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Abstract Details
Concordance of Sustained Virologic Response 4, 12, and 24 Weeks Post-Treatment With Sofosbuvir-Containing Regimens for Hepatitis C Virus
Yoshida EM1, Sulkowski MS, Gane EJ, Herring RW Jr, Ratziu V, Ding X, Wang J, Chuang SM, Ma J, McNally J, Stamm LM, Brainard DM, Symonds WT, McHutchison JG, Beavers KL, Jacobson IM, Reddy KR, Lawitz E. Hepatology. 2014 Oct 14. doi: 10.1002/hep.27366. [Epub ahead
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1University of British Columbia, Vancouver, Canada.
Abstract
Historically, clinical trials of regimens to treat chronic infection with the hepatitis C virus (HCV) have used as their primary efficacy endpoint a sustained virologic response (SVR)-defined as HCV RNA levels below a designated threshold of quantification-24 weeks after the end of treatment (SVR24). More recently, regulatory authorities have begun to accept SVR at 12 weeks post-treatment (SVR12) as a valid efficacy endpoint because of its high rate of concordance with SVR24. However, the concordance between SVR12 and SVR24 has not been systematically assessed with new regimens of recently approved direct-acting antiviral agents. The purpose of this study was to assess the concordance between SVR at various post-treatment time points in phase 3 clinical trials of sofosbuvir-containing regimens. We conducted a retrospective analysis of 5 trials enrolling 863 patients infected with HCV genotypes 1-6. The concordance between SVR at 4 weeks post-treatment (SVR4) and SVR12, and between SVR12 and SVR24 were determined, as well as positive predictive values (PPV) and negative predictive values (NPV). Overall, 779 of 796 patients (98.0%) with an SVR4 also achieved an SVR12, making the PPV of SVR4 for SVR12 98% and the NPV 100%. Of the 779 patients with an SVR12, 777 (99.7%) also achieved an SVR24, making the PPV of SVR12 for SVR24 >99% and the NPV 100%. Of patients who relapsed post-therapy, 77.6% did so within 4 weeks of completing therapy. Conclusion: Data from phase 3 studies demonstrate that with sofosbuvir-based regimens, with or without interferon, SVR12 and SVR24 correlate closely. Thus SVR12 can be used effectively to determine "cure" rates in trials and in clinical practice.