title: Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study.
abstract: Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naive and prior null-responder HCV genotype (GT) 1-infected patients receiving simeprevir+sofosbuvir±ribavirin for 12 or 24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open-label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naive and treatment-experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily+sofosbuvir 400 mg once daily for 12 or 8 weeks. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 weeks versus a composite historical control SVR rate. Enrolled were 310 patients, who were randomized and received treatment (n = 155 in each arm). SVR12 with simeprevir+sofosbuvir for 12 weeks (97% [150/155; 95% confidence interval 94%-100%]) was superior to the historical control (87%). SVR12 with simeprevir+sofosbuvir for 8 weeks (83% [128/155; 95% confidence interval 76-89%]) was not superior to the historical control (83%). The most frequent adverse events were nausea, headache, and fatigue (12-week arm: 15% [23/155], 14% [22/155], and 12% [19/155]; 8-week arm: 9% [14/155], 17% [26/155], and 15% [23/155], respectively). No patients discontinued treatment due to an adverse event. One (1%, 12-week arm) and three (2%, 8-week arm) patients experienced a serious adverse event (all unrelated to study treatment).
  
  
  
  Simeprevir+sofosbuvir for 12 weeks is highly effective in the treatment of HCV GT1-infected patients without cirrhosis, including those with Q80K. (Hepatology 2016;64:370-380).
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis, IN.
authors.forename: Paul
authors.initials: P
authors.lastname: Kwo
authors.affiliation: Atlanta Gastroenterology Associates, Atlanta, GA.
authors.forename: Norman
authors.initials: N
authors.lastname: Gitlin
authors.affiliation: Rutgers University, Robert Wood Johnson Medical School, New Brunswick, NJ.
authors.forename: Ronald
authors.initials: R
authors.lastname: Nahass
authors.affiliation: Hofstra North Shore Long Island Jewish School of Medicine, Manhasset, NY.
authors.forename: David
authors.initials: D
authors.lastname: Bernstein
authors.affiliation: Borland-Groover Clinic, Jacksonville, FL.
authors.forename: Kyle
authors.initials: K
authors.lastname: Etzkorn
authors.affiliation: National Research Institute, Los Angeles, CA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rojter
authors.affiliation: University of Miami Schiff Center for Liver Disease, Miami, FL.
authors.forename: Eugene
authors.initials: E
authors.lastname: Schiff
authors.affiliation: Digestive CARE-South Florida Center of Gastroenterology, Wellington, FL.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Davis
authors.affiliation: Ruane Medical and Liver Health Institute, Los Angeles, CA.
authors.forename: Peter
authors.initials: P
authors.lastname: Ruane
authors.affiliation: GASTRO ONE, Germantown, TN.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Younes
authors.affiliation: Janssen Research and Development LLC, Titusville, NJ.
authors.forename: Ronald
authors.initials: R
authors.lastname: Kalmeijer
authors.affiliation: Janssen Research and Development LLC, Titusville, NJ.
authors.forename: Rekha
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Monika
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Janssen Infectious Diseases BVBA, 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 and Development LLC, Titusville, NJ.
authors.forename: James
authors.initials: J
authors.lastname: Witek
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; 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 / Q000008:administration & dosage*; D000069474:Sofosbuvir / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000069616:Simeprevir; D000069474:Sofosbuvir