Telaprevir versus boceprevir in chronic hepatitis C: a meta-analysis of data from phase II and III trials.
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.
Massachusetts College of Pharmacy & Health Sciences, Worcester, MA 01608, USA. mugdha.sitole@mcphs.edu
Mugdha
M
Sitole
Matthew
M
Silva
Linda
L
Spooner
Morgan K
MK
Comee
Michael
M
Malloy
D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use
D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; 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