title: Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST-2).
abstract: Hepatitis C virus (HCV)-infected patients with cirrhosis are historically a difficult-to-treat population and are at risk of hepatic decompensation. In the phase 2 COSMOS study that evaluated simeprevir (HCV NS3/4A protease inhibitor) + sofosbuvir (HCV nucleotide analogue NS5B polymerase inhibitor) ± ribavirin for 12 or 24 weeks in HCV genotype (GT)1-infected patients, high rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were achieved, including in patients with cirrhosis (METAVIR score F4). This phase 3, open-label, single-arm study (OPTIMIST-2 [NCT02114151]) evaluated the efficacy and safety of 12 weeks of simeprevir + sofosbuvir in HCV GT1-infected treatment-naive or treatment-experienced patients with cirrhosis. Patients (aged 18-70 years) with chronic HCV GT1 infection and documented presence of cirrhosis received oral simeprevir 150 mg once daily + sofosbuvir 400 mg once daily for 12 weeks. The primary efficacy endpoint of the study was the proportion of patients achieving SVR12 versus a composite historical control (SVR12 rate of 70%). Safety and patient-reported outcomes were assessed. Overall, 103 patients received treatment. SVR12 with simeprevir + sofosbuvir (83%, 95% confidence interval 76%-91%) met the primary objective of superiority versus the historical control (70%). SVR12 rates for treatment-naive and treatment-experienced patients were 88% (44/50) and 79% (42/53), respectively. Adverse events occurred in 72 (70%) patients, with most (64%) being grade 1 or 2. Serious adverse events (none considered related to study treatment) occurred in five (5%) patients, and three (3%) patients discontinued all study treatment due to adverse events. Patient-reported outcomes improved from baseline to follow-up week 12.
  
  
  
  Simeprevir + sofosbuvir for 12 weeks achieved superiority in SVR12 rates versus the historical control in treatment-naive and treatment-experienced HCV GT1-infected patients with cirrhosis and was generally safe and well tolerated. (Hepatology 2016;64:360-369).
authors.affiliation: Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX.
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.affiliation: The Gastroenterology Group of South Jersey, Vineland, NJ.
authors.forename: Gary
authors.initials: G
authors.lastname: Matusow
authors.affiliation: Orlando Immunology Center, Orlando, FL.
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.affiliation: University of British Columbia, Vancouver, BC, Canada.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Yoshida
authors.affiliation: Private practice, Bakersfield, CA.
authors.forename: Franco
authors.initials: F
authors.lastname: Felizarta
authors.affiliation: Texas Clinical Research Institute, Arlington, TX.
authors.forename: Reem
authors.initials: R
authors.lastname: Ghalib
authors.affiliation: University Hepatitis Center at Pointe West Infectious Diseases, Bradenton, FL.
authors.forename: Eliot
authors.initials: E
authors.lastname: Godofsky
authors.affiliation: Quality Medical Research, Nashville, TN.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Herring
authors.affiliation: Digestive Health Specialists, Winston-Salem, NC.
authors.forename: Gary
authors.initials: G
authors.lastname: Poleynard
authors.affiliation: Gastrointestinal Specialists of Georgia, Marietta, GA.
authors.forename: Aasim
authors.initials: A
authors.lastname: Sheikh
authors.affiliation: Concorde Medical Group, New York, NY.
authors.forename: Hillel
authors.initials: H
authors.lastname: Tobias
authors.affiliation: South Denver Gastroenterology, P.C., Denver, CO.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Kugelmas
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ.
authors.forename: Ronald
authors.initials: R
authors.lastname: Kalmeijer
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Monika
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Fevery
authors.affiliation: Janssen Global Services LLC, Titusville, NJ.
authors.forename: Guy
authors.initials: G
authors.lastname: De La Rosa
authors.affiliation: Janssen Global Services LLC, High Wycombe, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Scott
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ.
authors.forename: Rekha
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ.
authors.forename: James
authors.initials: J
authors.lastname: Witek
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069616:Simeprevir / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000069616:Simeprevir; D000069474:Sofosbuvir