Efficacy and Tolerability of Telaprevir for Chronic Hepatitis Virus C Genotype 1 Infection: A Meta-Analysis

<div><h3>Background</h3><p>Chronic hepatitis C virus (HCV) infection is one of the leading causes of hepatic cirrhosis and hepatocellular carcinoma, and HCV genotype 1 is the most prevalent genotype and is resistant to current standard therapy. We performed this meta-analysis to evaluate the efficacy and safety of telaprevir-based therapy for chronic HCV genotype 1 infection.</p> <h3>Methods</h3><p>We included randomized controlled trials with no year or language restriction. All data were analyzed using a random-effects model by Review Manager v5.0. The primary outcome was the proportion of patients achieving sustained virologic response (SVR), and the secondary outcomes were HCV relapse rate, incidence of severe adverse events (SAEs), and discontinuation due to adverse events.</p> <h3>Results</h3><p>The proportion of achieving SVR was significantly higher in the telaprevir group (odds ratio [OR] = 3.40 [1.92, 6.00], <em>P</em><0.0001; <em>I²</em> = 87%) regardless of a patients’ previous treatment status. It was also significantly higher in the 24-week and 48-week treatment groups (OR = 4.52 [2.08, 9.81], <em>P</em><0.001; <em>I²</em> = 85%, and OR = 4.05 [1.56, 10.56], <em>P</em> = 0.004; <em>I²</em> = 92%, respectively), while it was comparable in the 12-week treatment group (OR = 1.32 [0.63, 2.75], <em>P</em> = 0.46; <em>I²</em> = 35%). In addition, the HCV relapse rate was significantly reduced in the telaprevir group (OR = 0.28 [0.16, 0.49], <em>P</em><0.001; <em>I²</em> = 76%). However, the incidence of SAE (OR = 1.56 [1.15, 2.10], <em>P</em> = 0.004; <em>I²</em> = 0%) and study discontinuation due to adverse events (OR = 2.24 [1.43, 3.50], <em>P</em><0.001; <em>I²</em> = 37%) were significantly higher in the telaprevir group.</p> <h3>Conclusion</h3><p>Despite its higher incidence of SAEs and discontinuation due to adverse events, telaprevir-based therapy can increase the proportion of achieving SVR in both previously treated and untreated chronic HCV-1 infected patients.</p> </div

Meta-analysis of telaprevir plus peginterferon and ribavirin therapy on HCV relapse rate according to previous treatment.

<p>The incidence of relapse was significantly reduced in previously untreated (OR = 0.40 [0.16, 1.00], <i>P</i> = 0.05; <i>I²</i> = 78%), treated (OR = 0.18 [0.09, 0.36], <i>P</i><0.001; <i>I²</i> = 71%), and overall population (OR = 0.28 [0.16, 0.49], <i>P</i><0.001; <i>I²</i> = 76%). OR = odds ratio, <i>I²</i> = heterogeneity index. Columns in green represent the mean difference of each study and column size represents the study weight in the analysis. Lanes represent the 95% CI of each study. Diamonds in black represent the overall effect size and diamond width represents the overall 95% CI.</p

Univariate analysis of potential variables influencing the test performance of perforin during AR.

a<p>Three independent data points are required at least to draw an SROC curve.</p><p>Abbreviations: DOR, diagnostic odds ratio; CI, confidence interval; AUC, area under the curve of the SROC curve; PBL, peripheral blood leukocyte; PCR, polymerase chain reaction; RT-PCR, reverse transcription polymerase chain reaction; GAPDH, glyceraldehyde-3-phosphate dehydrogenase.</p

Characteristics of included studies.

<p>T, telaprevir; P, peg-interferon; R, ribavirin; Q8H, every 8 hours.</p

Flow diagram of study identification.

<p>Flow diagram of study identification.</p

Meta-analysis of telaprevir plus peginterferon and ribavirin therapy on SVR according to previous treatment.

<p>The proportion of achieving SVR was significantly higher in the telaprevir group than in the PR group in the previously untreated (OR = 2.25 [1.35, 3.77], <i>P</i> = 0.002; <i>I²</i> = 77%), treated (OR = 6.7 [3.35, 13.41], <i>P</i><0.001; <i>I²</i> = 71%), and overall population (OR = 3.40 [1.92, 6.00], <i>P</i><0.001; I² = 87%). OR = odds ratio, <i>I²</i> = heterogeneity index. Columns in green represent the mean difference of each study and column size represents the study weight in the analysis. Lanes represent the 95% CI of each study. Diamonds in black represent the overall effect size, and diamond width represents the overall 95% CI.</p

Overall DOR and SROC curves for all data sets describing the diagnostic performance of perforin mRNA detection in identifying AR.

<p>(A) Overall DOR. (B) The SROC curves for all data sets. Effect sizes were pooled by random-effects models. The pooled DOR is shown as a solid diamond. Each square in the SROC curve represents one study. Sample size is indicated by the size of the square.</p

Flow chart describing the literature search conducted for this meta-analysis.

<p>Flow chart describing the literature search conducted for this meta-analysis.</p

Sensitivity and specificity of perforin mRNA detection for the diagnosis of AR.

<p>(A) Pooled sensitivity. (B) Pooled specificity. Effect sizes were pooled by random-effects models. The point estimates from each study are shown as solid squares. The pooled estimates are shown as a solid diamond. Error bars represent 95% CIs.</p

Meta-analysis of telaprevir plus peginterferon and ribavirin therapy on SAE incidence.

<p>The incidence of SAE was significantly higher in the telaprevir group than in the PR group (OR = 1.56 [1.15, 2.10], <i>P</i> = 0.004; <i>I²</i> = 0%). OR = odds ratio, <i>I²</i> = heterogeneity index. Columns in green represent the mean difference of each study and column size represents the study weight in the analysis. Lanes represent the 95% CI of each study. Diamonds in black represent the overall effect size and diamond width represents the overall 95% CI.</p