Concordance of sustained virological response 4, 12, and 24 weeks post‐treatment with sofosbuvir‐containing regimens for hepatitis C virus

Abstract

Historically, clinical trials of regimens to treat chronic infection with hepatitis C virus (HCV) have used, as their primary efficacy endpoint, a sustained virological 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 directacting antiviral agents. The aim of this study was to assess the concordance between SVR at various post-treatment time points in phase III clinical trials of sofosbuvir (SOF)-containing regimens. We conducted a retrospective analysis of five 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 (PPVs) and negative predictive values (NPVs). 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 posttherapy, 77.6% did so within 4 weeks of completing therapy. Conclusion: Data from phase III studies demonstrate that with SOF-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. (HEPATOLOGY 2015;61:41-45)

Liver enzyme normalization predicts success of Hepatitis C oral direct-acting antiviral treatment

“…A key goal of hepatitis C virus (HCV) therapy is to achieve a sustained virologic response (SVR), defined as undetectable serum HCV RNA levels 12 weeks post end of treatment (EOT) [4]. Even with newly approved oral direct-acting antiviral (DAA) regimens replacing interferon (IFN)-based therapy [1,[5][6][7][8], HCV therapy remains lengthy (~12 weeks) and expensive.…”

APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing

“…Recent studies demonstrated that SVR12 (HCV RNA \25 IU/mL 12 weeks after end of treatment) had positive predictive values (PPV) of [98 % for SVR24, regardless of whether therapy was interferon based or DAA interferon free [174,175]. SVR12 is currently widely used as the primary endpoint of clinical trials and regulatory approval for DAA-containing regimens.…”

Pharmacogenomic Testing in the Era of Patient-Tailored HCV Treatment

“…However, with direct-acting agents, that are so much more potent, it has been shown that the viral clearance can be assessed 12 weeks after therapy. Thus, SVR12 is the currently advised standard [14,15]. At the time when interferon (IFN)-α was approved as the first anti-HCV drug in the SVR, it was only achieved in 2-7% of treated patients [16].…”

“…Even though some studies suggested that HCV patients with the IL28B TT genotype had reduced therapeutic efficacy of some DAA regimens, IL28B genotyping did lose importance in the IFN-free era [15,29,92]. Furthermore, in African-American patients infected with HCV GT1a, ribavirin is recommended to be added to ombitasvir plus paritaprevir/ritonavir or dasabuvir treatment regimens to improve cure rates [93].…”