Lindsey M Childs-Kean1, Elizabeth O Hand2. 1. Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Seminole, Florida. Electronic address: Lchilds-kean@cop.ufl.edu. 2. Department of Pharmacotherapy, The University of Texas at Austin College of Pharmacy, The University of Texas Health Science Center at San Antonio Pharmacotherapy Education and Research Center, San Antonio, Texas.
Abstract
PURPOSE: Chronic hepatitis C infection affects a large proportion of the world's population and can lead to significant morbidity and mortality. The standard of care for treatment of hepatitis C infection has been peginterferon and ribavirin, with or without a first-generation protease inhibitor. In late 2013 and early 2014, sofosbuvir and simeprevir obtained regulatory approval, offering the first possibility for all-oral treatment regimens. We provide a review of the clinical efficacy and safety of sofosbuvir- and simeprevir-containing regimens. METHODS: Studies were identified in PubMed using the terms sofosbuvir and simeprevir in combination with hepatitis C. Abstracts of additional studies presented at professional meetings but not yet published were also reviewed. All Phase 3 trials published by August 1, 2014, as well as Phase 2 studies for which there was not a corresponding Phase 3 trial, were included in the review. FINDINGS: Simeprevir was studied with peginterferon and ribavirin in 7 published Phase 3 trials, with overall efficacy rates of 59% to 100%. Sofosbuvir was studied with ribavirin and with or without peginterferon in 6 Phase 3 trials with overall efficacy rates of 50% to 93%. Patient groups with lower response rates tended to have cirrhosis and be older, men, and previous null responders. Simeprevir and sofosbuvir were studied in combination in 1 Phase 2a study with overall efficacy of 92%. Additional studies demonstrated the efficacy and safety of sofosbuvir regimens in patients before and after liver transplantation. Overall, the simeprevir- and sofosbuvir-containing regimens were tolerated better or as well as peginterferon and ribavirin regimens, with fatigue, headache, and nausea the most common adverse events. IMPLICATIONS: Results from numerous Phase 3 clinical trials indicate that sofosbuvir- and simeprevir-containing regimens are highly effective and safe for the treatment of chronic hepatitis C infection. The approval of these 2 agents has led to a complete overhaul of published guidelines, with sofosbuvir- and simeprevir-containing regimens included in preferred regimens.
PURPOSE:Chronic hepatitis C infection affects a large proportion of the world's population and can lead to significant morbidity and mortality. The standard of care for treatment of hepatitis C infection has been peginterferon and ribavirin, with or without a first-generation protease inhibitor. In late 2013 and early 2014, sofosbuvir and simeprevir obtained regulatory approval, offering the first possibility for all-oral treatment regimens. We provide a review of the clinical efficacy and safety of sofosbuvir- and simeprevir-containing regimens. METHODS: Studies were identified in PubMed using the terms sofosbuvir and simeprevir in combination with hepatitis C. Abstracts of additional studies presented at professional meetings but not yet published were also reviewed. All Phase 3 trials published by August 1, 2014, as well as Phase 2 studies for which there was not a corresponding Phase 3 trial, were included in the review. FINDINGS:Simeprevir was studied with peginterferon and ribavirin in 7 published Phase 3 trials, with overall efficacy rates of 59% to 100%. Sofosbuvir was studied with ribavirin and with or without peginterferon in 6 Phase 3 trials with overall efficacy rates of 50% to 93%. Patient groups with lower response rates tended to have cirrhosis and be older, men, and previous null responders. Simeprevir and sofosbuvir were studied in combination in 1 Phase 2a study with overall efficacy of 92%. Additional studies demonstrated the efficacy and safety of sofosbuvir regimens in patients before and after liver transplantation. Overall, the simeprevir- and sofosbuvir-containing regimens were tolerated better or as well as peginterferon and ribavirin regimens, with fatigue, headache, and nausea the most common adverse events. IMPLICATIONS: Results from numerous Phase 3 clinical trials indicate that sofosbuvir- and simeprevir-containing regimens are highly effective and safe for the treatment of chronic hepatitis C infection. The approval of these 2 agents has led to a complete overhaul of published guidelines, with sofosbuvir- and simeprevir-containing regimens included in preferred regimens.