1. Maria Buti,1 Yoav Lurie,2 Natalia G. Zakharova,3 Natalia P. Blokhina,4 Andrzej Horban,5 Gerlinde Teuber,6 Christoph Sarrazin,6 Ligita Balciuniene,7 Saya V. Feinman,8 Rab Faruqi,9 Lisa D. Pedicone,9 and Rafael Esteban1; for the SUCCESS Study Investigators Hepatology Vol. 52, No. 4, October 2010 소화기내과 R2. 신아리 Randomized Trial of Peg IFN alfa-2b & Ribavirin for 48 or 72 Weeks in Patients with HCV Genotype 1 and Slow Virologic Response Journal conference 2010.11.15

2. Standard of care chronic hepatitis C (CHC) genotype 1 (G1) infection - Peginterferon (PEG-IFN) alfa-2a or alfa-2b plus ribavirin (RBV) for 48 wks ; sustained virologic response (SVR) : 40%-52% largely unsatisfactory Several studies suggested that extending therapy to 72 wks may increase SVR rates in selected G1 pts Which HCV G1 patients will benefit from extended Tx is important !! because prolonged treatment is a/w increased adverse events & higher costs. Background - SVR (Sustained Virologic Response) : undetectable HCV RNA at the end of Tx & 24wks f/u - EVR (Early Virologic Resoponse) : <2log10 or loss of HCV RNA at 12 wk Tx - Slow Virologic Response : detectable, but >2log10 loss HCV RNA at 12 wk Tx undetectable HCV RNA at 24 wk Tx - ETR (End of Treatment Response) : undetectable HCV RNA at the end of Tx. - Relapse : undetectable HCV RNA during Tx, but, detectable HCV RNA end of Tx

3. Purpose In patients with HCV Genotype 1, who shows slow virologic response Standard Tx duration : 48 wks Tx Expending Tx duration : 72 wks Tx VS Increase in SVR ? Adverse event ?

4. Study Patients - Inclusion criteria Aged 18-70 years, treatment-naı¨ve Compensated CHC ; anti-HCV (+) & detectable HCV RNA ALT levels above upper limits of normal Liver biopsy performed that histologically confirmed chronic hepatitis - Exclusion criteria Body weight >125 kg Coinfection with hepatitis B virus, HIV, or both Any cause of liver disease other than CHC. Patient evaluation - HCV RNA analysis Central laboratory using quantitative reverse transcriptase polymerase change reaction assay with a lower limit of quantiation of 30 IU/ml At screening, baseline, and Tx weeks 4, 8, 12, 24, 48, and 72 and at week 24 f/u Methods

5. Study Design - Prospective, open-label, randomized, multicenter, international study - 133 centers between December 2004 and May 2008. - Treatment PEG-IFN alfa-2b 1.5 ug/kg/wk + RBV 800-1,400 mg/d according to Bwt Protocol : All pts Tx for 12wk period Further Tx duration according to week 12 HCV RNA levels <2-log decline from baseline Withdrawn from Tx Undetectable HCV RNA (cEVR) Additional 36 wks Tx (Group C, 48wks) Detectable HCV RNA & ≥2-log drop (pEVR) continued to receive same Tx until week 24 - detectable HCV RNA at 24 week Withdrawn from Tx - undetectable HCV RNA at 24 week (=slow responders) randomized to ; Additional 24 wks (Group A, 48wks) Additional 48 wks (Group B, 72wks) Methods

6. Study End Points - Primary end points Compare the percentage of slow responders attaining SVR when longer duration Tx of 72 wks with standard Tx duration of 48 wks in patients with slow virologic response (Group A Vs Group B) - Secondary endpoints End-of-treatment response (ETR, undetectable HCV RNA at the end of Tx) Relapse rates (ETR, but detectable HCV RNA at 24-week f/u) Safety, Tolerability. Methods

7. Results 1)Study Design 2) Patients Demographics 3)Virologic response 4)Variables associated with SVR 5)Adverse Events

8. 1. Study Design

9. 2. Patient Demographics and Diposition

10. 3. Virologic Response

11. 4. Variables associated with SVR Week 8 HCV RNA load

12. 4. Adverse Events

13. Our study suggest that SVR rates were similar among slow responder who received PEG-IFN alfa-2b & RBV for 48 or 72 wks prolonged therapy in slow responders not supported Adverse event were also similar but, rates of adverse event leading to discontinuation were higher for 72wk regimen Standard Tx of HCV genotype-1 : 48-week regimen of PEG-IFN alfa-2b & RBV Conclusion