Boceprevir triple therapy of chronic HCV genotype 1 (G1) infection in previously untreated patients: Efficacy, predictability of virologic response and safety in German real-life

Background: Since 2011, triple therapy with the HCV protease inhibitor boceprevir (BOC) is widely used as standard of care for patients (pts) with chronic HCV G1 infection. Here we report the German experience obtained from the NOVUS observational study with respect to efficacy, safety and predictability of virologic outcome in previously untreated pts undergoing BOC triple therapy in real-life.

Methods: From April 2012 until January 2014, 536 pts with G1 infection were recruited in the ongoing NOVUS study by 97 practices and hospitals in Germany. Pts were treated with pegylated interferons (PegIFN) and ribavirin (RBV) together with BOC for 24 to 44 weeks after a 4 weeks lead-in period with PegIFN/RBV. The present interim analysis was restricted to 275 treatment-naïve pts.

Results: Pts distribution was 59% male, 39% aged > 50 years, 37% G1a, 49% G1b, 69% with viral load > 400,000 IU/mL, 5% cirrhotics, 13% under opioid substitution and 4% co-infected with HIV. At treatment week (TW) 8, 72% (173/241) achieved an early virologic response (EVR) which allows shortening of triple therapy to 24 weeks. Until now, SVR was attained by 76% (151/199) in the total population and 87% vs. 46% in pts with/without EVR (p < 0.0001), respectively. Significantly different EVR and SVR rates in various subgroups are summarized in the table. Multivariate stepwise logistic regression analysis identified firstly HCV-RNA ≤400,000 IU/mL (OR = 2.6, P = 0.01), normal GGT levels (OR = 4.0, P < 0.0001) and a HCV-RNA decline > 1log10 at TW4 (OR = 6.9, P < 0.0001) as independent predictors of a high EVR rate and, secondly, normal GGT (OR = 2.9, P = 0.012), age < 50 years (OR = 3.4, P = 0.0009) and HCV-RNA decline > 1log10 at TW4 (OR = 5.6, P = 0.0001) as independent predictors of a high SVR rate. Regarding adverse events, 17% developed thyroid dysfunctions, 4% showed eGFR declines to < 60 mL/min x1.73m2 while 29% and 8% developed moderate (Hb > 8.5 – < 10 g/dL) and severe anemia (Hb< 8.5 g/dL), respectively. Anemia was managed by RBV dose reductions in 64% while 7% received blood transfusions. Only 1 patient was treated with erythropoietin and no pts discontinued triple therapy because of anemia. Regarding achievement of SVR, there were no differences between pts with and without anemia (74% vs. 77%, P = 0.56).

Conclusions: Following treatment of HCV G1 infection with BOC triple therapy in German real-life, 76% of previously untreated pts achieve a SVR. 72% of pts attain an EVR which is associated with a SVR rate of 87%. Normal GGT values at baseline, age < 50 years and a HCV-RNA decline > 1log10 at TW4 are independent predictors of higher EVR and SVR rates.

Corresponding author: Bilzer, Manfred

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