In this analysis sample, 42% of patients achieved SVR, 23% relapsed, 10% had breakthrough, and 24% were nonresponders. Approximately one-third of the breakthrough and nonresponder patients completed at least 44 weeks of treatment. Of the four trials included in this selleck analysis, epoetin alfa use was only allowed in the Latino study and was received by 10.4% of patients in the Latino group and 18% of patients in the non-Latino Caucasian group.8 The mean ± SD maximum decrease from baseline was 2.5 ± 1.3 × 109/L for neutrophils, 93.6 ± 44.9 × 109/L for platelets, 3.9 ± 1.5 g/dL for hemoglobin, and 6.3% ± 4.7% for weight. The mean maximum decreases in hematologic parameters and weight by virologic response category are shown in Fig. 1. Cirrhosis

was associated with smaller declines in neutrophils and platelets and was therefore included in the final models. The analysis indicated that there was a correlation between virologic response and maximum decreases from baseline in each parameter. Patients with a virologic response (SVR, relapse, and breakthrough) experienced greater declines in neutrophil count, platelet count, hemoglobin level, and weight than nonresponders (P < 0.01 for all parameters except Ku-0059436 supplier for the difference in hemoglobin decline between breakthrough and nonresponders, which was not significant). Among virologic responders, the mean total dose of PEG-IFN alfa-2a was 7,202.8 μg and the mean total dose of ribavirin was 3,803.8 mg/kg.

Among nonresponders, the mean total dose of PEG-IFN alfa-2a was 5,074.3 μg and the mean total dose of ribavirin was 2,474.0 mg/kg. After

adjusting Flavopiridol (Alvocidib) for total PEG-IFN and ribavirin received (Fig. 2A), the differences between virologic responders and nonresponders in neutrophil and platelet count declines remained statistically significant; however, the decreases in hemoglobin level and weight were no longer consistently associated with virologic response. An additional sensitivity analysis that included only a subset of patients who completed at least 44 weeks of therapy (Fig. 2B) showed that after adjusting for drug exposure and taking into consideration duration of therapy, only neutrophil decline was independently associated with virologic response. The mean changes in pharmacodynamic parameters after adjusting for drug exposure from baseline to weeks 4, 12, and 24 for virologic responders and nonresponders are shown in Fig. 3. Following the initiation of combination therapy, rapid decreases in neutrophil count, platelet count, and hemoglobin level were observed, with most of the decline occurring by week 4 for both responders and nonresponders. Significantly greater declines in neutrophil count (P < 0.0001) and platelet count (P < 0.005) were seen at all time points in virologic responders compared with nonresponders. The mean decreases from baseline in hemoglobin level were similar between virologic responders and nonresponders at all time points after adjusting for drug exposure.