Page 47 - The Flying Publisher Guide to Hepatitis C Treatment

Antiviral therapy in non-responders, relapsers and special populations | 47

dose of PegIFN has no beneficial effect. Multiple logistic
regression analysis indicated that EVR at 12 weeks consistently
predicts SVR in retreated non-responders (Marcellin 2008).

4. Optimizing PegIFN and RBV dosing during retreatment.
When combined with PegIFN, RBV is critical to prevent
relapse after treatment cessation. A small prospective study on
10 patients with HCV genotype 1 infection and high baseline VL
(>800, 000 IU/ml) showed feasibility and high efficacy of
treatment with high RBV doses (Lindhal 2005). RBV was
calculated to achieve a steady-state concentration above 15
µmol/ml. Prophylactic and as-needed administration of
erythropoietin and blood transfusions were required in a single
patient. SVR was achieved in 9 of 10 patients without major
treatment regimen violation. RBV dosing at 13-15 mg/kg appears
to be the best balance between optimized efficacy and
intolerable hemolytic anemia that develops at high doses. SVR is
significantly diminished when RBV dose is below 11 mg/kg.
Therefore, maximizing RBV dosing, particularly in overweight
patients, has the potential to improve SVR during the second
course of therapy. In a retrospective analysis of a large database
of patients treated with PegIFN/RBV, it has been demonstrated
that RBV dose reduction led to a stepwise decrease in SVR. The
cumulative dose of RBV below 60% is associated with an evident
decline in SVR (Reddy 2007). Thus, not only maximizing RBV
dosing, but also maintaining a cumulative RBV dose higher
than 80% of the overall dose, with or without erythropoietin,
improves SVR in previous non-responders and relapsers.
Other trials (Fried 2006) demonstrated improved SVR in patients
with body weight above 85 kg treated with higher dose of
PegIFN/RBV. Patients treated with PegIFN alfa-2a, 270 µg/week
and RBV 1600 mg/day, showed an SVR of 48% versus 28% in
those treated with standard dosing regimen (relapse rates 19%
vs. 40%). However, higher dose regimen was associated with an
increased rate of hematological AEs.