Mericitabine and Either Boceprevir or Telaprevir in Combination with Peginterferon Alfa-2a plus Ribavirin for Patients with Chronic Hepatitis C Genotype 1 Infection and Prior Null Response: The Randomized DYNAMO 1 and DYNAMO 2 StuReport as inadecuate




Mericitabine and Either Boceprevir or Telaprevir in Combination with Peginterferon Alfa-2a plus Ribavirin for Patients with Chronic Hepatitis C Genotype 1 Infection and Prior Null Response: The Randomized DYNAMO 1 and DYNAMO 2 Stu - Download this document for free, or read online. Document in PDF available to download.

Most patients with chronic hepatitis C virus HCV genotype 1 infection who have had a previous null response <2-log10 reduction in HCV RNA by treatment week 12 to peginterferon-ribavirin PegIFN-RBV do not achieve a sustained virological response SVR when re-treated with a first-generation HCV protease inhibitor PI administered in combination with PegIFN-RBV. We studied the incremental benefits associated with adding mericitabine nucleoside analog inhibitor of HCV polymerase to PI plus PegIFN alfa-2a-RBV-based therapy in two double-blind randomized multicenter phase 2 trials with boceprevir in DYNAMO 1, and with telaprevir in DYNAMO 2. The primary endpoint in both trials was SVR, defined as HCV RNA <25 IU-mL 12 weeks after the end of treatment SVR12. Overall, the addition of mericitabine to PI plus PegIFN alfa-2a-RBV therapy resulted in SVR12 rates of 60–70% in DYNAMO 1 and of 71–96% in DYNAMO 2. SVR12 rates were similar in patients infected with HCV genotype 1a and 1b in both trials. The placebo control arms in both studies were stopped because of high rates of virological failure. Numerically lower relapse rates were associated with longer treatment with mericitabine 24 versus 12 weeks, telaprevir-containing regimens, and regimens that included 48 weeks of PegIFN alfa-2a-RBV therapy. No mericitabine resistance mutations were identified in any patient in either trial. The addition of mericitabine did not add to the safety burden associated with either telaprevir or boceprevir-based regimens. These studies demonstrate increased SVR rates and reduced relapse rates in difficult-to-treat patients when a nucleoside polymerase inhibitor with intermediate antiviral potency is added to regimens containing a first-generation PI.Trial Registration: ClinicalTrials.gov NCT01482403 and ClinicalTrials.gov NCT01482390



Author: Heiner Wedemeyer , Xavier Forns, Christophe Hézode, Samuel S. Lee, Astrid Scalori, Athina Voulgari, Sophie Le Pogam, Isabel Náj

Source: http://plos.srce.hr/



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