Introduction: In Australia, and many other countries, the standard treatment for HCV genotype 1 is triple therapy with Pegylated interferon-α-2a/2b, ribavirin (PR) and a first generation direct-acting antiviral (DAA), such as boceprevir (BOC). Uncertainty over the timing of regulatory approval and reimbursement for newer DAAs has led to increasing impetus to treat now to reduce disease progression, especially in advanced liver disease. Current BOC treatment experience data to date is mostly from the northern hemisphere. Thus, we aimed to evaluate the efficacy and safety of BOC based triple therapy in a large Australian cohort reflective of real-world clinical practice.
Methods: A retrospective, observational analysis was conducted in 1026 patients enrolled in an early access program in 65 hepatitis treatment centres. Patients received a PR 4 week lead in followed by either response-guided or fixeddose duration of BOC for 44 weeks according to standard guidelines. Demographic, clinical and virological data were entered into a central database. Cirrhosis was characterised by a composite of radiological imaging, histology (METAVIR 4) and/or transient elastography (median stiffness >12.5 kPa). Virological response (VR) was defined as undetectable HCV RNA using a sensitive quantitative PCR assay.
Results: 407 patients were included in this interim analysis, of whom 308 patients had end of treatment data and 157 had week 12 follow up data. The majority were male (68%) and Caucasian (90%), with mean age of 51 years. Cirrhosis was present in 24% (Child-Pugh A) and 55% had prior PR treatment. HCV genotype 1 distribution was 53% 1a, 16% 1b, 3% 1a/1b, and 28% undifferentiated. IL28B genotype distribution was 20% CC, 35% CT, 7% TT and 38% unknown. Anaemia (Hb <10g/dL) occurred in 42% and Hb reduction >3g/dL in 70%. RBV dose reduction was needed in 33% and blood transfusion in 16%. Infections were rare and there were no deaths. Early treatment discontinuation occurred in 24%, more often due to treatment futility (14%) than adverse events (10%). A sussustained VR at week 12 post-treatment (SVR12) was achieved in 82% (95/115) of non-cirrhotics and 66% (28/42) of cirrhotics. In a multivariate logistic regression analysis, presence of cirrhosis (OR 2.75, p= 0.03, CI 1.1-6.91) and non-IL28B CC (OR 11.73, p= 0.024, CI 1.39-98.69) were associated with failure to achieve SVR12.
Conclusion: In this first multi-centre real-world study of clinical experience with BOC in Australia, treatment of a large well-compensated cohort with BOC demonstrated acceptable efficacy and safety data that were comparable to that in registration studies.