title: Overall efficacy and safety results of sofosbuvir-based therapies in phase II and III studies.
abstract: The uridine nucleotide analogue sofosbuvir is a selective hepatitis C virus NS5B polymerase inhibitor, active regardless of genotype. We analyzed data on efficacy and safety of sofosbuvir, either in combination with pegylated interferon alfa-2a and ribavirin, or in combination with ribavirin alone as part of an interferon free regimen in more than 1300 patients. Treatment with sofosbuvir for 12 weeks in combination with P/R, in naïve genotype 1 patients was mainly studied in Neutrino. The efficacy of sofosbuvir as part of an all-oral combination including ribavirin alone, was explored in 555 naïve, ineligible and previous treatment failure genotype 2/3 patients. Rates of Sustained Viral Response in genotype 1 and 2 were higher than 85%. For genotype 3 and 4, a European study, Valence, and a US study on patients of Egyptian origin showed that naïve patients are cured at high rates by the all-oral combination given for 24 weeks. The efficacy of sofosbuvir plus P/R for 12 weeks in previous treatment failure genotype 3 has also been demonstrated. Sofosbuvir-based combinations are safe and well tolerated without side effects directly related to the drug. A large body of evidence suggests that sofosbuvir marks a revolution in HCV treatment.
authors.affiliation: Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. Electronic address: a.mangia@tin.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Piazzolla
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects; D000069474:Sofosbuvir; D016896:Treatment Outcome; D014542:Uridine Monophosphate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D014542:Uridine Monophosphate; C100416:peginterferon alfa-2a; D000069474:Sofosbuvir
keywords: DAAs; HCV