title: Safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 hepatitis C in subjects aged 65 years or older.
abstract: Elderly subjects have been historically underrepresented in clinical trials involving antiviral hepatitis C therapies. The aim of this analysis was to retrospectively evaluate the safety and efficacy of ledipasvir/sofosbuvir (LDV/SOF) by age groups of <65 years versus ≥65 years among subjects enrolled in phase 3 trials. Four open-label phase 3 clinical trials evaluated the safety and efficacy of LDV/SOF with or without ribavirin (RBV) for the treatment of genotype 1 chronic hepatitis C virus. Sustained virological response at 12 weeks, treatment-emergent adverse events (AEs), and graded laboratory abnormalities were analyzed according to age group. Of the 2293 subjects enrolled in four phase 3 trials, 264 (12%) were ≥65 years of age, of whom 24 were aged ≥75 years. Sustained virological response at 12 weeks was achieved by 97% (1965/2029) of subjects aged <65 years and 98% (258/264) of subjects aged ≥65 years. The most common AEs in both LDV/SOF groups that occurred in ≥10% of subjects were headache and fatigue. The rate of study discontinuation due to AEs was similar in the two age cohorts. The use of RBV in 1042 (45%) subjects increased the number of AEs, treatment-related AEs, and AEs leading to study drug modification/interruption, particularly among elderly subjects.
  
  
  CONCLUSIONS
  LDV/SOF with or without RBV was highly effective for treatment of genotype 1 chronic hepatitis C virusin subjects aged 65 and older. Addition of RBV did not increase sustained virological response at 12 weeks rates but led to higher rates of AEs, especially in elderly subjects.
authors.affiliation: University of California Los Angeles, Los Angeles, CA.
authors.forename: Sammy
authors.initials: S
authors.lastname: Saab
authors.affiliation: University of California Los Angeles, Los Angeles, CA.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Park
authors.affiliation: National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
authors.affiliation: Yamanashi Prefectural Hospital Organization, Yamanashi, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.affiliation: Liver Unit, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Ed
authors.initials: E
authors.lastname: Eggleton
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Knox
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Phil
authors.initials: P
authors.lastname: Pang
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Mani
authors.initials: M
authors.lastname: Subramanian
authors.affiliation: Swedish Medical Center, Seattle, WA.
authors.forename: Kris
authors.initials: K
authors.lastname: Kowdley
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Nezam H
authors.initials: NH
authors.lastname: Afdhal
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage*; D017326:Clinical Trials, Phase III as Topic; D015331:Cohort Studies; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D005500:Follow-Up Studies; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008103:Liver Cirrhosis / Q000517:prevention & control / Q000821:virology; D008297:Male; D061214:Patient Safety / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D018570:Risk Assessment; D012737:Sex Factors; D000069474:Sofosbuvir / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C586541:ledipasvir; D012254:Ribavirin; D000069474:Sofosbuvir