Refinement of stopping rules during treatment of hepatitis c-genotype 1 infection with boceprevir combined with peginterferon/ribavirin
Hepatology, 05/31/2012Jacobson IM et al.
Although a stopping rule of detectable HCV–RNA at Week 12 would forfeit some SVR cases, Week–12 HCV–RNA levels ≥100 IU/mL almost universally predicted failure to achieve SVR in both treatment–naïve and treatment–experienced patients. In boceprevir recipients, the combination of stopping rules of HCV–RNA ≥100 IU/mL at Week 12 and detectable at Week 24 maximized early discontinuation of futile therapy while minimizing premature treatment discontinuation.
Exploratory post–hoc analyses using SPRINT–2 (treatment–naïve) and RESPOND–2 (prior treatment–experienced) were undertaken to determine if protocol–specified stopping rules (detectable HCV–RNA at Week 24 for SPRINT–2 and at Week 12 for RESPOND–2) could be refined and harmonized.
In SPRINT–2, a Week–12 rule with a HCV RNA cut–off of ≥100 IU/mL would have discontinued therapy in 65 of 195 failures (sensitivity 33%) without sacrificing a single SVR out of 475 successes (specificity 100%).
Viral variants emerged after Week 12 in 36 (73%) of 49 evaluable patients who would have discontinued at Week 12 using a ≥100 IU/mL rule.
In RESPOND–2, 5 of 6 patients with Week–12 HCV–RNA levels between LLD (9.3 IU/mL) and LLQ (25 IU/mL) who continued therapy despite the protocol–stipulated futility rule achieved SVR; one additional patient with a Week–12 HCV–RNA level of 148 IU/mL also continued therapy, had undetectable HCV–RNA at Week 16, and attained SVR.
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