Utility
of Virological Response at Weeks 4 and 12 in the Prediction of SVR in Genotype
2/3 Patients: ACCELERATE Trial Results
ACCELERATE
is a prospective, randomized trial of 1469 genotype
2 or 3 chronic hepatitis C patients which showed that, overall, 24 weeks of
treatment with pegylated
interferon alfa-2a (Pegasys) plus ribavirin is superior to 16 weeks. These
results confirm the current recommended duration of treatment.
Using
data form this study, investigators determined on-treatment predictability of
response at week 4 and week 12, and assessed the clinical utility of rapid and
early response in the management of genotype 2 and 3 patients.
In
the ACCELERATE trial, treatment-naive genotype 2/3 patients received Pegasys 180
mcg/wk plus ribavirin 800 mg/day for 16 or 24 weeks. The ability of rapid
virological response (RVR) at week 4 (undetectable HCV RNA < 50IU/mL) and
early virological response (EVR) at week 12 (undetectable or unquantifiable HCV
RNA or > 2log drop) to predict sustained virological response (SVR)
(undetectable HCV RNA after 24 weeks post-treatment follow-up) was determined
in the standard population (patients without any major protocol deviations).
Results
24 weeks of Pegasys plus ribavirin was superior to 16 weeks overall, regardless
of genotype or achievement of RVR or EVR.
In the 16 and 24 week arms, respectively:
68% and 65% of patients had a RVR;
99% and 97% achieved EVR
95% and 94% had undetectable HCV RNA at week 12.
Achievement of RVR was a more significant positive predictor of SVR for 24 than
16 weeks (90 vs 82%, P < 0.0007).
In patients without RVR, SVR rates were low, but significantly better with 24
weeks vs 16 weeks.
Although absence of EVR was highly predictive of not achieving SVR (94%), very
few patients did not achieve EVR.
Conclusion
These
results led the study authors to conclude:
"As almost every genotype 2/3 patient treated with [Pegasys] plus ribavirin
had undetectable HCV RNA by week 12, the clinical utility of a 12-week response
was minimal."
"In contrast, a week 4 RVR was important. Genotype 2 and 3 patients with
an RVR had a similarly high chance of achieving SVR with 24 weeks."
"However, genotype 2/3 patients without an RVR had low response rates --
these patients should not be considered 'easy-to-cure' and would likely benefit
from more intensive therapy."
"Detectable vs undetectable HCV RNA at week 4 should be utilized to guide
treatment decisions in genotype 2/3 pts."
VCU
Medical Center, Richmond, VA; St Luke's Center for Liver Disease, Houston, TX;
St Louis University, St Louis, MO; Bach & Godofsky, Bradenton, FL; University
of Florida, Gainsville, FL; Royal Adelaide Hospital, Adelaide, SA, Australia;
Hospital General, Valencia, Spain; Roche, Nutley, NJ; Saarland University Hospital,
Homburg/Saar, Germany.
11/07/06
Reference M
Shiffman, S Pappas, B Bacon, and others. Utility of virological response at weeks
4 and 12 in the prediction of SVR rates in genotype 2/3 patients treated with
peginterferon alfa-2a (40KD) plus ribavirin: findings from ACCELERATE. 57th AASLD.
October 27-31, 2006. Boston, MA. Abstract 340.
24 weeks of Pegasys plus ribavirin was superior to 16 weeks overall, regardless
of genotype or achievement of RVR or EVR. 
