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 ?mol/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 ?g/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.
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5. Maintenance therapy with low-dose of PegIFN. Nonsustained responders to SoC, with advanced fibrosis or cirrhosis, have a high risk for disease progression and complications. Two large multicentre trials have evaluated the benefits of maintenance therapy with low-dose PegIFN in this group: