Anemia and its management in patients treated with telaprevir twice daily versus every 8 hours in the phase III optimize study.

Background and Aims: OPTIMIZE was a Phase III, randomized, open-label, international, non-inferiority study comparing twice daily (bid) versus every 8 hours (q8h) telaprevir (TVR) combined with peginterferon/ribavirin (PR) in treatment-naive, genotype 1 HCV-infected patients (NCT01241760). We report analyses that describe anemia and its management in this study. Method(s): Anemia was defined as grouped adverse event (AE) terms, including hemoglobin (Hb) <10 g/dL in females and <10.5 g/dL in males. Ribavirin (RBV) dosing, including modifications for anemia, followed local prescribing instructions and was categorized by the amount and timing of dose reduction. Result(s): Anemia was reported in 401/740 (54%) randomized patients, led to TVR discontinuation in <5% and was higher in patients with cirrhosis versus without (65% vs 52%, respectively; p = 0.0165). In a multivariate analysis (N = 731), anemia was associated (p < 0.05) with lower baseline Hb (OR = 1.63), RBV dose (OR = 1.25 per mg/kg), age (OR = 1.67 per decade) and cirrhosis (OR = 1.76), but not with treatment assignment (bid vs q8h), gender, or TVR pharmacokinetics. 340 patients (46%) required interventions for anemia. RBV dose was reduced in 316 (43%; 153/316 [48%] <600 mg/day]), at a median of 9 weeks from TVR initiation and was reduced at similar rates in those with and without cirrhosis (45%) vs 42%, respectively);226/316 (72%) required no additional interventions. 68/740 (9%) required growth factors (ESA);16% with cirrhosis and 8% without (p = 0.0165). 65/740 (9%) required blood transfusion; 14% with cirrhosis and 8% without (p = 0.0551). While SVR12 was lower in patients with cirrhosis versus without (51% vs 77%, respectively; p = 0.0001), the lower SVR12 in cirrhotic patients was not associated with RBV dose reduction but may be explained by other factors such as lower percentages of IL28B CC genotype and RVR in patients with cirrhosis versus without (20% vs 30%; p = 0.0480 and 54% vs 71%; p = 0.0009