Overall, 704 treatment-naive patients who received one or more doses of boceprevir in SPRINT-2 were eligible for the current analysis. SVR was achieved in 475 boceprevir recipients (67%); 9 and 0 of these patients were missing HCV RNA measurements at weeks 8 and 12, respectively. SVR was not achieved in 229 boceprevir recipients (33%); 23 and 34 were missing HCV RNA measurements at weeks 8 and 12, respectively. After stratification in RESPOND-2, 144 partial responders and 259 relapsers were randomized and treated with one or more doses of the study medication. Overall, 316

treatment-experienced patients who received one or more doses of boceprevir in RESPOND-2 were eligible for this analysis; this number included 111 partial responders and 205 relapsers. SVR was achieved in 202 boceprevir recipients (64%); 5 were missing HCV RNA measurements at week 8. SVR was not achieved DMXAA cell line in 114 boceprevir recipients (36%); 11 were missing HCV RNA measurements at week 8. Figure 1 displays scatter plots of HCV RNA levels in 672 and 670 evaluable boceprevir

recipients at weeks 8 and 12, respectively, from SPRINT-2. The recipients were divided into SVR and non-SVR groups. No absolute threshold could be established at week 8 (after 4 weeks of boceprevir) that would have allowed the early discontinuation of failing therapy in patients without the loss of some SVRs (Table 1). All 65 patients with HCV RNA levels ≥100 IU/mL at week 12 failed to achieve SVR; only 3 of these patients (all of whom had week 12 levels <300 IU/mL) reached undetectable levels by the end of find more treatment but subsequently

relapsed. Viral variants first identified after week 12 were found in 36 of the 49 patients (73%) with resistance data who would have stopped therapy at week 12 with the ≥100 IU/mL rule. In 49 of the 79 patients with detectable HCV RNA levels (<100 IU/mL) at week 12, HCV RNA became undetectable between weeks 12 and 24. Ultimately, 21 of these 49 patients achieved SVR. These data indicate that a stopping rule with an HCV RNA cutoff of ≥100 IU/mL at week 12 would have allowed the early discontinuation of failing therapy in 65 of 195 possible failures (sensitivity = 33%) without sacrificing 上海皓元医药股份有限公司 a single SVR among 475 successes (specificity = 100%). A more stringent stopping rule of detectable HCV RNA at week 12 would have sacrificed 21 SVRs. A less stringent stopping rule at week 12 (≥1000 IU/mL) would also have prevented the premature discontinuation of therapy but would have enabled appropriate discontinuation in only 43 patients. Similar results were found with the week 16 stopping rules (Supporting Table 1). In contrast to an absolute HCV RNA threshold level, the degree of the decline from the baseline HCV RNA level was generally a less discriminative predictor of outcomes at most time points. Notably, 24 of 83 patients (29%) with a <0.