Telaprevir versus boceprevir in chronic hepatitis C: a meta-analysis of data from phase II and III trials.

Abstract

BACKGROUND:

Telaprevir and boceprevir are protease inhibitors now added to therapy for patients with chronic hepatitis C virus (HCV) genotype 1 infection who either are treatment naive or have a history of relapse or recurrence following a previous course of treatment with pegylated interferon + ribavirin (Peg-IFN + RBV). Because these agents are fairly new to the market, providers may have limited experience with them in the management of chronic HCV.

OBJECTIVE:

This meta-analysis compared 24- and 48-week sustained viral responses (SVR) and drug-related adverse events (AEs) between telaprevir and boceprevir triple-therapy regimens in the treatment of chronic HCV infection.

METHODS:

MEDLINE, EMBASE, and Cochrane databases were searched for articles published from January 1995 to October 2012 on randomized controlled trials that reported SVR at ≥24 weeks in patients with HCV receiving triple-therapy regimens that included telaprevir or boceprevir or placebo + pegylated interferon + ribavirin (Peg-IFN + RBV). Pooled odds ratios (ORs) were calculated and used to compare SVR at 24 and 48 weeks. Secondary end points included common drug-related AEs and treatment discontinuations.

RESULTS:

Eight studies were included in this meta-analysis (N = 4144 treatment-naive and treatment-experienced patients). With telaprevir, the ORs (95% CI) for SVR at 24 weeks in treatment-naive and treatment-experienced patients were 3.31 (2.27-4.82; P < 0.0001) and 4.21 (1.83-9.72; P = 0.001), respectively. Telaprevir triple therapy did not result in more drug-related discontinuations but did cause additional rash, pruritis, and anemia. With boceprevir, the ORs (95% CI) were improved in both treatment-naive and treatment experienced patients (3.55 [2.66-4.56; P < 0.0001] and 7.34 [3.92-13.9; P < 0.0001]), but with more treatment-related anemia and dysgeusia.

CONCLUSIONS:

Based on the findings from this meta-analysis, telaprevir or boceprevir combined with Peg-IFN + RBV had favorable short-term data on SVR while resulting in more drug-related AEs. Extended follow-up is required to determine whether these agents offer a reduction in the risk for chronic hepatitis C genotype 1-related mortality and/or hospitalization.

• Authors: Mugdha Sitole, Matthew Silva, Linda Spooner, Morgan K Comee, Michael Malloy
• Journal: Clinical therapeutics (Clin Ther) Vol. 35 Issue 2 Pg. 190-7 (Feb 2013) ISSN: 1879-114X [Electronic] United States
• PMID: 23369368 (Publication Type: Journal Article, Meta-Analysis)
• Copyright: Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Chemical References

• Interferon-alpha
• Oligopeptides
• Protease Inhibitors
• 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

Topics

• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Drug Therapy, Combination
• Hepatitis C, Chronic (drug therapy)
• Humans
• Interferon-alpha (therapeutic use)
• Oligopeptides (administration & dosage, adverse effects, therapeutic use)
• Polyethylene Glycols (therapeutic use)
• Proline (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Protease Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Randomized Controlled Trials as Topic
• Recombinant Proteins (therapeutic use)
• Ribavirin (therapeutic use)