duration and dose finding peginterferon alfa-2a + ribavirin
DESCRIPTION
Phase 3. Treatment Naïve, Chronic HCV. Duration and Dose Finding Peginterferon alfa-2a + Ribavirin . Randomized study of low-dose versus weight based ribavirin and 24 versus 48 weeks of therapy. Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55. . - PowerPoint PPT PresentationTRANSCRIPT
Hepatitisweb study
Hepatitisweb study
Duration and Dose Finding Peginterferon alfa-2a + Ribavirin
Phase 3
Treatment Naïve, Chronic HCV
Randomized study of low-dose versus weight based ribavirin and 24 versus 48 weeks of therapy
Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.
Hepatitisweb study
*Ribavirin dose: Ribavirin 1000 mg/day for Wt <75 kg, 1200 mg/day for Wt ≥75 kg
Peginterferon alfa-2a + Ribavirin for Chronic HCVTreatment Duration and Ribavirin Dose
• Study- Randomized, double-blind trial, with 2 x 2 factorial design
• Subjects- N = 1311 with chronic hepatitis C (1284 treated)- Treatment naïve adult patients; 58% genotype 1 - Serum ALT above upper limit of normal x prior 6 months
• Regimens - Peginterferon alfa-2a: 180 µg/wk + Ribavirin: 800 mg/day x 24 wks - Peginterferon alfa-2a: 180 µg/wk + *Ribavirin: 1000-1200 mg/day x 24 wks - Peginterferon alfa-2a: 180 µg/wk + Ribavirin: 800 mg/d x 48 weeks- Peginterferon alfa-2a: 180 µg/wk + *Ribavirin: 1000-1200 mg/day x 48 wks
• Primary Endpoint- Undetectable serum HCV RNA at end of treatment (ETR) - Undetectable serum HCV RNA 24 wks after cessation of treatment (SVR)
Source: Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.
Hepatitisweb study
Peginterferon alfa-2a + Ribavirin (low dose)(n = 214)
Peginterferon alfa-2a + Ribavirin (low dose)(n = 365)
Peginterferon alfa-2a + Ribavirin (weight-based dose)(n = 288)
Peginterferon alfa-2a + Ribavirin (weight-based dose)(n = 444)
48 720 12
Randomize
Week 24
Source: Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.
Peginterferon alfa-2a + Ribavirin for Chronic HCVTreatment Duration and Ribavirin Dose
SVR24
SVR24
SVR24
SVR24
Hepatitisweb study
Genotype 1 Genotypes 2 or 30
20
40
60
80
100
29
84
42
81
41
79
52
80
PEG + RBV (low dose) x 24 weeks PEG + RBV (weight-based dose) x 24 weeks
PEG + RBV (low dose) x 48 weeks PEG + RBV (weight-based dose) x 48 weeks
Genotype
Patie
nts
with
SVR
(%)
Peginterferon alfa-2a + Ribavirin for Chronic HCVTreatment Duration and Ribavirin Dose
SVR24 Rates, by Regimen
Source: Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.
n = 101 n = 118 n = 250 n = 271 n = 96 n = 144 n = 99 n = 153
Hepatitisweb study
All Patients Low Viral Load_x000d_(≤2 mil-
lion)
High Viral Load_x000d_(>2 mil-
lion)
0
20
40
60
80
10084 85 8481 83 8079
88
7480 77
82
Peginterferon + Ribavirin (low dose) x 24 weeks Peginterferon + Ribavirin (weight-based dose) x 24 weeks Peginterferon + Ribavirin (low dose) x 48 weeks Peginterferon + Ribavirin (weight-based dose) x 48 weeks
Patie
nts
with
SVR
(%)
Peginterferon alfa-2a + Ribavirin for Chronic HCVTreatment Duration and Ribavirin Dose
Rates of SVR with Different Peginterferon + Ribavivirn Regimens
Source: Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.
(≤ 2 x 106 copies/ml) (> 2 x 106 copies/ml)
Hepatitisweb studySource: Hadziyannis SJ, et. al. Ann Intern Med. 2004;140:346-55.
Peginterferon alfa-2a + Ribavirin for Chronic HCVTreatment Duration and Ribavirin Dose
Conclusion: “Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require
treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.”
Hepatitisweb study
Hepatitisweb study
This slide deck is from the University of Washington’s Hepatitis C Online and Hepatitis Web Study projects.
Hepatitis C Onlinewww.hepatitisc.uw.edu
Hepatitis Web Studyhttp://depts.washington.edu/hepstudy/
Funded by a grant from the Centers for Disease Control and Prevention.