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Boceprevir for Previously Treated Chronic HCV Genotype 1 Infection
N Engl J Med 2011; 364:1207-1217March 31, 2011

http://www.nejm.org/doi/full/10.1056/NEJMoa1009482?query=TOC


Bruce R. Bacon, M.D., Stuart C. Gordon, M.D., Eric Lawitz, M.D., Patrick Marcellin, M.D., John M. Vierling, M.D., Stefan Zeuzem, M.D., Fred Poordad, M.D., Zachary D. Goodman, M.D., Ph.D., Heather L. Sings, Ph.D., Navdeep Boparai, M.S., Margaret Burroughs, M.D., Clifford A. Brass, M.D., Ph.D., Janice K. Albrecht, Ph.D., and Rafael Esteban, M.D. for the HCV RESPOND-2 Investigators

Background
In patients with chronic infection with hepatitis C virus (HCV) genotype 1 who do not have a sustained response to therapy with peginterferon–ribavirin, outcomes after retreatment are suboptimal. Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3 (NS3) active site, has been suggested as an additional treatment.

Methods
To assess the effect of the combination of boceprevir and peginterferon–ribavirin for retreatment of patients with chronic HCV genotype 1 infection, we randomly assigned patients (in a 1:2:2 ratio) to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (control group) received placebo plus peginterferon–ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon–ribavirin for 32 weeks, and patients with a detectable HCV RNA level at week 8 received placebo plus peginterferon–ribavirin for an additional 12 weeks; and group 3 received boceprevir plus peginterferon–ribavirin for 44 weeks.

Results
A total of 403 patients were treated. The rate of sustained virologic response was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in the control group (21%, P<0.001). Among patients with an undetectable HCV RNA level at week 8, the rate of sustained virologic response was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients with a decrease in the HCV RNA level of less than 1 log10 IU per milliliter at treatment week 4, the rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively. Anemia was significantly more common in the boceprevir groups than in the control group, and erythropoietin was administered in 41 to 46% of boceprevir-treated patients and 21% of controls.

Conclusions
The addition of boceprevir to peginterferon–ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon–ribavirin alone. (Funded by Schering-Plough [now Merck]; HCV RESPOND-2 ClinicalTrials.gov number, NCT00708500.)

The opinions expressed in this report represent the consensus of the authors and do not necessarily reflect the formal position of Merck or other institutions listed as authors' affiliations.

Sponsored by Schering-Plough (now part of Merck).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank all the patients, health care providers, and investigators involved in the study, Dr. Lisa Pedicone of Merck for her helpful advice and invaluable support, and Karyn Davis of Merck for technical assistance.

Source Information
From Saint Louis University School of Medicine, St. Louis (B.R.B.); Henry Ford Hospital, Detroit (S.C.G.); Alamo Medical Research, San Antonio, TX (E.L.); University Paris–Diderot, Hôpital Beaujon, Clichy, France (P.M.); Baylor College of Medicine, Houston (J.M.V.); the Department of Medicine, J.W. Goethe University Hospital, Frankfurt, Germany (S.Z.); Cedars–Sinai Medical Center, Los Angeles (F.P.); Inova Fairfax Hospital and the Betty and Guy Beatty Center for Integrated Research, Falls Church, VA (Z.D.G.); Merck, Sharp & Dohme, Whitehouse Station, NJ (H.L.S., N.B., M.B., C.A.B., J.K.A.); and Hospital General Universitario Vall d'Hebron and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas del Instituto Carlos III, Barcelona (R.E.).

Address reprint requests to Dr. Bacon at the Saint Louis University School of Medicine, 3635 Vista Ave. at Grand Blvd., St. Louis, MO 63110-0250, or at [e-mail].

The Hepatitis C Virus (HCV) RESPOND-2 (Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2) Investigators are listed in the Supplementary Appendix, available at NEJM.org.