title: Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics: meta-analysis of 5 trials.
abstract: OBJECTIVE
  HCV-infected cirrhotics may urgently need therapy but are often under-represented in clinical trials resulting in limited data to guide their management. We performed a meta-analysis of well-compensated cirrhotic patients from five Phase 3 trials.
  
  
  METHODS
  Patients received P/R (peginterferon/ribavirin; 4 weeks) followed by BOC (boceprevir)/P/R or P/R for 24, 32, or 44 weeks. Sustained virologic response (SVR) rates were calculated by Metavir score. Multivariate logistic regression (MLR) models identified baseline and on-treatment predictors of SVR. Safety was evaluated by adverse-event (AE) reporting and laboratory monitoring.
  
  
  RESULTS
  Pooled meta-estimates for SVR rates (95% confidence interval) in 212 F4 (cirrhotic) patients were 55% (43, 66) with BOC/P/R vs.17% (0, 41) with P/R. MLR identified 4 predictors of SVR in F3/F4 patients: undetectable HCV-RNA at treatment week (TW) 8; ⩾ 1 log10 decline in HCV-RNA from baseline at TW4; male; and baseline HCV-RNA ⩽ 800,000 IU/ml. SVR rate was 89% (65/73) in F4 patients who were HCV-RNA undetectable at TW8. No F3 (0/5) or F4 (0/17) patients with <3 log10 decline and detectable HCV-RNA at TW8 achieved SVR. Anemia and diarrhea occurred more frequently in cirrhotic than non-cirrhotic patients. Serious AEs, discontinuations due to an AE, interventions to manage anemia, infections, and thrombocytopenia occurred more frequently in cirrhotics with BOC/P/R than P/R. Potential hepatic decompensation and/or sepsis were identified in 2 P/R and 3 BOC/P/R recipients.
  
  
  CONCLUSIONS
  BOC/P/R appears to have a generally favorable benefit-risk profile in compensated cirrhotic patients. SVR rates were particularly high in cirrhotic patients with undetectable HCV-RNA at TW8.
authors.affiliation: Baylor College of Medicine, Houston, TX, USA. Electronic address: vierling@bcm.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Vierling
authors.affiliation: JW Goethe University Hospital, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
authors.affiliation: INSERMU954, CHU de Nancy, Université de Lorraine, Vandoeuvre-lès-Nancy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.affiliation: Medical School of Hannover, Hannover, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Bacon
authors.affiliation: Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
authors.affiliation: Northwestern Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Flamm
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Kwo
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Pedicone
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Deng
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Dutko
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Koury
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Frans A
authors.initials: FA
authors.lastname: Helmond
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Wahl
authors.affiliation: A.O. Fatebenefratelli e Oftalmico, Milan, Italy.
authors.forename: Savino
authors.initials: S
authors.lastname: Bruno
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; 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; C100416:peginterferon alfa-2a
keywords: Chronic HCV; Cirrhosis; Hepatitis C