1Janssen Research & Development LLC, Titusville, NJ, USA. Electronic address: email@example.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.
Telaprevir-based therapy is associated with rapid decline in HCV RNA, enabling the application of early futility rules.
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.
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.
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.
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.