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Hepatitisweb study
Hepatitisweb study
WINR Study
Flat versus Weight-Based Ribavirin Dosing
Phase 3
Treatment Naïve, Chronic HCV
Jacobson IM, et. al. Hepatology. 2007;46:971-81.
Hepatitisweb study
*Weight-based ribavirin dosing: < 65 kg: 800 mg/d; 65-85 kg: 1000 mg/d; >85-105 kg: 1200 mg/d; >105 kg: 1400 mg/d
Peginterferon alfa-2b + Ribavirin (weight-based or flat-dose) WIN-R Study: Design
• Study- Prospective, randomized, open-label trial
• Subjects- N = 5027 with chronic hepatitis C (4913 analyzed)- Treatment naïve adult patients (Age 18-70)
• Treatment Regimens - Peginterferon alfa-2b: 1.5 µg/kg/wk + Wt-based* Ribavirin: 800-1400 mg/d- Peginterferon alfa-2b: 1.5 µg/kg/wk + Flat-dose Ribavirin: 800 mg/d
• Treatment Duration- Genotypes 1,4,5,6: duration of 48 weeks- Genotypes 2,3: duration of 24 or 48 weeks
• Primary Endpoint- Undetectable serum HCV RNA at end of treatment (ETR) - Undetectable serum HCV RNA 24 weeks after cessation of treatment (SVR)
Source: Jacobson IM, et. al. Hepatology. 2007;46:971-81.
Hepatitisweb study
PEG + Ribavirin (weight-based)
(n = 2111)
PEG + RBV (weight-based)
(n = 333)
48 720Week 24
Source: Jacobson IM, et. al. Hepatology. 2007;46:971-81.
Peginterferon alfa-2b + Ribavirin (weight-based or flat-dose) WIN-R Study: Design
SVR24
GT1-6
Drug DosingPeginterferon alfa-2b: 180 µg once weeklyWeight-based Ribavirin (in 2 divided doses): - 800 mg/d if < 65 kg; 1000 mg/d if 65-85 kg; 1200 mg/d if >85-105 kg; 1400 mg/d if >105 kg Flat-dose Ribavirin (in 2 divided doses): 800 mg/day
GT2, 3
PEG + Ribavirin (flat dose)
(n = 335)
PEG + Ribavirin (flat dose)
(n = 2144)
SVR24
SVR24
SVR24
Hepatitisweb study
Peginterferon alfa-2b + Ribavirin (weight-based or flat-dose) WIN-R Study: Results
SVR 24, by Genotype and Treatment Regimen
Source: Jacobson IM, et. al. Hepatology. 2007;46:971-81.
All GT-1 GT-2,3 0
20
40
60
80
44
34
62
41
29
60
Weight-Based Ribavirin Flat Dose Ribavirin
Pat
ien
ts w
ith
SV
R 2
4 (%
)
938/2121 852/2121 447/1313 377/1305 479/775 462/777
P = .008
P = .005
P = .252
Hepatitisweb study
Weight-Based Ribavirin Flat-Dose Ribavirin 0
20
40
60
80
100
45.2 43.842.038.8
47.3
33.5
65-85 kg
>85-105 kg
>105 kg
Pa
tie
nts
wit
h S
VR
(%
)
P = .973 P = .001
Peginterferon alfa-2b + Ribavirin (weight-based or flat-dose) WIN-R Study: Results
All Treated: SVR24 by Weight Distribution
Source: Jacobson IM, et. al. Hepatology. 2007;46:971-81.
Hepatitisweb study
Peginterferon alfa-2b + Ribavirin (weight-based or flat-dose) WIN-R Study: Results
Genotype 1: SVR24 by Weight Distribution
Source: Jacobson IM, et. al. Hepatology. 2007;46:971-81.
Weight-Based Ribavirin Flat-Dose Ribavirin 0
20
40
60
80
33.831.133.3
28.8
37.3
21.3
65-85 kg
>85-105 kg
>105 kg
Pa
tie
nts
wit
h S
VR
(%
)
P = .569P = .019
Hepatitisweb study
Peginterferon alfa-2b & Weight-based or Flat-dose RibavirinWIN-R Study: Results
Genotypes 2,3: SVR24 by Weight Distribution
Source: Jacobson IM, et. al. Hepatology. 2007;46:971-81.
Weight-Based Ribavirin Flat-Dose Ribavirin 0
20
40
60
80
100
64 6459
5561
55
65-85 kg
>85-105 kg
>105 kg
Pa
tie
nts
wit
h S
VR
(%
) P = .356P = .034
Hepatitisweb study
Peginterferon alfa-2b + Ribavirin (weight-based or flat-dose) WIN-R Study: Results
Sustained Virologic Response (SVR) by Weight Distribution
Source: Jacobson IM, et. al. Hepatology. 2007;46:971-81.
Weight-Based Ribavirin Flat-Dose Ribavirin 0
20
40
60
80
100
13.1 11.7
22.2
9.9
31.3
6.7
African American Genotype 1
65-85 kg
>85-105 kg
>105 kg
Pa
tie
nts
wit
h S
VR
(%
)
P = .036 P = .446
Hepatitisweb study
Peginterferon alfa-2b & Weight-based or Flat-dose RibavirinWIN-R Study: Results
Relapse Rates among Patients who Achieved End-of-Treatment Responses
Source: Jacobson IM, et. al. Hepatology. 2007;46:971-81.
All Treated Genotype 1 Genotypes 2 & 30
5
10
15
20
25
30
35
15.3
23.0
7.0
19
29.6
8.3
Weight-Based Ribavirin Flat-Dose Ribavirin
Re
lap
se
Ra
tes
(%
)
Hepatitisweb studySource: Jacobson IM, et. al. Hepatology. 2007;46:971-81.
Peginterferon alfa-2b & Weight-based or Flat-dose Ribavirin WIN-R Study: Conclusions
Conclusion: “Peginterferon alfa-2b plus weight-based ribavirin is more
effective than flat-dose ribavirin, particularly in genotype 1 patients,
providing equivalent efficacy across all weight groups. Ribavirin 1400
mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3
patients, 24 weeks of treatment with flat-dose ribavirin is adequate; no
evidence of additional benefit of extending treatment to 48 weeks was
demonstrated.”
Hepatitisweb study
Hepatitisweb study
This slide deck is from the University of Washington’s Hepatitis C Online and Hepatitis Web Study projects.
Hepatitis C Online
www.hepatitisc.uw.edu
Hepatitis Web Study
http://depts.washington.edu/hepstudy/
Funded by a grant from the Centers for Disease Control and Prevention.
