TT

100

100

90

82

80

78

80

73

80

71

71

65

64

59

55

60

60

RVS (%)

RVS (%)

40

40

28

27

25

23

20

20

0

0

PR4820/80

T12PR 48/68

PR4835/55

T12PR 45/50

PR486/26

T12PR16/22

PR48

50/64

BOC RGT

63/77

BOC44/PR48 44/55

PR48

33/116

BOC RGT

67/103

BOC44/PR48 82/115

PR48

10/37

BOC RGT

23/42

n/N=

BOC44/PR48 26/44

n/N=

Poordad F, et al. J Hepatol 2011;54(Suppl.):S6

Jacobson IM, et al. J Hepatol 2011;54(Suppl.):S542


36 year old hcv woman risk factor occasional ivdu 15 years ago

Impact of IL28B polymorphisms on SVR in naïve patient

CC

CT

TT

CC

CT

TT

100

100

90

82

80

78

80

73

80

71

71

65

64

59

55

60

60

RVS (%)

RVS (%)

40

40

28

27

25

23

20

20

89 % of CC patients

treated with BOC/PR

were eligible for shorter

therapy

80 % of CC patients

treated with BOC/PR

were eligible for shorter

therapy

0

0

PR4820/80

T12PR 48/68

PR4835/55

T12PR 45/50

PR486/26

T12PR16/22

PR48

50/64

BOC RGT

63/77

BOC44/PR48 44/55

PR48

33/116

BOC RGT

67/103

BOC44/PR48 82/115

PR48

10/37

BOC RGT

23/42

n/N=

BOC44/PR48 26/44

n/N=

Poordad F, et al. J Hepatol 2011;54(Suppl.):S6

Jacobson IM, et al. J Hepatol 2011;54(Suppl.):S542


Svr in patients with a favorable il28b polymorphism and a rvr rs8099917

SVR in patients with a favorable IL28B polymorphism and a RVR (rs8099917)

NS

p <0.001

99

97

95

100

24 week.

80

70

48 week.

60

SVR in patients with RVR (%)

40

20

0

IL28B rs 8099917 TTVL ≥ 600,000 IU/mL

IL28B rs 8099917 TTVL < 600,000 IU/mL

Liu CH, AASLD 2011, # 414


Would you propose a lead in in this patient

Would you propose a lead-in in this patient ?

  • Yes, regardless the PI

    • because it will help to define the responsiveness to interferon of this patient

  • Yes but only in case of BOC prescription


Case study1

Case study

  • Day 1: start of antiviral therapy

    • Peginterferon -2b 1.5 ug/kg/week

    • Ribavirin: 300 mg BID

  • Week 4:

    • Side effect: fatigue

    • Viral load: 5.2 log10 (vs 6.1 log10 at D1)


Will you add a protease inhibitor

Will you add a protease inhibitor ?

  • No, because of <1 log10 decline.

    • Probability of SVR is very low.

    • Probability of resistance very high.

  • Yes, despite <1 log10 decline.

    • Probability of SVR remains significant


36 year old hcv woman risk factor occasional ivdu 15 years ago

100

100

79

73

80

80

60

60

SVR (%)

SVR (%)

34

33

40

40

25

20

20

0

17

0

80

15

90

15

_

_

_

_

_

_

0

0

67

12

110

46

114

44

PR48

BOC RGT

BOC/PR48

PR48

BOC RGT

BOC/PR48

SVR according to the response during the lead –in: boceprevir

<1 log10 HCV RNA reduction at Week 4

≥1 log10 HCV RNA reduction at Week 4

Bacon BR., et al. N Engl J Med 2011; 364:1207-1217.


Predictive value of week 4 response in prior relapsers partial and null responders

Predictive Value of Week 4 Response in Prior Relapsers, Partial and Null Responders

Prior relapsers

Prior null responders

Prior partial responders

Patients achieving SVR (%)

≥1 log10 HCV RNA reduction at Week 4

<1 log10 HCV RNA reduction at Week 4

Prior treatment response provides a more granular prediction of SVRthan < or ≥ 1 log response after 4 weeks of Peg/RBV lead-in phase

Lawitz EJ et al. Gastroenterology 2011


Lead in predicts svr and resistance

Lead-in Predicts SVR and Resistance

  • Boceprevir resistance-associated variants:

  • - ≥1 log10 decline:

    • BOC RGT: 4% (10/232)

    • BOC/PR48: 6% (13/231)

  • - <1 log10 decline:

    • BOC RGT: 52% (49/95)

    • BOC/PR48: 40% (38/94)

Poordad F. N Engl J Med. 2011; 364:1195-1206.

15


36 year old hcv woman risk factor occasional ivdu 15 years ago

↓ viral load 0.9 log in this patient

Variability of Taqman Roche: 0.3-0.5 log


Case study2

Case study

  • Start boceprevir 800 mg/8h (12 pills/day) at Week 4.

  • Week 8.

    • Side effects:  fatigue, dysgeusia, no rash.

    • Hb: 10.5 g/dL (vs 13 g/dL at Day 1).

    • HCV RNA: 3.4 log IU/ml (6.1 log at baseline)

17


What will be your attitude

What will be your attitude ?

  • Stop all treatment

    • Because the probability of SVR = 0

  • Continue the triple therapy and check again the viral response at W12 (W12 stopping rule)

  • Stop BOC and continue PEG-IFN/RBV


Boceprevir svr according to viral response at week 8 in patient poorly responsive to peg ifn

Boceprevir : SVR according to viral response at week 8 in patient poorly responsive to PEG-IFN

17

100

91

83

79

80

60

50

49

48

SVR (%)

38

40

33

30

21

16

20

016

028

044

9

38

628

1020

10

11

223

2370

1531

2329

531

2998

2551

3340

0

0

0

0

< 3

3-4

4-5

> 5

< 3

3-4

4-5

> 5

< 3

3-4

4-5

> 5

Undetectable

Undetectable

Undetectable

RESPOND 2

SPRINT 2

Combined studies

Bacon BR, AASLD 2011, 33 actualisé


Impact of tw12 stopping rules in naive patients

Impact of TW12 stopping rules in naive patients

Jacobson, AASLD 2011, #954


Impact of tw12 stopping rules in treatment experienced patients

Impact of TW12 stopping rules in treatment experienced patients

Jacobson, AASLD 2011, #954


Stop rules

Stop rules

Stop rules for boceprevir

Weeks

0 4 8 12 24 28 36 48

RNA detectable

↕B and PR

RNA ≥100 UI/ml

↕ 3 B and PR

Stop rules for telaprevir

Weeks

0 4 8 12 24 36 48

RNA detectable

↕PR

RNA > 1000 UI/ml

↕ T and PR


Case study3

Case study

  • All the drugs stopped at this point….


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