AASLD Video Podcast: Concordance of Sustained Virological Response With Sofosbuvir-containing Regimens for HCV
Full text available; Concordance of sustained virological response 4, 12, and 24 weeks post-treatment with sofosbuvir-containing regimens for hepatitis C virus
NEJM Journal Watch
January 23, 2015
SVR12 Is Equivalent to SVR24 in Assessing New HCV Regimens
Atif Zaman, MD, MPH reviewing Yoshida EM et al. Hepatology 2015 Jan.
The two efficacy endpoints were highly concordant in data from phase III trials of sofosbuvir-based regimens.
Eradication of hepatitis C virus (HCV) is typically defined as an undetectable level of HCV RNA 24 weeks after completing treatment (i.e., sustained virologic response at week 24, or SVR24). The FDA recently determined that sustained virologic response at 12 weeks posttreatment (SVR12) is as valid as SVR24 as an efficacy endpoint due to its high rate of concordance with SVR24. However, this concordance has not been extensively studied since the advent of direct-acting antiviral–based regimens.
In a retrospective analysis of data from five phase III trials of sofosbuvir-containing regimens (with and without peginterferon) in 863 patients with HCV infection (genotypes, 1–6), investigators assessed the concordance between SVR at 4 weeks (SVR4) and SVR12, concordance between SVR12 and SVR24, and positive-predictive and negative-predictive values (PPV and NPV).
Rates of SVR4, SVR12, and SVR24 were 92%, 91%, and 91%, respectively, in patients with HCV genotype 1 or 4 through 6; 94%, 92%, and 92% for genotype 2; and 87%, 85%, and 84% for genotype 3. The concordance of SVR4 and SVR12 was 98% (PPV, 98%; NPV, 100%). The concordance of SVR12 and SVR24 was >99% (PPV, >99%; NPV, 100%). Over three fourths (78%) of patients who relapsed post-therapy did so within the first 4 weeks.
COMMENT
This analysis of data from phase III trials of sofosbuvir-based regimens for HCV infection confirms that SVR12 is equivalent to SVR24 as an efficacy endpoint. This is true for direct-acting antiviral regimens that include interferon and for interferon-free regimens. In clinical practice, SVR12 can routinely be used as a marker for treatment success among HCV monoinfected patients with compensated liver disease. Further analysis should be forthcoming regarding special subpopulations such as patients who are coinfected or have decompensated liver disease.
EDITOR DISCLOSURES AT TIME OF PUBLICATION
Disclosures for Atif Zaman, MD, MPH at time of publicationNothing to disclose
CITATION(S):
Yoshida EM et al. Concordance of sustained virological response 4, 12, and 24 weeks post-treatment with sofosbuvir-containing regimens for hepatitis C virus. Hepatology 2015 Jan; 61:41. (http://dx.doi.org/10.1002/hep.27366)
PubMed abstract (Free)
Eradication of hepatitis C virus (HCV) is typically defined as an undetectable level of HCV RNA 24 weeks after completing treatment (i.e., sustained virologic response at week 24, or SVR24). The FDA recently determined that sustained virologic response at 12 weeks posttreatment (SVR12) is as valid as SVR24 as an efficacy endpoint due to its high rate of concordance with SVR24. However, this concordance has not been extensively studied since the advent of direct-acting antiviral–based regimens.
In a retrospective analysis of data from five phase III trials of sofosbuvir-containing regimens (with and without peginterferon) in 863 patients with HCV infection (genotypes, 1–6), investigators assessed the concordance between SVR at 4 weeks (SVR4) and SVR12, concordance between SVR12 and SVR24, and positive-predictive and negative-predictive values (PPV and NPV).
Rates of SVR4, SVR12, and SVR24 were 92%, 91%, and 91%, respectively, in patients with HCV genotype 1 or 4 through 6; 94%, 92%, and 92% for genotype 2; and 87%, 85%, and 84% for genotype 3. The concordance of SVR4 and SVR12 was 98% (PPV, 98%; NPV, 100%). The concordance of SVR12 and SVR24 was >99% (PPV, >99%; NPV, 100%). Over three fourths (78%) of patients who relapsed post-therapy did so within the first 4 weeks.
COMMENT
This analysis of data from phase III trials of sofosbuvir-based regimens for HCV infection confirms that SVR12 is equivalent to SVR24 as an efficacy endpoint. This is true for direct-acting antiviral regimens that include interferon and for interferon-free regimens. In clinical practice, SVR12 can routinely be used as a marker for treatment success among HCV monoinfected patients with compensated liver disease. Further analysis should be forthcoming regarding special subpopulations such as patients who are coinfected or have decompensated liver disease.
EDITOR DISCLOSURES AT TIME OF PUBLICATION
Disclosures for Atif Zaman, MD, MPH at time of publicationNothing to disclose
CITATION(S):
Yoshida EM et al. Concordance of sustained virological response 4, 12, and 24 weeks post-treatment with sofosbuvir-containing regimens for hepatitis C virus. Hepatology 2015 Jan; 61:41. (http://dx.doi.org/10.1002/hep.27366)
PubMed abstract (Free)
Source NEJM Journal Watch
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