Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics

Meta-analysis of 5 trials

John M. Vierling, Stefan Zeuzem, Fred Poordad, Jean Pierre Bronowicki, Michael P. Manns, Bruce R. Bacon, Rafael Esteban, Steven L. Flamm, Paul Y. Kwo, Lisa D. Pedicone, Weiping Deng, Frank J. Dutko, Mark J. Dinubile, Kenneth J. Koury, Frans A. Helmond, Janice Wahl, Savino Bruno

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background & Aims 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 10 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.

Original languageEnglish
Pages (from-to)200-209
Number of pages10
JournalJournal of Hepatology
Volume61
Issue number2
DOIs
Publication statusPublished - 2014

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Ribavirin
Meta-Analysis
Safety
RNA
Logistic Models
Anemia
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
Sustained Virologic Response
Thrombocytopenia
Diarrhea
Sepsis
Therapeutics
Clinical Trials
Confidence Intervals
Liver

Keywords

  • Chronic HCV
  • Cirrhosis
  • Hepatitis C

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics : Meta-analysis of 5 trials. / Vierling, John M.; Zeuzem, Stefan; Poordad, Fred; Bronowicki, Jean Pierre; Manns, Michael P.; Bacon, Bruce R.; Esteban, Rafael; Flamm, Steven L.; Kwo, Paul Y.; Pedicone, Lisa D.; Deng, Weiping; Dutko, Frank J.; Dinubile, Mark J.; Koury, Kenneth J.; Helmond, Frans A.; Wahl, Janice; Bruno, Savino.

In: Journal of Hepatology, Vol. 61, No. 2, 2014, p. 200-209.

Research output: Contribution to journalArticle

Vierling, JM, Zeuzem, S, Poordad, F, Bronowicki, JP, Manns, MP, Bacon, BR, Esteban, R, Flamm, SL, Kwo, PY, Pedicone, LD, Deng, W, Dutko, FJ, Dinubile, MJ, Koury, KJ, Helmond, FA, Wahl, J & Bruno, S 2014, 'Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics: Meta-analysis of 5 trials', Journal of Hepatology, vol. 61, no. 2, pp. 200-209. https://doi.org/10.1016/j.jhep.2014.03.022
Vierling, John M. ; Zeuzem, Stefan ; Poordad, Fred ; Bronowicki, Jean Pierre ; Manns, Michael P. ; Bacon, Bruce R. ; Esteban, Rafael ; Flamm, Steven L. ; Kwo, Paul Y. ; Pedicone, Lisa D. ; Deng, Weiping ; Dutko, Frank J. ; Dinubile, Mark J. ; Koury, Kenneth J. ; Helmond, Frans A. ; Wahl, Janice ; Bruno, Savino. / Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics : Meta-analysis of 5 trials. In: Journal of Hepatology. 2014 ; Vol. 61, No. 2. pp. 200-209.
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abstract = "Background & Aims 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 10 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.",
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T1 - Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics

T2 - Meta-analysis of 5 trials

AU - Vierling, John M.

AU - Zeuzem, Stefan

AU - Poordad, Fred

AU - Bronowicki, Jean Pierre

AU - Manns, Michael P.

AU - Bacon, Bruce R.

AU - Esteban, Rafael

AU - Flamm, Steven L.

AU - Kwo, Paul Y.

AU - Pedicone, Lisa D.

AU - Deng, Weiping

AU - Dutko, Frank J.

AU - Dinubile, Mark J.

AU - Koury, Kenneth J.

AU - Helmond, Frans A.

AU - Wahl, Janice

AU - Bruno, Savino

PY - 2014

Y1 - 2014

N2 - Background & Aims 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 10 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.

AB - Background & Aims 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 10 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.

KW - Chronic HCV

KW - Cirrhosis

KW - Hepatitis C

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