Positive and negative prediction of sustained virologic response at weeks 2 and 4 of treatment with albinterferon alfa-2b or peginterferon alfa-2a in treatment-naïve patients with genotype 1, chronic hepatitis C☆
Received 14 November 2008; received in revised form 22 December 2008; accepted 12 January 2009. published online 12 March 2009.
Refers to article:
What offers the best prediction of sustained virologic response during combination therapy with interferon and ribavirin: Viral dynamics, viral levels at certain time points, or a combination of both?
, 17 April 2009
Ola Weiland
Journal of Hepatology
July 2009 (Vol. 51, Issue 1, Pages 4-7) Full Text |
Full-Text PDF (91 KB)
Background/Aims
Albinterferon alfa-2b is a novel, long-acting, fusion polypeptide that is dosed q2wk or q4wk. The predictive value of early virologic response during albinterferon alfa-2b or peginterferon alfa-2a treatment was investigated in interferon-naïve patients with genotype 1, chronic hepatitis C.
Methods
Four hundred and fifty-eight patients were randomized to: albinterferon 900 or 1200μg q2wk, or 1200μg q4wk, or peginterferon 180μg qwk. HCV RNA was measured by real-time PCR. A linear exhaustive search algorithm was used to determine the best SVR prediction algorithm in the per-protocol population (n=368), with inclusion of key ITT analyses to assess impact.
Results
SVR rate: 54–67% (P=NS between arms). Rapid initial virologic response rate at week 2 (RIVR; viral decline >2log10IU/mL) was 32–50% and gave rise to positive predictive value of 88–97% for SVR. No initial virologic response at week 4 (NIVR; viral decline <2log10IU/mL; viral load >5.5log10IU/mL) demonstrated a 100% negative predictive value for SVR. A sequential prediction algorithm based on viral kinetics at weeks 2 and 4 identified four prediction groups that reliably predicted SVR, positively or negatively, in 65–72% of patients.
Conclusions
Improved SVR prediction was obtained by integrating absolute levels and reduction of HCV RNA at treatment week 2 and 4. Patients with RIVR had a high likelihood of achieving SVR.
☆ The authors (except M. Misham) who have taken part in this study have declared a relationship with the manufacturers of the drugs involved. G. Mani Subramanian and E. Pulkstenis are employees of Human Genome Sciences Inc., Rockville, Maryland, USA. J.G. McHutchison has received research grants from HGS, for conduct of this and other clinical trials related to this drug. All funding received from HGS Inc. went towards the cost of the clinical trial. A. Neumann is a consultant for and has received research grants from Human Genome Sciences Inc., Rockville, Maryland, USA. SP, SZ, EMY and YB are all investigators on trails related to this drug. M. Misham has nothing to disclose. ClinicalTrials.gov identifier NCT00115908.
ABSTRACT