Transcript Diapositive 1

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
• 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 ?
• 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 ?
• Yes,
– because the IL28B polymorphism can influence
the treatment strategy
• No
% SVR
Boceprevir in treatment experienced patients:
SVR rates by IL28B genotype
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
Prior partial
responders
Prior null
responders
Pooled T12/PR48 (n=209)
Pooled T12/PR48 (n=79)
Pooled T12/PR48 (n=134)
Pbo/PR48 (n=52)
Pbo/PR48 (n=20)
Pbo/PR48 (n=33)
Patients achieving SVR (%)
Prior
relapsers
n/N=
n/a
51/58
4/12 100/117 6/30
CC
CT
29/34
3/10
TT
5/8
1/5
CC
33/57
2/10
CT
10/14
TT
0/5
4/10
CC
27/92
1/18
CT
10/32
1/15
TT
Younossi Z et al. Gastroenterology 2011;
Impact of IL28B polymorphisms on SVR
in naïve patients
CC
80
78
82
CT
60
28
59
27
CT
90
TT
73
71
64
60
40
25
20
23
20
0
n/N=
CC
80
71
55
40
100
80
65
RVS (%)
TT
RVS (%)
100
0
PR48
BOC BOC44/ PR48 BOC BOC44/ PR48
RGT PR48
RGT PR48
BOC BOC44/
RGT PR48
50/64
63/77 44/55 33/116 67/103 82/115 10/37
23/42
Poordad F, et al. J Hepatol
2011;54(Suppl.):S6
26/44
PR48
T12PR
PR48
T12PR
PR48
T12PR
n/N= 35/55
45/50
20/80
48/68
6/26
16/22
Jacobson IM, et al. J Hepatol 2011;54(Suppl.):S542
Impact of IL28B polymorphisms on SVR in
naïve patient
CC
80
78
82
CT
60
28
59
27
CT
90
TT
73
71
64
60
40
25
20
23
20
0
n/N=
CC
80
71
55
40
100
80
65
RVS (%)
TT
RVS (%)
100
0
PR48
BOC BOC44/ PR48 BOC BOC44/ PR48
RGT PR48
RGT PR48
BOC BOC44/
RGT PR48
50/64
63/77 44/55 33/116 67/103 82/115 10/37
23/42
Poordad F, et al. J Hepatol
2011;54(Suppl.):S6
89 % of CC patients
treated with BOC/PR
were eligible for shorter
therapy
26/44
PR48
T12PR
PR48
T12PR
PR48
T12PR
n/N= 35/55
45/50
20/80
48/68
6/26
16/22
Jacobson IM, et al. J Hepatol 2011;54(Suppl.):S542
80 % of CC patients
treated with BOC/PR
were eligible for shorter
therapy
SVR in patients with a favorable IL28B
polymorphism and a RVR (rs8099917)
SVR in patients with RVR (%)
NS
100
95
p <0.001
99
80
97
70
24 week.
48 week.
60
40
20
0
IL28B rs 8099917 TT
VL < 600,000 IU/mL
IL28B rs 8099917 TT
VL ≥ 600,000 IU/mL
Liu CH, AASLD 2011, # 414
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 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 ?
• 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
SVR according to the response during the
lead –in: boceprevir
≥1 log10 HCV RNA
reduction at Week 4
100
100
80
80
60
33
40
20
0
34
73
79
60
40
25
20
0
0
_
12
PR48
SVR (%)
SVR (%)
<1 log10 HCV RNA
reduction at Week 4
0
15
_
46
BOC RGT
15
_
44
BOC/PR48
17
_
67
PR48
80
90
_
_
110
114
BOC RGT BOC/PR48
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
Prior relapsers
Prior partial responders
Patients achieving SVR (%)
100
Prior null responders
94
80
62
60
59
56
54
40
20
0
15
<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 SVR
than < 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
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
↓ viral load 0.9 log in this patient
Variability of Taqman Roche: 0.3-0.5 log
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 ?
• 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
17
Boceprevir : SVR according to viral response at
week 8 in patient poorly responsive to PEG-IFN
100
RESPOND 2
SPRINT 2
91
83
79
80
SVR (%)
Combined studies
60
50
49
48
38
40
33
30
21
20
0
0
16
0
3
8
< 3 3-4
6
28
10
20
4-5
>5
10
11
0
28
9
0
2
23
< 3 3-4
0
44
23
70
15
31
4-5
>5
23
29
16
0
5
31
29
98
25
51
<3
3-4
4-5
>5
33
40
Bacon BR, AASLD 2011, 33 actualisé
Impact of TW12 stopping rules in
naive patients
Jacobson, AASLD 2011, #954
Impact of TW12 stopping rules in
treatment experienced patients
Jacobson, AASLD 2011, #954
Stop rules
Stop rules for boceprevir
Weeks
0
4
8
12
24
28
RNA ≥100 UI/ml
↕ 3 B and PR
RNA detectable
↕ B and PR
36
48
36
48
Stop rules for telaprevir
Weeks
0
4
8
12
RNA > 1000 UI/ml
↕ T and PR
24
RNA detectable
↕ PR
Case study
• All the drugs stopped at this point….