final program.qxd - Parallels Plesk Panel

the consensus interferon dose (25,26). A recent randomized open-label pilot study
demonstrated that daily consensus interferon plus ribavirin in non responders patients to
interferon and ribavirin had an early virological response rate of 82% and a sustained
virological response rate of 22% (27). In this study, induction dosing resulted in a greater
first phase HCV-RNA decay that, however, did not translate to better sustained virological
response rate , presumably due to more dose modification. The combination of high-dose
interferon alfacon-1 (15 µg/day for 12 weeks then 15µg three times weekly for 36 weeks)
and ribavirin (800/1000 mg/day) in pegylated interferon combination therapy
non-responders was associated with a 43% end of treatment virological response and a
37% SVR(28). In another pilot study, the combination of high-dose interferon alfacon-1
(15 µg/day) and interferon gamma-1b (50µg three times per week) in a similar
non-responding group led to a virological response at the end of treatment in 44% of
patients (48% in genotype 1 patients)(23).
Exploratory triple combination therapy studies using mycophenolate mofetil (an
immunosuppressant which acts by potent inhibition of inosine monophosphate de
hydrogenase and is commonly used in the transplantation setting) have failed to
demonstrate any significant increase in the SVR rate compared with standard therapy
among previous non-responders or relapsers (16,29)
b) Longer treatment durations and higher doses
Other strategies currently under investigation to improve upon the current SVR rates seen
in retreatment include the use of a higher dose of pegylated interferon and/or ribavirin, and
extension of the treatment duration to beyond the 48-week maximum currently
recommended.
The efficacy of high induction doses of peginterferon alfa-2a (40KD) has recently been
evaluated in a randomised, phase II study involving 72 patients with HCV genotype 1
infection who had failed to respond to previous conventional interferon plus ribavirin (10).
In this trial, high induction doses of peginterferon alfa-2a (40KD) (360 or 270 µg/week for
the first 12 weeks, followed by standard dose for 36 weeks) plus ribavirin produced an
EVR in 46 and 35% of patients, respectively, compared with only 21% in patients who
received standard-dose peginterferon alfa-2a (40KD) plus ribavirin. At week 72, respective
SVR rates were 38% and 30% vs 18%. Data from the TARGET trial, which assessed a
high dose of peginterferon alfa-2b (12KD) (3.0 g/kg/week) plus ribavirin for 48 weeks,
compared with a standard dose of 1.5 g/kg/week plus ribavirin, in HCV genotype 1
non-responders or relapsers (to conventional interferon mono- or combination therapy)
demonstrated that administration of high-dose peginterferon alfa-2b (12KD) led to a
sustained virological response rate of 25% in previous relapsers and 14% in previous non
responders. The SVR rate was also different according to previous regimen : 25% of SVR
rate in patients treated with conventional combination therapy and 15% in patients treated
with pegylated combination therapy. Finally, outcomes from a randomised pilot study
indicate that higher doses of peginterferon alfa-2b (12KD) administered on a twice-weekly
basis may improve SVR rates in difficult-to-treat patients, when compared with a standard
weekly dosing regimen. The differences, however, were not statistically significant in
non-responder patients(30).
To our knowledge, there is a lack of published data on the potential benefits of extending
the duration of treatment for previous non-responders, although this is currently under
investigation (31). However, evidence from the treatment-naive population has indicated
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