Safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 hepatitis C in subjects aged 65 years or older

Hepatology. 2016 Apr;63(4):1112-9. doi: 10.1002/hep.28425. Epub 2016 Feb 22.

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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / administration & dosage
  • Benzimidazoles / administration & dosage*
  • Clinical Trials, Phase III as Topic
  • Cohort Studies
  • Confidence Intervals
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fluorenes / administration & dosage*
  • Follow-Up Studies
  • Genotype
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Humans
  • Liver Cirrhosis / prevention & control
  • Liver Cirrhosis / virology
  • Male
  • Patient Safety / statistics & numerical data
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Ribavirin / administration & dosage*
  • Risk Assessment
  • Sex Factors
  • Sofosbuvir / administration & dosage*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • ledipasvir
  • Ribavirin
  • Sofosbuvir