7%) either withdrew from the study at week 12 or
were nonresponders, and treatment was stopped as defined in the protocol buy R428 (Fig. 1). Patient demographics were generally similar across the treatment groups (Table 1). A baseline viral load >800,000 IU/mL was more common in slow responders than patients with cEVR. In total, eight patients in group A and 17 patients in group B failed to complete the study (Fig. 1). All eight patients in group A discontinued treatment between weeks 24 and 48. Of the 17 slow responders in group B who failed to complete treatment, 11 discontinued treatment between weeks 24 and 48, and six discontinued treatment between weeks 49 and 72. Reasons for discontinuation in group B were adverse events (n = 6 [4 prior to week 48 and 2 after week 48]), lost to follow-up (n = 1 [prior to week 48]), did not wish to continue (n = 6 [4 prior to week 48 and 2 after week 48]), noncompliance (n = 2 [1 prior to week 48 and 1 after week 48]), and other reasons (n = 2 [1 prior to week 48 and 1 after week 48]). In total, 721 of 1,427 (50.5%) patients who received treatment per protocol attained an SVR. Among
patients with cEVR, 27.5% had undetectable HCV RNA at week 4 of treatment (rapid virologic response), and 71.4% had undetectable HCV RNA at week 8. In the intent-to-treat analysis, SVR rates were similar in groups A and B (43% versus 48%; P = 0.6445) and higher in group C (80%; P < 0.0001 versus group A) (Fig. 2). End-of-treatment response was 83%, 70%, http://www.selleckchem.com/products/SP600125.html and 89% in groups A, Flavopiridol (Alvocidib) B, and C, respectively. Relapse rates were 47% for group A and 33% for group B; however, the difference was not statistically
significant (P = 0.1699). Relapse rates were significantly lower for group C compared with group A (10% versus 47%; P < 0.0001). Among adherent patients (those who received ≥80% of the planned dose of each drug for ≥80% of the assigned treatment duration), SVR rates were 44% for group A and 57% for group B (P = 0.20); SVR rates in the per-protocol population were 44% and 49%, respectively (P = 0.63). Similarly, SVR rates in the completers population were 46% and 57% (P = 0.28), and relapse rates were 47.1% and 28.9% in the 48- and 72-week treatment arms, respectively. Slow responders <40 years old were significantly more likely to attain an SVR compared with those >60 years old (odds ratio 3.991; 95% CI 1.043-15.277; P = 0.017). Other variables including weight, treatment arm (group A versus group B), and week 12 HCV RNA levels (<50 versus >5,000 IU/mL or 50-5,000 versus >5,000 IU/mL) did not achieve any statistical significance. There was a trend toward a significant association between week 8 viral load (<2-log versus ≥2-log drop from baseline), 72 weeks of treatment, and SVR among slow responders (odds ratio 2.504; 95% CI 0.948-6.613; P = 0.064). The negative predictive value for a <2-log decline at week 8 was 81% among patients treated for 48 weeks and 62% among those treated for 72 weeks (Fig.