title: Boceprevir for chronic HCV genotype 1 infection in patients with prior treatment failure to peginterferon/ribavirin, including prior null response.
abstract: OBJECTIVE
  Boceprevir with peginterferon/ribavirin (BOC/PR) leads to significantly higher sustained virological response (SVR) rates in patients with chronic hepatitis C and partial response or relapse after prior treatment with peginterferon/ribavirin. We studied the efficacy of BOC/PR in patients with prior treatment failure, including those with a null response (<2-log10 decline in HCV RNA), to peginterferon/ribavirin.
  
  
  METHODS
  Patients in the control arms of boceprevir Phase 2/3 studies who did not achieve SVR were re-treated with BOC/PR for up to 44 weeks. Patients enrolling >2 weeks after end-of-treatment in the prior study received PR for 4 weeks before adding boceprevir.
  
  
  RESULTS
  Of 168 patients enrolled, four discontinued from the PR lead-in and 164 received BOC/PR. Baseline viral load was >800,000 IU/ml in 77% of patients; 62% had HCV genotype 1a, and 10% were cirrhotic. In the ITT analysis (all 168 patients), SVR was achieved in 20 (38%) of 52 patients with prior null response, 57 (67%) of 85 with prior partial response, and 27 (93%) of 29 with prior relapse. In the mITT analysis (164 BOC/PR-treated patients), SVR rates were 41% (20/49), 67% (57/85), and 96% (27/28), respectively. SVR was achieved by 48% of patients with <1-log10 decline in HCV-RNA after lead-in and 76% of those with ⩾ 1-log10 decline or undetectable HCV-RNA after lead-in. The most common adverse events were anemia (49%), fatigue (48%), and dysgeusia (35%); 8% of patients discontinued due to adverse events.
  
  
  CONCLUSIONS
  Re-treatment with BOC/PR improved SVR rates in all patient subgroups, including those with prior null response.
authors.affiliation: Baylor College of Medicine, Houston, TX, United States. Electronic address: vierling@bcm.tmc.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Vierling
authors.affiliation: South Florida Center of Gastroenterology, Wellington, FL, United States.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Davis
authors.affiliation: Northwestern Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Steven
authors.initials: S
authors.lastname: Flamm
authors.affiliation: Henry Ford Hospital, Detroit, MI, United States.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
authors.affiliation: The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.affiliation: University of British Columbia and Vancouver General Hospital, Vancouver, Canada.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Yoshida
authors.affiliation: Liver Specialists of Texas, Houston, TX, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Galati
authors.affiliation: Virginia Commonwealth University School of Medicine, Richmond, VA, United States.
authors.forename: Velimir
authors.initials: V
authors.lastname: Luketic
authors.affiliation: Mt. Vernon Endoscopy Center, Alexandria, VA, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McCone
authors.affiliation: Weill Cornell Medical College, New York, NY, United States.
authors.forename: Ira
authors.initials: I
authors.lastname: Jacobson
authors.affiliation: Universite Denis Diderot-Paris, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Duke University School of Medicine, Durham, NC, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muir
authors.affiliation: The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, United States.
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, NJ, United States.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Pedicone
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, NJ, United States.
authors.forename: Janice
authors.initials: J
authors.lastname: Albrecht
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, NJ, United States.
authors.forename: Clifford
authors.initials: C
authors.lastname: Brass
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, NJ, United States.
authors.forename: Anita Y M
authors.initials: AY
authors.lastname: Howe
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, NJ, United States.
authors.forename: Lynn Y
authors.initials: LY
authors.lastname: Colvard
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, NJ, United States.
authors.forename: Frans A
authors.initials: FA
authors.lastname: Helmond
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, NJ, United States.
authors.forename: Weiping
authors.initials: W
authors.lastname: Deng
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, NJ, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Treitel
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, NJ, United States.
authors.forename: Janice
authors.initials: J
authors.lastname: Wahl
authors.affiliation: INSERM U954, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, Vandoeuvre-lès-Nancy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011392:Proline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; C417083:peginterferon alfa-2b
keywords: Boceprevir; Null response; Partial response; Relapse; Sustained virological response