Safety and efficacy of protease inhibitor based combination therapy in a single-center "real-life" cohort of 110 patients with chronic hepatitis C genotype 1 infection

Abstract

Background: The combination of boceprevir or telaprevir with peginterferon-alfa and ribavirin for the treatment of patients infected with HCV genotype 1 has led to significantly increased rates of sustained virological response (SVR) in phase III trials. There is only limited data regarding the safety and efficacy in a "real-life" cohort.

Methods: We analyzed a cohort of 110 unselected HCV patients who started triple therapy from September 2011 to February 2013 by chart review with focus on the individual course of treatment, complications and outcome. We excluded 8 patients from analysis because of HIV-coinfection (N = 6) or status post liver transplant (N = 2). Importantly, 41 patients displayed F3 or F4 fibrosis, 10 patients had a history of treatment with protease/polymerase inhibitors and 15 patients were prior partial- or null-responder.

Results: SVR12 was achieved in 62 of the 102 patients (60.8%). A high rate of serious adverse events (N = 30) was observed in 22 patients including 2 fatalities in cirrhotic diabetes patients. Age >50 years, liver cirrhosis, bilirubin >1.1 mg/dl (P < 0.01, each), platelets <100,000/μl (P = 0.01), ASAT >100 U/l (P = 0.03) and albumin ≤35 g/l (P = 0.04) at baseline were associated with occurence of a SAE.

Conclusions: The frequency of SVR in a "real-life" treatment setting is slightly lower as compared to the results of the phase III trials for telaprevir or boceprevir. Importantly, we observed a high frequency of SAE in triple therapy, especially in patients with liver cirrhosis.

Figure 1

Efficacy of triple therapy. SVR rates for different subgroups are displayed in A and B, a characterization of treatment failures for the total study population [C] and for BOC versus TPR [D] are given, too. Patients who died after discontinuation of therapy (N = 3) and patients who were lost to follow up (N = 8) were not regarded as being at risk for relapse in C and D. [SVR = sustained virological response; BOC = boceprevir; TPR = telaprevir; IL28B = interleukin 28B polymorphism; BT = breakthrough; PI = protease inhibitor].

Figure 2

Individualized courses of treatment in our “real-life” cohort. Patients are grouped according to the respective guidelines [14,15]. Each symbol represents one patient. Patients with partial response or breakthrough under BOC/TPR are not depicted in A and B, patients with partial response or breakthrough at any time are not depicted in C and D. All BOC patients and TPR patients who received a dual lead-in phase prior to BOC/TPR are included in E. [BOC = boceprevir; TPR = telaprevir; PR = pegylated interferon and ribavirin; SVR = sustained virological response; EOT = patient concluded therapy, but is short of 12 weeks after last ribavirin dose].