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A Dose‐Ranging Study of Pegylated Interferon Alfa‐2b and Ribavirin in Chronic Hepatitis C
Author(s) -
Glue Paul,
RouzierPanis Regine,
Raffanel Claude,
Sabo Ron,
Gupta Samir K.,
Salfi Margaret,
Jacobs Shiela,
Clement Robert P.
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.16661
Subject(s) - ribavirin , medicine , pegylated interferon , gastroenterology , pharmacokinetics , hepatitis c virus , hepatitis c , pharmacology , adverse effect , peg ratio , immunology , virus , finance , economics
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 μg/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. (Hepatology 2000;32:647‐653.)