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Pegasys + Ribavirin: 24 vs 48 weeks; 800 vs 1000/1200 ribavirin
37th Annual Meeting of the European Association for the Study of
the Liver (EASL), April 18-21, 2002, Madrid, Spain
Reported by Jules Levin
In this opening oral session Professor Stephanos Hadziyannis
(Dept. of Medicine, Henry Dunany Hospital, Athens, Greece) reported
new information and data from a large study of Pegasys in
combination with ribavirin in HCV monoinfected patients who never
before received interferon or ribavirin.. This study has 4 arms and
compares two dosing schemes of ribavirin (800 mg or 1000/1200 mg
daily) and two treatment dose periods (24 vs 48 weeks). The study
uses the standard dose of Pegasys (180 ug once per week by
subcutaneous injection).Ribavirin are capsules and is dosed either
800 or 1000/1200 mg per day and is dosed twice per day.
A total of 1284 patients were randomized and treated:
Arm A: Pegasys 180 ug once per week + ribavirin 800 mg for 24
weeks
Arm B: Pegasys 180 ug once weekly + ribavirin 1000/1200 mg for 24
weeks
Arm C: Pegasys 180 ug once weekly + ribavirin 800 mg for 48
weeks
Arm D: Pegasys 180 ug once weekly + ribavirin 1000/1200 mg for 48
weeks
There was a 24 week treatment free follow-up period for all
patients after either 24 or weeks study treatment.
Patients were stratified by either genotype 1 or non-genotype 1
and by viral load. Low viral load was less than 2 million copies/ml
vs high viral load of greater than 2 million copies/ml. Patients
were also stratified by geographic region but the author did not
present these results. Patients with wither genotype 1 or non-1
with low viral load were equally distributed among the 4 treatment
arms. Patients with genotype 1 and high viral load were distributed
1:1:4:4 to the 4 arms. So patients with genotype 1 and high viral
load were mostly placed in the 48 week treatment arms because these
patients are the hardest to treat. Treatment duration was blinded
until week 24 and ribavirin dose was blinded throughout the
study.
The primary study goal was to see how many patients achieved
undetectable viral load following either 24 or 48 weeks treatment
and after a 24 week treatment free period (COBAS Amplicor HCV test
v2.0, sensitivity 50 IU/ml). These patient characteristics were
comparable in all 4 study arms: 66% men, 43 years/age, 77 kg. But
the patients in the 48 week treatment arms understandably had
higher viral loads (7.2 million in the 800 mg RBV and 6.1 million
in the 1000/1200 mg RBV) compared to the 24 week groups (5 million
in the 800 mg and 5.5 million in the 1000/1200 RBV group). About
25% had cirrhosis although it was 21% in the 24 week 800 mg arm.
25% is a bit high. 62%-69% had genotype 1 in the 48 week groups vs
42-49% in the 24 week groups.
RESULTS
Sustained Virologic response in Genotype 1
Pegasys + 800 RBV 24 wks (n=101)- 29%
Pegasys + 1000/1200 RBV 24 wks (n=118)- 41%
Pegasys + 800 RBV 48 weeks (n=250)- 40%
Pegasys + RBV 1000/1200 48 wks (n=271)- 51%
Genotype 1 and Low Viral Load
Pegasys + 800 RBV 24 weeks (n=51) - 41%
Pegasys + 1000/1200 RBV 24 weeks (n=71) - 51%
Pegasys + 800 RBV 48 weeks (n=60)- 53%
Pegasys + 1000/1200 RBV 48 weeks (n=85)- 61%
These results find 48 weeks treatment is preferable for genotype 1
and low viral load. The genotype 1/low viral load patients who
received 1000/1200 mg had better results than patients who received
800 mg.
Genotype 1 and High Viral Load (the most prevalent & hardest
group to treat) Pegasys + 800 RBV 24 weeks (n=50)- 16%
Pegasys + 1000/1200 RBV 24 weeks (n=47)- 26%
Pegasys + 800 RBV 48 weeks (n=190)- 35%
Pegasys + 1000/1200 RBV 48 weeks (n=186)- 46%
These data find that genotype 1 and high viral load patients should
be treated for 48 weeks. Patients receiving 1000/1200 RBV did
better than those with 800 mg. This study found that all patients
with genotype 1 whether they had low or high viral load did better
with 48 weeks treatment rather than 24 weeks.
Genotype non-1
Pegasys + 800 RBV 24 weeks (n=106) - 78%
Pegasys + 1000/1200 RBV 24 weeks (n=162)- 78%
Pegasys + 800 RBV 48 weeks (n=111) - 73%
Pegasys + 1000/1200 RBV 48 weeks (n=165) – 77%
Cirrhosis
Patients without cirrhosis had a 65% SVR (n=321) and patients with
cirrhosis had a 50% SVR (treatment was Pegasys + RBV 1000/1200 for
48 weeks).
Rate of Withdrawal From Treatment
3.7% in Pegasys + RBV 800 24 wks
3.5% in Pegasys + RBV 1000/1200 24 weeks
14.2% in the Pegasys + 800 RBV 48 weeks
12.4% in the Pegasys + 1000/1200 RBV 48 weeks
Withdrawal Due To Lab Abnormality
0.9% in Arm A
1.0% in Arm B
1.9% in Arm C
2.7% in Arm D
Ribavirin Discontinuations for Adverse Events/Lab
Abnormalities
7% - Pegasys + 800 RBV 24 weeks
6% - Pegasys + 1000/1200 RBV 24 weeks
18% - Pegasys + 800 RBV 48 weeks
19% - Pegasys + 1000/1200 RBV 48 weeks
Serious Adverse Events
3% (1% treatment-related) in Arm A
7% (3% treatment-related) in Arm B
9% (4% treatment-related) in Arm C
10% (3% treatment-related in arm D
The study authors concluded that using 800 mg of RBV and/or 24
weeks therapy results in reduced efficacy. Lower dose of RBV is
associated with fewer RBV dose modifications, fewer serious adverse
events, and fewer large decreases in hemoglobin.
Submitted by:
Jere Hough * South Florida jlhough@bellsouth.net
Websites: http://pages.prodigy.net/jlhough or
http://home.bellsouth.net/personalpages/pwp-jlhough
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