IntroductionChronic hepatitis C virus (HCV) infection affects 180 million people worldwide [1], and the growing complication of hepatocellular carcinoma has been contributing to increased number of deaths [2]. The sustained virologic response (SVR) for patients with HCV genotype 1 infection was approximately 40% with this previous standard of therapy of pegylated interferon (PEG) and ribavirin (RBV) [3]. In 2011, protease inhibitors, telaprevir and boceprevir, were brought out of phase III clinical trials into the real life setting and have since played a revolutionary role in the treatment for hepatitis C virus genotype 1 infection [4]. Higher SVR rates of 68-79% were achieved in hepatitis C treatment naive patients who received combination therapy of boceprevir or telaprevir along with RBV and PEG during these trials [5,6]. However, the use of these medications as part of triple therapy resulted in increased adverse events and drug-drug interactions. Anemia has emerged as the most significant adverse event associated with both protease inhibitors.Recent phase III trials have shown that triple therapy with telaprevir and boceprevir can cause additional drops in hemoglobin levels when compared to treatment with PEG and RBV alone [5][6][7][8]. The SPRINT-2 trial and RESPOND-2 trial used boceprevir in treatment naïve and treatment experienced HCV patients, respectively, and had a significant anemia event rate of 49% in SPRINT-2 and 43-46% in 7]. The ADVANCE trial and REALIZE trial used telaprevir in treatment naïve and treatment experienced HCV patients respectively, and had a significant anemia event rate of 36% in ADVANCE and 30% in REALIZE [5,8]. The control groups for the boceprevir trials had anemia event rates of 20-29% and the telaprevir trials had anemia event rates of 15-19% [6,7]. During the clinical trials with telaprevir, anemia was treated by dose-reducing RBV, whereas in the boceprevir trials, anemia was treated by RBV dose reduction and the use of epoetin alfa injections (EPO).It is clear that significant anemia was more common in patients treated with protease inhibitors, but this has only been exhibited in the clinical trials. In this study, we investigated the development, natural history, and management of anemia in patients who were treated with telaprevir or boceprevir in the real life setting outside of clinical trials.
AbstractIntroduction: Triple therapy with protease inhibitors, telaprevir and boceprevir, is the new standard of treatment for hepatitis C virus (HCV) genotype 1 infection. In this study, we investigated the natural history of anemia in patients treated with triple therapy compared to those treated with pegylated-interferon and ribavirin (PEG/RBV) in the real-life setting.