Source

Division of Pharmacometrics, Office of Clinical Pharmacology, Food and Drug Administration, Silver Spring, MD, USA.

Abstract

BackgroundThe purpose of this research was to compare interferon responsiveness in treatment-naïve and pegylated interferon alfa-ribavirin (P/R) experienced subjects and to understand the implications of comparability in interferon responsiveness across treatment courses on drug development and clinical decision making.MethodsData from 3750 subjects treated with P/R in 8 trials were reviewed. The change in HCV RNA at week 4 in response to P/R was compared according to End of Study (EOS) status (responder, relapser, partial and null responder) for treatment-naïve subjects and the previous P/R response status (known as prior relapsers, prior partial responders, and prior null responders at the baseline) for P/R experienced subjects.ResultsIn subjects receiving a first course of P/R treatment, HCV RNA change after 4 weeks of P/R was correlated with EOS status on a P/R regimen. Importantly, for the first time, we have quantitatively demonstrated that interferon responsiveness in P/R experienced subjects administered a second course of P/R treatment was similar to the interferon responsiveness in the treatment-naïve group with corresponding EOS status.ConclusionsWe contend that P/R-experienced subjects are represented within treatment-naïve subjects. There are two important implications of this finding: (1) from a drug development perspective, a successful direct antiviral plus P/R therapy (interferon-based triple therapy) trial in P/R-experienced subjects may serve as supportive evidence in treatment-naïve subjects (2) from a clinical decision perspective, previous P/R exposure should not alter new treatment decisions involving interferon-based triple therapy as the interferon responsiveness to a second course of interferon is comparable.