G3 patients
with a baseline high viral load (HVL) have lower response rates and higher relapse
rates than G2 patients (Table), but predictors of relapse are not known. The purpose
of this analysis of the WIN-R trial was to determine
the predictors of relapse to PEG-IFN alfa-2b + RBV in patients with HCV G3.
The
WIN-R trial was a multicenter, randomized, open-label, investigator-initiated
trial in 225 US sites that enrolled treatment-naïve HCV patients with compensated
liver disease.
These
patients were randomized to receive PegIntron 1.5?g/kg/wk + fixed dosing (FD;
800mg/d) or weight-based dosing for 24 or 48 wks. HCV RNA was assessed by PCR
at wks 0, 24, 48 and 72. The primary endpoint was SVR (HCV RNA negative at wk
72) in patients >65kg.
Results
G2/3 patients (n=1829) were enrolled and randomized to WBD (24 wks n=317, 48 wks
n=602) or FD (24 wks n=322, 48 weeks n=588).
With WBD and 24 wks of therapy, SVR rates were higher and relapse lower with G2
than G3 patients (SVR: 72% vs 63% and relapse: 5% vs 11%).
Relapse rates were highest among G3 HVL patients treated for 24 weeks (16%).
G3 (vs G2), viral load (high vs low) and duration of treatment (24 vs 48 weeks)
were associated with higher relapse rates in Caucasians.
African Americans (n=47) had a lower relapse rate and no difference between G2
and G3.
Multivariate analyses controlling for the above, race, and steatosis revealed
only G2 vs G3 as a predictor of relapse.
G3 HVL patients had similar relapse rates with WBD/48 wks of therapy than with
FD/24 wks therapy.
According
to the study authors, "Compared with G2 patients, SVR rates are lower and
relapse rates are higher for G3 patients treated with PEG-IFN alfa-2b + RBV."
"When
controlling for viral load, G3 patients do not benefit from longer duration of
therapy or WBD RBV."
"G3
HVL patients appear to benefit from higher RBV dosing but not longer duration
of therapy, mainly through increasing end-of-treatment response not by decreasing
relapse."
SVR, %
Relapse Rate, %
WBD vs FD
WBD vs FD
G2 patients
72 vs 71
4 vs 6
LVL (24/48 wks)
85/86 vs 83/80
6/4 vs 6/11
HVL (24/48 wks)
75/83 vs 79/86
8/0 vs 7/4
G3 patients
63 vs 57
11 vs 12
LVL (24/48 wks)
78/70 vs 64/80
7/16 vs 7/13
HVL (24/48 wks)
79/72 vs 61/68
16/19 vs 17/10
Columbia
Presbyterian Medical Center, New York, NY, USA; Weill Cornell Medical College,
New York, NY, USA; Beth Israel Deaconess Medical Center, New York, NY, USA; Baptist
Medical Center, Kansas City, KS, USA; Kaiser Permanente, Sacramento, CA, USA;
Tulane University Medical School, New Orleans, LA, USA; Northwestern University,
Chicago, IL, USA; Indiana University School of Medicine, Indianapolis, IN, USA;
Austin Gastroenterology, Austin, TX, USA.
11/03/06
Reference R
Brown, I Jacobson, A Nezam, and others. Risk Factors for Relapse in Genotype 3
High Viral Load Patients with Hepatitis C In the WIN-R Trial. 57th AASLD. October
27-31, 2006. Boston, MA. Abstract 1132.
G2/3 patients (n=1829) were enrolled and randomized to WBD (24 wks n=317, 48 wks
n=602) or FD (24 wks n=322, 48 weeks n=588). 
