Boceprevir and telaprevir for chronic genotype 1 hepatitis C virus infection. A systematic review and meta-analysis

Background. Treatment of hepatitis C virus (HCV) infection with newer direct-acting antivirals is unrealistic in some countries because of the lack of availability.Aim. Assess benefits and harms of boceprevir (BOC) and telaprevir (TLV) in treatment of genotype 1 HCV infection, and identifying subgroups with most benefit.Material and methods. Search from 2009-2013 in PubMed, EMBASE, and “gray literature” of published and unpublished randomized trials reporting sustained viral response (SVR) or adverse events (AE) with BOC or TLV + pegylated interferon and ribavirin (PR) in HCV-infected patients; cohorts or case reports for comparison protease inhibitors (PI), evaluation of predictors of SVR, and resistant variants. Cochrane guidelines were applied. Comparisons between PI + PR vs. PR were performed. Main outcomes were expressed as risk-ratios with 95% CIs. Meta-regression and trial sequential analysis were performed.Results. 33 studies (10,525 patients) were analyzed. SVR was higher for PI + PR (RR, 2.05; 95% CI 1.70-2.48). In meta-regression, previously treated patients exhibited greater benefit from PI + PR (RR, 3.47; 95% CI, 2.78-4.33). AE were higher with PI + PR (RR, 1.01; 95% CI, 1-1.03; NNH 77.59), also the discontinuation rate (RR, 1.69; 95% CI, 1.36-2.10, NNH, 18). Predictors of SVR were IL-28 TT, nonblack race, low viral load, age, no cirrhosis, statin use, undetectable viral load at the first anemia episode and at week 2 of treatment, and low IL-6 levels. In conclusion SVR was higher in patients treated with PIs, patients previously exposed to PR showed superior response rates. Specific predictors will determine the best candidates for treatments that will offer real-life therapeutic alternatives.