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Sustained Virologic Response in Prior Null Responders to Peginterferon/Ribavirin (PR) After Retreatment With Boceprevir + PR: The PROVIDE Study
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Reported by Jules Levin
HEPDART- Frontiers in Drug Development for Viral Hepatitis December 4 - 8, 2011
Koloa, Hawaii
I. Jacobson,1 J. Vierling,2 S. Flamm,3 S. Gordon,4 E. Lawitz,5 J.-P. Bronowicki,6 M. Davis,7 E. Yoshida,8 L. Pedicone,9 W. Deng,9 M. Treitel,9 C. Brass,9 J. Albrecht,9 and F. Poordad10
1Weill Cornell Medical College, New York, NY; 2Baylor College of Medicine, Houston, TX; 3Northwestern Feinberg School of Medicine, Chicago, IL; 4Henry Ford Hospital, Detroit, MI; 5Alamo Medical Research, San Antonio, TX; 6University Henri Poincare of Nancy, Vandoeuvre-lès-Nancy, France; 7South Florida Center of Gastroenterology, Wellington, FL; 8University of British Columbia and Vancouver General Hospital, Vancouver, BC, Canada; 9Merck, Whitehouse Station, NJ; 10Cedars-Sinai Medical Center, Los Angeles, CA
ABSTRACT
BACKGROUND: Combination therapy with boceprevir (BOC), an NS3 protease inhibitor, and peginterferon alfa-2b + ribavirin (PR) vs PR alone has been studied in adults chronically infected with hepatitis C virus (HCV) genotype 1 who were previously untreated (SPRINT-2) or had failed prior PR treatment (RESPOND-2). Patients in the PR control arms of these studies who did not achieve sustained virologic response (SVR) were eligible to enroll in the PROVIDE study and receive BOC + PR. We examined the efficacy of BOC + PR in the subset of patients in PROVIDE who were PR null responders in the previous study (<2 log10 decline in HCV RNA at treatment week 12).
METHODS: BOC (800 mg TID with food) was given with P 1.5 mg/kg/week subcutaneously and weight-based R (600-1400 mg/day) BID for up to 44 weeks. If >2 weeks had elapsed since end of treatment in the previous study, PR was given for 4 weeks before starting BOC+PR. Undetectable HCV RNA was defined as below the limit of detection (LLD = 9.3 IU/mL; Roche TaqMan).
RESULTS: 48 prior null responders from SPRINT-2 or RESPOND-2 enrolled in the PROVIDE study: 65% were male, 69% were white, mean age was 51 years (range, 25-66 years), and mean body mass index was 26.8 kg/m2. Baseline viral load was >800,000 IU/mL in 88% (mean log10 baseline viral load of 6.5); Metavir fibrosis scores were F3/4 in 8% of patients. 65% had subtype 1a and 35% had subtype 1b. 45/48 initiated BOC treatment and 42 completed follow-up; 2 are still on treatment and 1 in early follow-up. The proportion of patients with undetectable HCV RNA at various time points is shown below. Following a null response to prior PR therapy, 38% achieved SVR (27% of black patients, 42% of non-black patients and 41% genotype 1a) with BOC + PR.
CONCLUSIONS: When retreated with BOC + PR, 38% of prior PR null responders achieved SVR. This SVR rate in prior null responders was comparable to the SVR rate (33%) observed in poorly IFN responsive patients (<1 log10 decline after 4-week PR lead-in) treated in the SPRINT-2 and RESPOND-2 studies, for the combined BOC groups.
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