REPEAT Study: Non-responders to ≥12 weeks' treatment with standard-dose pegylated interferon alfa-2b (PegIntron) plus ribavirin received standard dose of Pegasys + ribavrin or double dose Pegasys + ribavirin
Efficacy and Safety Analysis of the 12-Week Induction Period
Patrick Marcellin
Hopital Beaujon, Clichy,
France
Brief Summary
Rates of early response at 12 weeks: Retreatment with peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) achieved high rates of early response at 12 weeks
--45% with standard dose (180 ug/week)
--62% with induction dose (360 ug/week)
Rtes of early response at 12 weeks for non-responders to pegylated interferon alfa-2b (12KD) with advanced liver disease
38% with standard dose
50% with induction dose
High induction doses of Pegasys (double dose) was tolerated similarly as standard Pegasys dose.
BACKGROUND
Up to half of all patients treated with pegylated interferon alfa-2b (12KD) plus ribavirin fail to achieve an SVR. Treatment options for patients who have failed an initial course of pegylated interferon plus ribavirin combination therapy are currently limited. Initial retreatment studies have suggested a benefit of induction doses and/or prolonged duration of treatment in previous non-responders.
REPEAT study: primary objective:
To investigate efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in patients who did not respond to previous pegylated interferon alfa-2b (12KD) plus ribavirin combination therapy. The study looks at two approaches to therapy:
--High-dose induction during weeks 1-12
(360 mg/week vs 180 mg/week)
--Extended duration of treatment
(72 vs 48 weeks)
*RBV dose is 1000-1200mg day.
Planned interim efficacy and safety analysis:
A prospectively-defined, protocol-planned efficacy and safety analysis was conducted after all patients had been treated for 12 weeks
--All randomized and treated patients were included
--Analysis: Peginterferon alfa-2a 360 mg/week versus 180 mg/week
(Arms A + B vs Arms C + D)
PATIENTS
--Non-responders to ≥12 weeks' treatment with standard-dose pegylated interferon alfa-2b plus ribavirin
--Pegylated interferon alfa-2b plus ribavirin discontinued ≥12 weeks prior to enrollment
--Age ≥18 years
--Detectable HCV RNA (>600 IU/mL) in serum
--Liver biopsy consistent with a diagnosis of chronic hepatitis C
--Compensated liver disease
--Recruited between September 2003 and March 2005
BASELINE CHARACTERISTICS
65% men.
48 yrs old.
BMI, kg/m2: 27.4 - 27.9
Race: 88% Caucasian; 12% Black.
ALT quotient: 0-1 14%-17%
>/= 1: 86-83%
HCV genotype 1: 91%; 2 or 3: 3%
HCV RNA (x 106th IU/mL): 4.9 in 180 ug/wk (n=469); 5.4 in 360 ug/wk (n=473)
Cirrhosis/advanced fibrosis: 28%-25%
Median duration of most recent therapy: 28 weeks
