Low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, viral kinetics and cytokine response.
BACKGROUND
Chronic infection with hepatitis C, genotype 2/3, responds better than other genotypes to peginterferon and ribavirin treatment. We hypothesized that a lower dose of peginterferon would be as effective, but less toxic than standard doses.


OBJECTIVE
To test the hypothesis that a lower dose of peginterferon would be as effective as, but less toxic than, standard doses.


METHODS
A total of 30 patients were treated with low-dose peginterferon alfa-2a (90 microg/week) and 27 patients with standard doses (180 microg/week) for 24 weeks in combination with 800 mg/day of ribavirin. Patients who failed treatment were offered 48 weeks of standard-dose treatment. Viral and serum inducible protein 10 (IP-10) levels were measured and early viral kinetic parameters were calculated.


RESULTS
Sustained virological response was achieved in 68% of the low-dose and 87% of the standard-dose patients (per protocol, P = 0.79 for non-inferiority). Re-treatment was successful in all patients who tolerated full dose and duration. The standard-dose group had greater first-phase declines of viral levels and faster time to negativity. The second-phase slope was not dose-dependent. IP-10 induction was significantly greater with the standard dose. Although fatigue and general feeling during treatment were worse for standard dose, haematological toxicity and depression did not differ between groups.


CONCLUSIONS
A lower dose of peginterferon is associated with some symptomatic benefit, but the response is not equivalent to standard dosing.
Rotman
Y
Y
Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1800, USA. rotmany@mail.nih.gov
Borg
B B
BB
Soza
A
A
Feld
J J
JJ
Modi
A A
AA
Loomba
R
R
Lutchman
G
G
Rivera
E
E
Doo
E
E
Ghany
M G
MG
Heller
T
T
Neumann
A U
AU
Liang
T J
TJ
Hoofnagle
J H
JH
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome
D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a