Boceprevir early-access for advanced-fibrosis/cirrhosis in Asia-Pacific hepatitis C virus genotype 1 non-responders/relapsers

World J Gastroenterol. 2015 Jul 28;21(28):8660-9. doi: 10.3748/wjg.v21.i28.8660.

Abstract

Aim: To examined the efficacy and safety of treatment with boceprevir, PEGylated-interferon and ribavirin (PR) in hepatitis C virus genotype 1 (HCVGT1) PR treatment-failures in Asia.

Methods: The Boceprevir Named-Patient Program provided boceprevir to HCVGT1 PR treatment-failures. Participating physicians were invited to contribute data from their patients: baseline characteristics, on-treatment responses, sustained virological response at week 12 (SVR12), and safety were collected and analysed. Multivariate analysis was performed to determine predictors of response.

Results: 150 patients were enrolled from Australia, Malaysia, Singapore and Thailand (Asians = 86, Caucasians = 63). Overall SVR12 was 61% (Asians = 59.3%, Caucasians = 63.5%). SVR12 was higher in relapsers (78%) compared with non-responders (34%). On-treatment responses predicted SVR, with undetectable HCVRNA at week 4, 8 and 12 leading to SVR12s of 100%, 87%, and 82% respectively, and detectable HCVRNA at week 4, 8 and 12, leading to SVR12s of 58%, 22% and 6% respectively. Asian patients were similar to Caucasian patients with regards to on-treatment responses. Patients with cirrhosis (n = 69) also behaved in the same manner with regards to on-treatment responses. Those with the IL28B CC genotype (80%) had higher SVRs than those with the CT/TT (56%) genotype (P = 0.010). Multivariate analysis showed that TW8 and TW12 responses were independent predictors of SVR. Serious adverse events occurred in 18.6%: sepsis (2%), decompensation (2.7%) and blood transfusion (14%). Discontinuations occurred in 30.7%, with 18.6% fulfilling stopping rules.

Conclusion: Boceprevir can be used successfully in PR treatment failures with a SVR12 > 80% if they have good on-treatment responses; however, discontinuations occurred in 30% because of virological failure or adverse events.

Keywords: Chronic hepatitis C; Cirrhosis; Lead-in; Null response; Partial response; Rapid virological response; Relapse; Response guided therapy; Treatment failure.

Publication types

  • Multicenter Study

MeSH terms

  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Asia / epidemiology
  • Asian People
  • Australia / epidemiology
  • Biomarkers / blood
  • Chi-Square Distribution
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / ethnology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / ethnology
  • Liver Cirrhosis / virology
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polyethylene Glycols / therapeutic use
  • Proline / adverse effects
  • Proline / analogs & derivatives*
  • Proline / therapeutic use
  • Proportional Hazards Models
  • Prospective Studies
  • RNA, Viral / blood
  • Recombinant Proteins / therapeutic use
  • Recurrence
  • Ribavirin / therapeutic use
  • Time Factors
  • Treatment Failure
  • Viral Load
  • White People

Substances

  • Antiviral Agents
  • Biomarkers
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • 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
  • Proline
  • peginterferon alfa-2b
  • peginterferon alfa-2a