In contrast, <2-log and <3-log declines in the HCV RNA levels from baseline to week 8 accurately identified modest numbers of therapeutic failures with only 1 misclassification of a patient eventually achieving SVR, but this strategy would require testing at an additional time point. Figure 2 displays a scatter plot of HCV RNA levels in 300 evaluable boceprevir recipients at week 8 from RESPOND-2. The recipients

were divided into SVR and non-SVR groups. No robust futility rule was evident at week 8 that would have completely prevented missed SVRs (Table 2). However, a week 8 HCV RNA cutoff of ≥1000 IU/mL would have allowed appropriate early discontinuation in 27 patients at the selleck chemicals cost of 1 SVR. Per protocol, 72 patients were to be discontinued for futility because this website of detectable HCV RNA at week 12 (Table 3). In this group, 39 patients

had week 12 levels <100 IU/mL; these patients included 31 with HCV RNA levels between the LLQ (25 IU/mL) and the LLD (9.3 IU/mL). Six of these 31 patients completed the treatment despite the protocol stipulation that such patients discontinue therapy. All six patients had >5.5-log declines from the baseline HCV RNA levels by week 12. Five of the six patients (both patients with a previous partial response and three of the four patients with a previous relapse with P/R) were treated for 48 weeks (including 44 weeks of boceprevir) and achieved SVR; the other patient received 36 weeks of treatment and did not attain SVR. Although detectable HCV RNA levels (<100 IU/mL) at week 12 did not preclude SVR, only one of the eight patients with week 12 levels between 25 and 100 IU/mL continued therapy and achieved HCV RNA undetectability by the end of treatment; this patient relapsed during follow-up. Among the 33 learn more patients with detectable HCV RNA levels (≥100 IU/mL) at week 12, therapy was continued in 1 patient who achieved SVR; the HCV RNA levels in this successfully treated patient were 14,813,507 IU/mL at baseline; detectable (<25 IU/mL) at week 10 (day 71); 103, 125,

and 148 IU/mL in a single specimen (run in triplicate) at week 12 (day 85); and undetectable by week 16 (day 113) and thereafter. Five of the 21 patients (24%) with a <0.5-log decline in the baseline HCV RNA levels at week 4 achieved SVR after the addition of boceprevir. At week 8, a <2-log decline was the only rule with which no SVR was missed, but therapy would have been discontinued in just three patients with this criterion. In all, 195 of the 277 evaluable patients (70%) with a ≥4-log decline at week 12 in their baseline HCV RNA levels achieved SVR; this number includes 6 patients with HCV RNA detectable at week 12 (as described previously). With conventional P/R therapy, generally accepted stopping rules include a <2-log viral load decline at week 12 and/or detectable HCV RNA at week 24.