Response
to PegIntron and Ribavirin in HCV Patients with Body Weight >125 kg: the WIN-R
Trial
The
WIN-R
trial was an American study of >4900 HCV patients that compared PEG-IFN
alfa-2b 1.5ug/kg/wk + fixed dosing (FD; 800 mg/d) or weight-based dosing (WBD;
800-1400 mg/d) of ribavirin (RBV). In this prospective study, researchers determined
that sustained virological response
(SVR) rates were significantly greater with WBD than FD of RBV (results
reported at AASLD 2005).
WBD
patients weighing >105-125 kg received RBV 1400 mg/d and had SVR rates similar
to other WBD patients. The current study evaluated SVR rates among patients weighing
>125 kg, for whom data are limited.
Genotype
1 (G1) patients received 48 wks of therapy, and G2/3 patients were randomized
to 24 or 48 wks of therapy. All patients were monitored for 24 wks post-treatment.
HCV RNA levels were determined by PCR at wks 0, 24, 48 and 72. RBV dose reductions
and discontinuation were required for hemoglobin <10 gm/dl and <8.5 gm/dl.
Results
In total, 42 patients >125 kg were enrolled in the trial (Table); 20 received
FD RBV (800 mg/d) and 22 received WBD RBV (1400 mg/d).
SVR occurred in 45% of patients-33% of G1 and 61% of G2/3 patients, rates nearly
identical to those for the overall study cohort.
SVR rates for the 20 FD RBV patients and the 22 WBD RBV patients were 25% and
64% overall (P=.015); 17% and 50% in G1 (P=.096), and 38% and 50% in G2/3 (P=.078).
Only
2/42 (5%) had nadir Hgb <10 gm/dl and 3/42 (7%) had neutrophils <750/mm3;
for the overall study cohort (n = 4913) these percentages were 16% and 20%.
Dose reductions
of PEG-IFN occurred in 8/42 (19%) patients and 9/42 (21%) had dose reductions
of RBV.
In
conclusion, the authors wrote, "In WIN-R, patients with very high body weight
and BMI had SVR rates similar to those of other study patients, and like the other
patients, WBD RBV conferred superior efficacy to FD RBV in these patients. \"
"The
low rates of nadir hemoglobin and neutropenia and low dose reduction rates probably
reflect lower levels of drug exposure."
"These
results suggest that severe obesity should not preclude consideration of antiviral
therapy for chronic hepatitis C; however, further studies of such patients are
needed."
Mean body weight
132.5 kg (125.4-149.5)
Mean body mass index
41.5 (35.3-55.70)
SVR, %
All patients
n = 42
45 (19/42)
Genotype 1 Genotype 2/3
n = 24 (57%) n = 18 (43%)
33 (8/24) 61 (11/18)
FD RBV (800 mg/d) WBD RBV (1400 mg/d)
n = 20 n = 22
All 25 64 P=.015
G1 17 50 P=.096
G2/3 38 80 P=.078
Weill Medical College
of Cornell University, Center for the Study of Hepatitis C, New York, NY, USA;
Columbia Presbyterian Medical Center, New York , NY, USA; Baptist Medical Center,
Kansas City, MO, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA; Indiana
University School of Medicine, Indianapolis, IN, USA; Atlantic Gastroenterology
Associates, PA, Egg Harbor Township, NJ, USA; Austin Gastroenterology, Austin,
TX, USA; East Bay Liver Clinic, San Francisco, CA, USA; Schering-Plough Research
Institute, Kenilworth, NJ, USA.
This
trial was supported by Schering Plough.
11/03/06
Reference I
M Jacobson, R Brown, B Freilich, and others. Response to Peginterferon Alfa-2b
and Ribavirin for Chronic Hepatitis C in Patients with Body Weight >125 kg:
Results from the WIN-R Trial. 57th AASLD. October 27-31, 2006. Boston, MA. Abstract
369.
In total, 42 patients >125 kg were enrolled in the trial (Table); 20 received
FD RBV (800 mg/d) and 22 received WBD RBV (1400 mg/d). 
This
trial was supported by Schering Plough. 
