Eligibility and safety of triple therapy for hepatitis C: lessons learned from the first experience in a real world setting

PLoS One. 2013;8(2):e55285. doi: 10.1371/journal.pone.0055285. Epub 2013 Feb 1.

Abstract

Background: HCV protease inhibitors (PIs) boceprevir and telaprevir in combination with PEG-Interferon alfa and Ribavirin (P/R) is the new standard of care in the treatment of chronic HCV genotype 1 (GT1) infection. However, not every HCV GT1 infected patient is eligible for P/R/PI therapy. Furthermore phase III studies did not necessarily reflect real world as patients with advanced liver disease or comorbidities were underrepresented. The aim of our study was to analyze the eligibility and safety of P/R/PI treatment in a real world setting of a tertiary referral center.

Methods: All consecutive HCV GT1 infected patients who were referred to our hepatitis treatment unit between June and November 2011 were included. Patients were evaluated for P/R/PI according to their individual risk/benefit ratio based on 4 factors: Treatment-associated safety concerns, chance for SVR, treatment urgency and nonmedical patient related reasons. On treatment data were analyzed until week 12.

Results: 208 patients were included (F3/F4 64%, mean platelet count 169/nl, 40% treatment-naïve). Treatment was not initiated in 103 patients most frequently due to safety concerns. 19 patients were treated in phase II/III trials or by local centers and a triple therapy concept was initiated at our unit in 86 patients. Hospitalization was required in 16 patients; one patient died due to a gastrointestinal infection possibly related to treatment. A platelet count of <110/nl was associated with hospitalization as well as treatment failure. Overall, 128 patients were either not eligible for therapy or experienced a treatment failure at week 12.

Conclusions: P/R/PI therapies are complex, time-consuming and sometimes dangerous in a real world setting, especially in patients with advanced liver disease. A careful patient selection plays a crucial role to improve safety of PI based therapies. A significant number of patients are not eligible for P/R/PI, emphasizing the need for alternative therapeutic options.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Eligibility Determination
  • Hepatitis C / drug therapy*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Oligopeptides / therapeutic use*
  • Platelet Count
  • Polyethylene Glycols / therapeutic use*
  • Proline / analogs & derivatives*
  • Proline / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Risk Assessment
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Oligopeptides
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • telaprevir
  • 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-2a

Grants and funding

BM was supported by the Integrated Research and Treatment Center Transplantation (IFB-Tx) funded by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung; BMBF). Publication costs were covered by the DFG (Deutsche Forschungsgemeinschaft)-Project “Open Access Publizieren”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.