J Clin Virol. 2014 Jan 6. pii: S1386-6532(13)00542-8. doi: 10.1016/j.jcv.2013.12.011. [Epub ahead of print]
BACKGROUND: Telaprevir-based therapy is associated with rapid decline in HCV RNA, enabling the application of early futility rules.
OBJECTIVES: To familiarize physicians with this paradigm, a comprehensive analysis of the most frequent HCV viral load profiles observed during treatment with telaprevir/Peg-IFN/RBV in Phase III trials is provided.
DESIGN: HCV RNA profiles were analyzed from 320 HCV genotype 1 treatment-naïve patients enrolled in the ADVANCE study, and 225 prior Peg-IFN/RBV treatment-experienced patients enrolled in the REALIZE study. Patients received 12 weeks of telaprevir with either 24 or 48 weeks of Peg-IFN alfa-2a/RBV. Patients with missing SVR assessments during follow-up, detectable HCV RNA at end of treatment but who did not have viral breakthrough (vBT), or with early vBT who discontinued telaprevir before time of failure were excluded.
RESULTS: All analyzed patients experienced a rapid decline in HCV RNA (>2.0 log10) by Day 14, irrespective of baseline characteristics and/or prior response to Peg-IFN/RBV (relapse, partial response and null response). Subsequently, HCV RNA continued to decline to undetectable levels in most patients. These patients went on to have one of the following outcomes: sustained virologic response, late vBT (after Week 12, i.e. during the Peg-IFN/RBV phase), or relapse. In the small subset of patients with early vBT or meeting a futility rule before Week 12, HCV RNA usually never became undetectable and/or increased rapidly after reaching the nadir.
CONCLUSIONS: HCV RNA profiles with telaprevir/Peg-IFN/RBV are different from those with Peg-IFN/RBV alone. It is important that clinicians understand these HCV RNA profiles and monitor patient viral load in order to apply futility rules correctly.
Copyright © 2014. Published by Elsevier B.V.
KEYWORDS: HCV RNA, Hepatitis C, Stopping rule, Telaprevir, Viral load
PMID: 24462470 [PubMed - as supplied by publisher]