Pegasys + Ribavirin: 24 vs 48 weeks; 800 vs 1000/1200 ribavirin (EASL), April 18-21, 2002

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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

I arrived in Madrid at 9:30am this morning on an all-night flight

that

left

NYC at 8:30pm the night before. I’ve never been in Madrid before

and

it

appears to be a very nice and clean city. I had to rush over to the

convention center after checking into my hotel in order to catch the

opening

session at this conference.

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 <2 million copies/ml vs high viral load of

>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.

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