A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C

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Hepatology 2000 Sep;32(3):647-53

A dose-ranging study of pegylated interferon alfa-2b

and ribavirin in

chronic hepatitis C.

Glue P, Rouzier-Panis R, Raffanel C, Sabo R, Gupta SK,

Salfi M, s

S,

Clement RP

Schering-Plough Research Institute, Kenilworth, NJ.

The objectives of this study were to assess the

safety,

pharmacokinetics,

and efficacy of pegylated interferon alfa-2b

(PEG-Intron) plus

ribavirin in

patients with chronic hepatitis C. A total of 72

patients (35 men/37

women,

age range 20-68 years) with clinically compensated

chronic hepatitis C

virus

(HCV) were enrolled into this open-label, randomized,

active controlled

study. Patients received either PEG-Intron 0.35, 0.7,

or 1.4 & mgr;g/kg

subcutaneously weekly for 24 weeks alone, or in

combination with

ribavirin

600, 800, or 1,000 to 1,200 mg orally daily. Patients

were evaluated

during

treatment and after a 24-week follow-up period for

safety and efficacy.

Detailed pharmacokinetic assessments were performed at

weeks 1 and 4.

PEG-Intron alone produced expected dose-related

reductions in white

cells,

neutrophils and platelets. Addition of ribavirin

reduced hemoglobin

levels

in a dose-related manner, did not further reduce

PEG-Intron-induced

decreases in neutrophil or white cell count, and

increased platelet

counts.

Neutrophil function tests (C5a and FMLP migration,

killing curves) were

unaltered. Reported adverse events (flu-like symptoms,

asthenia) were

qualitatively similar in all dose groups. Anti-HCV

activity, as

measured by

loss of detectable serum HCV RNA (i.e. <100 copies/mL)

at the end of

treatment (week 24) and after 24 weeks of follow-up

(week 48) showed

dose-response trends for PEG-Intron. At each

PEG-Intron dose level,

anti-HCV

activity was higher in patients coadministered

ribavirin than in

patients

treated with PEG-Intron monotherapy. There was no

evidence of

pharmacokinetic interactions with either drug. We

conclude that the

safety

and tolerability of combined PEG-Intron/ribavirin and

PEG-Intron alone

were

comparable. Combined PEG-Intron/ribavirin showed

dose-related

synergistic

anti-HCV effects, which were numerically superior to

those obtained

with

PEG-Intron monotherapy.

PMID: 10960463, UI: 20417957

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