Page 46 - The Flying Publisher Guide to Hepatitis C Treatment

46 | Hepatitis C Treatment

an EVR (56%) during the second course of therapy (Poynard
2008; Poynard 2009).

2. Extended treatment duration for slow virological
responders. Slow virological responders are patients with ≥2
log 10 decline in HCV RNA at treatment week 12, who achieve
undetectable HCV RNA between 12 and 24 weeks of therapy. In
this group, standard 48-week course of therapy has been
associated with a high rate of virological relapse after therapy.
Despite differences in study design (different criteria of
randomization to extended therapy, different doses of RBV),
several randomized controlled trials comparing 72 weeks to 48
weeks of treatment among slow virological responders have
shown consistently that prolonged therapy significantly
improves rates of SVR (44% vs. 28% [Sanchez-Tapias 2006]; 38%
vs. 18% [Pearlman 2007]), largely by decreasing the rate of
relapse (40% vs. 64% [Berg 2006]; 20% vs. 59% [Pearlman 2007]).
However, extending therapy has been associated with a
higher rate of AEs and premature discontinuation beyond 48
weeks of treatment, a finding that temper this approach in many
patients.

3. Increasing PegIFN dose and longer treatment duration.
Trials of intensified regimen with higher fixed-dose of PegIFN
and/or longer treatment duration have demonstrated only
modest increases in SVR in prior non-responders to
PegIFN/RBV. In the REPEAT trial (Jensen 2009) prior non-
responders received PegIFN alfa-2a higher-dose induction
(360µg/week) for 12 weeks, followed by the usual 180µg/week
for a further 60 or 36 weeks (total duration 72 and 48 weeks,
respectively) with RBV 1000-1200 mg/day. The SVR rate was
higher for those treated for 72 weeks; no difference was found
between the induction and non-induction arms. This confirms
that retreatment of non-responders with extended therapy
may improve SVR rates, while induction therapy with higher