Combination
therapy with pegylated interferon (Pegasys
or PegIntron) plus ribavirin
is standard treatment for chronic hepatitis C. Adequate doses help ensure sustained
response and reduce the chances of HCV
relapse, but both drugs can cause side effects that lead to dose reduction
or treatment discontinuation.
As
background, the authors noted that past studies have shown that reducing doses
of pegylated interferon and/or ribavirin to less than 80% of the original intended
cumulative amount has been associated with a reduction in SVR rates. However,
they said, prior studies did not assess the impact of reducing the dose of pegylated
interferon independent of ribavirin, or differentiate between dose reduction,
treatment interruption, or premature discontinuation of therapy.
The
present study included 936 patients with chronic genotype
1 HCV infection, advanced fibrosis or cirrhosis (Ishak stage 3-6), and prior
non-response to treatment with conventional interferon with or without ribavirin.
Participants were re-treated with 180 mcg/week pegylated interferon alfa-2a (Pegasys)
plus 1000-1200 mg/day ribavirin during the lead-in phase of the HALT-C trial.
Results
•
Reducing the total cumulative dose of pegylated interferon received during the
first 20 weeks of treatment from the full dose (>/= 98%) to </= 60% of the
intended dose:
- reduced week 20 virological response rates from 35% to
12%; - reduced SVR rates from 17% to 5%.
•
Reducing the dose
of ribavirin from the full dose (>/=98%) to </= 60% of the intended dose
did not affect either week 20 virological response or SVR, as long as ribavirin
dosing was not interrupted for more than 7 consecutive days.
•
Premature discontinuation
of ribavirin, even with full-dose pegylated interferon, reduced week 20 virological
response to </= 19% and SVR to </= 4%.
Conclusion
"Reducing
the peginterferon dose during the first 20 weeks of treatment reduced viral clearance
and SVR," the authors concluded. "In contrast, reducing ribavirin did
not affect either [week 20 virological response] or SVR as long as patients remained
on full-dose peginterferon. Discontinuing ribavirin prematurely was associated
with a marked decline in both [week 20 virological response] and SVR.
These
results conflict with those of another
recent study (Reddy et al. 2007), which showed that reducing the cumulative
ribavirin dose to less than 60% of the original intended total dose was associated
with a significantly decreased likelihood of SVR.
02/09/07
References
M
L Shiffman, M G Ghany, T R Morgan, and others. Impact of reducing peginterferon
alfa-2a and ribavirin dose during retreatment in patients with chronic hepatitis
C. Gastroenterology 132(1): 103-112. January 2007.
K
R Reddy, M L Shiffman, T R Morgan, and others. Impact of Ribavirin Dose Reductions
in Hepatitis C Virus Genotype 1 Patients Completing Peginterferon Alfa-2a/Ribavirin
Treatment. Clinical Gastroenterology & Hepatology 5(1): 124-129. January
2007.
