Interferon Responsiveness Does Not Change in Treatment-Experienced Hepatitis C Subjects: Implications for Drug Development and Clinical Decisions

• Published in: Clinical infectious diseases Vol. 55; no. 5; pp. 639 - 644
• Main Authors: Liu, Jiang, Florian, Jeffry, Birnkrant, Debra, Murray, Jeffrey, Jadhav, Pravin R.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2012
• Subjects: Antiviral Agents - therapeutic use; Antiviral drugs; Antivirals; ARTICLES AND COMMENTARIES; Biological and medical sciences; Chronic hepatitis; Comparative analysis; Decision making; Genotypes; Health outcomes; Hepatitis; Hepatitis C; Hepatitis C - blood; Hepatitis C - drug therapy; Hepatitis C - virology; Human viral diseases; Humans; Infections; Infectious diseases; Interferon; Interferon-alpha - therapeutic use; Interferons; Medical sciences; Medical treatment; Odds Ratio; Polyethylene Glycols - therapeutic use; Recombinant Proteins - therapeutic use; Ribavirin - therapeutic use; RNA; RNA, Viral - blood; Transponders; Treatment Outcome; Viral diseases; Viral hepatitis; Viral Load; Infection; Human; Treatment; Viral disease; Cytokine; Digestive diseases; Hepatic disease; Interferon; Viral hepatitis C
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/cis510

Background. The purpose of this research was to compare interferon (IFN) responsiveness in treatment-naive and pegylated interferon α-ribavirin (P/R)—experienced subjects and to understand the implications of comparability in IFN responsiveness across treatment courses on drug development and clinical decision making. Methods. Data from 3750 subjects treated with P/R in 8 trials were reviewed. The change in hepatitis C virus (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-naive 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. Results. In subjects receiving a first course of P/R treatment (treatment-naive subjects), 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 IFN responsiveness in P/R-experienced subjects administered a second course of P/R treatment was similar to the IFN responsiveness in the treatment-naive subjects with corresponding EOS status. Conclusions. We contend that P/R-experienced subjects are represented within treatment-naive subjects. There are 2 important implications of this finding: (1) from a drug development perspective, a successful direct antiviral plus P/R therapy (IFN-based triple therapy) trial in P/R-experienced subjects may serve as supportive evidence in treatment-naive subjects; and (2) from a clinical decision perspective, previous P/R exposure should not alter new treatment decisions involving IFN-based triple therapy, as the IFN responsiveness to a second course of IFN is comparable.