A randomised trial to compare the pharmacokinetic, pharmacodynamic, and antiviral effects of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C (COMPARE).
OBJECTIVE
To compare the pharmacokinetics, pharmacodynamics, and antiviral activity of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C virus genotype 1.


METHODS
Thirty-six patients were randomised to peginterferon alfa-2b (1.5 microg/kg/week) or peginterferon alfa-2a (180 microg/week) for 4 weeks, then in combination with ribavirin (13 mg/kg/day) for a further 4 weeks. The pharmacokinetic profile of both peginterferons, mRNA expression of a selected group of interferon-induced gene transcripts, and serum HCV-RNA levels were assessed.


RESULTS
Patients receiving peginterferon alfa-2b had significantly greater up-regulation of interferon-alfa response genes compared with those receiving peginterferon alfa-2a. Correspondingly, patients treated with peginterferon alfa-2b also had a significantly greater log10 maximum and log10 time-weighted average decrease in serum HCV-RNA. A greater proportion of peginterferon alfa-2b patients achieved a > or = 2.0 log10 reduction in serum HCV-RNA levels by week 8 (72% vs 44% of peginterferon alfa-2a patients, P = 0.09). There was an approximately 16-fold greater exposure to peginterferon in the serum of patients treated with peginterferon alfa-2a.


CONCLUSIONS
These findings suggest that the biological activity, measured by early interferon-induced gene transcripts and early antiviral responsiveness, may have been greater in patients treated with peginterferon alfa-2b despite their lower exposure to the drug compared with patients treated with peginterferon alfa-2a.
Silva
Marcelo
M
Hospital Universitario Austral, Pilar, Argentina.
Poo
Jorge
J
Wagner
Frank
F
Jackson
Mary
M
Cutler
David
D
Grace
Michael
M
Bordens
Ronald
R
Cullen
Connie
C
Harvey
Joann
J
Laughlin
Mark
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004311:Double-Blind Method; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a