Impact of reducing peginterferon alfa-2a and ribavirin dose during retreatment in patients with chronic hepatitis C.
OBJECTIVE
Reducing the dose of peginterferon and/or ribavirin to <80% when treating chronic hepatitis C virus has been associated with a reduction in sustained virologic response (SVR). However, prior studies did not assess the impact of reducing the dose of peginterferon independent of ribavirin or differentiate between dose reduction or interrupting or prematurely discontinuing treatment.


METHODS
Nine hundred thirty-six patients with chronic hepatitis C genotype 1, advanced fibrosis, or cirrhosis (Ishak 3-6) and prior nonresponse to standard interferon +/- ribavirin were retreated with peginterferon alfa-2a (180 microg/wk) and ribavirin (1000-1200 mg/day) during the lead-in phase of the HALT-C trial. The percentage of each medication actually taken during treatment was calculated.


RESULTS
Reducing the total cumulative dose of peginterferon received during the first 20 weeks of treatment from full dose (> or =98%) to < or =60% reduced week 20 virologic response (W20 VR) from 35% to 12% and SVR from 17% to 5%. Reducing the dose of ribavirin from full dose (> or =98%) to < or =60% did not affect either W20 VR or SVR as long as ribavirin dosing was not interrupted for more than 7 consecutive days. Prematurely discontinuing ribavirin, even at full-dose peginterferon, reduced W20 VR to < or =19% and SVR to < or =4%.


CONCLUSIONS
Reducing the peginterferon dose during the first 20 weeks of treatment reduced viral clearance and SVR. In contrast, reducing ribavirin did not affect either W20 VR or SVR as long as patients remained on full-dose peginterferon. Discontinuing ribavirin prematurely was associated with a marked decline in both VR and SVR.
Shiffman
Mitchell L
ML
Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA. mshiffma@vcu.edu
Ghany
Marc G
MG
Morgan
Timothy R
TR
Wright
Elizabeth C
EC
Everson
Gregory T
GT
Lindsay
Karen L
KL
Lok
Anna S F
AS
Bonkovsky
Herbert L
HL
Di Bisceglie
Adrian M
AM
Lee
William M
WM
Dienstag
Jules L
JL
Gretch
David R
DR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage*; D001835:Body Weight; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011446:Prospective Studies; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage*; D013997:Time Factors
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a