Author information
1Janssen Research & Development LLC, Titusville, NJ, USA. Electronic address: gpicchio@its.jnj.com.
2Janssen Infectious Diseases BVBA, Beerse, Belgium.
3Vertex Pharmaceuticals Incorporated, Cambridge, MA, USA.
4Janssen Research & Development LLC, Titusville, NJ, USA.
5Transgene SA, Cambridge, MA, USA.
6Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany.
Abstract
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.