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Clin. Gastroenterol. Hepatol. · Jan 2013
Randomized Controlled TrialBoceprevir with peginterferon alfa-2a-ribavirin is effective for previously treated chronic hepatitis C genotype 1 infection.
- Steven L Flamm, Eric Lawitz, Ira Jacobson, Marc Bourlière, Christophe Hezode, John M Vierling, Bruce R Bacon, Claus Niederau, Morris Sherman, Venkata Goteti, Heather L Sings, Richard O Barnard, John A Howe, Lisa D Pedicone, Margaret H Burroughs, Clifford A Brass, Janice K Albrecht, and Fred Poordad.
- Division of Gastroenterology and Hepatology, Northwestern Feinberg School of Medicine, Chicago, IL 60611, USA. s-flamm@northwestern.edu
- Clin. Gastroenterol. Hepatol. 2013 Jan 1; 11 (1): 81-87.e4; quiz e5.
Background & AimsThe addition of boceprevir to therapy with peginterferon alfa-2b and ribavirin results in significantly higher rates of sustained virologic response (SVR) in previously treated patients with chronic hepatitis C virus (HCV) genotype-1 infection, compared with peginterferon alfa-2b and ribavirin alone. We assessed SVR with boceprevir plus peginterferon alfa-2a-ribavirin (PEG2a/R) in patients with identical study entry criteria.MethodsIn a double-blind, placebo-controlled trial, 201 patients with HCV genotype-1 who had relapsed or not responded to previous therapy were assigned to groups (1:2) and given a 4-week lead-in phase of PEG2a/R, followed by placebo plus PEG2a/R for 44 weeks (PEG2a/R) or boceprevir plus PEG2a/R for 44 weeks (BOC/PEG2a/R). The primary end point was SVR 24 weeks after therapy ended.ResultsThe addition of boceprevir after 4 weeks of lead-in therapy with PEG2a/R significantly increased the rate of SVR from 21% in the PEG2a/R group to 64% in the BOC/PEG2a/R group (P < .0001). Among patients with poor response to interferon therapy (<1-log(10) decline in HCV RNA at week 4), 39% in the BOC/PEG2a/R group had SVRs, compared with none of the patients in the PEG2a/R group. Among patients with good response to interferon (≥1-log(10) decline), 71% in the BOC/PEG2a/R group had SVRs, compared with 25% in the PEG2a/R group. A ≥1-log(10) decline in HCV RNA at treatment week 4 was the strongest independent predictor of SVR, exceeding that of IL-28B genotype. Among 8 patients who began the study with HCV amino acid variants associated with boceprevir resistance, 3 (38%) achieved SVRs. Fifty percent of patients in the BOC/PEG2a/R group developed anemia (hemoglobin <10.0 g/dL), compared with 27% in the PEG2a/R group; 43% vs 21%, respectively, developed neutropenia (neutrophil count <750/mm(3)).ConclusionsThe addition of boceprevir after 4 weeks of lead-in therapy with PEG2a/R caused significantly higher rates of SVR in previously treated patients with chronic HCV genotype-1 infection, compared with patients given only PEG2a/R. ClinicalTrials.gov Identifier: NCT00845065.Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
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