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Prediction of Early Virologic Response to Pegasys plus Ribavirin in Patients
with Genotype 1: can 24 hour viral load response predict 72 week outcome
Reported by Jules Levin
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Prediction of Early Virologic Response to Pegasys plus Ribavirin in Patients
with Genotype 1: can 24 hour viral load response predict 72 week outcome
The hypothesis for this study is that the initial virologic response may be
useful to characterize the likely subsequent response to therapy. For
background, Peter Ferenci (Austria) reported that viral decline (of <0.8 log
) 24 hours after a single dose of standard IFN predicts nonresponse to
IFN/RBV combination therapy 100% of the time (Jessner et al, Lancet 2001).
And absence of a virologoic response (of >2 log) after 12 weeks of
Pegasys/RBV (Fried et al, DDW 2001) results 97% of the time in no sustained
response (Ferenci et al, AASLD 2001).
In the Jessner study patients who were treated with IFN 9 or 10 MU dose of
standard interferon and then received IFN/RBV (26 pts IFN/RBV, 21 pts
Pegasys/RBV). The patients who achieved with IFN monotherapy >1.4 log
reduction in viral load in the first 24 hours achieved an SVR (sustained
viral response) 100% of the time with combination Pegasys/RBV; patients with
1.4 to 0.8 log reduction had SVR 33% of the time and patients with <0.8 log
reduction achieved SVR 7.2% of the time.
The goal of the currently reported study at DDW by Peter Ferenci in an oral
presentation was to see if this approach is valid in an ongoing study to see
if using the IFN-sensitivity test can predict the 12-week virologic response
to Pegasys/RBV. In preliminary study the 12 week viral load response has been
shown to have predictive ability for a sustained response (Ferenci, AASLD
2001).
The target number of patients for enrollment in this study is 220. 138 have
been screened, 116 randomized and 65 have been treated for >12 weeks. 8
patients discontinued before week 12. So these reported results are
preliminary as the study has not yet been completed. Patients received 180
mcg Pegasys+ 1000/1200 RBV with amantadine or amantadine placebo.
PRELIMINARY RESULTS
Patients who were HCV-negative at week 12 (n=42) had a 1.17 log decline from
baseline 24 hours after a 9 MU IFN dose. Patients who were HCV-positive at
week 12 had a 0.59 log decline from baseline 24 hrs after a 9 MU IFN dose.
The difference was statistically significant (p=0.00006). There was no
difference in baseline viral load between the group of patients who were HCV
positive or negative.
14/15 patients with >1.4 log decline were viral responders at week 12 while 1
patient was not. 18/25 patients with 0.8-1.39 log decline were responders
while 7 were not. Only 10/28 patients with <0.8 log decline were responders
but this shows that some patients did respond with less than a 0.8 viral load
decline.
After 24 weeks of therapy 10/10 patients who had a decline in viral load 24
hrs after a dose of 9 MU IFN were HCV-negative. 17/19 of patients with
0.8-1.39 log decline were HCV-negative. And 10/17 with <0.8 log decline were
HCV-negative.
The authors concluded that the decline in viral load after one dose of
standard IFN may predict the outcome of Pegasys/RBV therapy. Patients with
less of a response in 24 hrs to a dose of IFN may also be effective. These
findings should be studied further.
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