Optimal dosing frequency of pegylated interferon alfa-2b monotherapy for chronic hepatitis C virus infection.
OBJECTIVE
Pegylated interferon alfa-2b (PEG-IFN-alfa 2b ) has been shown to provide superior efficacy to IFN-alfa 2b in patients with chronic hepatitis C (predominantly genotype 1) infection as measured by viral clearance. This study was conducted to determine the optimal dosing regimen of PEG-IFN-alfa 2b required to obtain a maximum decrease of hepatitis C viral RNA.


METHODS
This was a 24-week, open-label, multicenter, parallel-group, randomized, active-controlled trial in the United Kingdom, France, and Israel. Individuals (n = 61) with chronic hepatitis C infection, genotype 1, received IFN-alfa 2b 3 mIU 3 times weekly for 24 weeks, or PEG-IFN-alfa 2b 1.5 or 3.0 microg/kg/wk, as total weekly full or split doses, for 12 weeks. At week 12, serum RNA titer was measured, and all PEG-IFN-alfa 2b patients continued with 1.5 microg/kg/wk for a further 12 weeks.


RESULTS
Mean serum hepatitis C RNA levels decreased in all groups at weeks 12 and 24. PEG-IFN-alfa 2b 1.5 microg/kg/wk was superior to IFN-alfa 2b in decreasing mean serum hepatitis C RNA ( P < .05 at week 12). The efficacy of split-dose PEG-IFN-alfa 2b 1.5 or 3.0 microg/kg/wk regimens was not significantly different from full-dose PEG-IFN-alfa 2b 1.5 microg/kg/wk. However, there was a significant decrease in neutrophil count in groups receiving PEG-IFN-alfa 2b 3.0 microg/kg/wk or lower, multiple-dose per week regimens.


CONCLUSIONS
PEG-IFN-alfa 2b 1.5 microg/kg once weekly is the optimal dosing frequency for patients with chronic hepatitis C with predominantly genotype 1 infection. More frequent dosing or increasing the dose to 3.0 microg/kg/wk did not result in improved antiviral effects, but did decrease neutrophil counts.
Lurie
Yoav
Y
Tel Aviv Medical Center, Tel Aviv, Israel. danayoavlurie@bezeqint.net
Rouzier-Panis
Regine
R
Webster
George J M
GJ
Dusheiko
Geoffrey M
GM
Laughlin
Mark
M
Jackson
Mary L
ML
Oren
Ran
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005602:France; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D007557:Israel; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012449:Safety; D016896:Treatment Outcome; D006113:United Kingdom; D014774:Virulence / Q000187:drug effects / Q000235:genetics
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b