title: Safety and tolerability of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic hepatitis C virus genotype 1 infection: Analysis of phase III ION trials.
abstract: In phase III studies, treatment with the once-daily fixed-dose combination tablet of ledipasvir/sofosbuvir (LDV/SOF) with and without ribavirin (RBV) resulted in high rates of sustained virological response (SVR) in patients chronically infected with genotype 1 hepatitis C virus, including those with compensated cirrhosis. We conducted an analysis of data from these trials to compare the safety and tolerability profile of LDV-SOF with and without RBV. We analyzed treatment-emergent adverse events (AEs) and laboratory abnormalities in patients who were randomized to 8, 12, and 24 weeks of LDV/SOF with or without RBV. In total, data from 1,952 patients (of whom 872 received LDV/SOF with RBV and 1,080 received LDV/SOF alone) were analyzed. Overall, 308 patients (16%) were African American, 224 (11%) had compensated cirrhosis, 501 (26%) had a body mass index ≥30 kg/m(2) , and 440 (23%) were treatment experienced. Treatment-related AEs occurred in 71% and 45% of patients treated with and without RBV, respectively, including fatigue, insomnia, irritability, and rash/pruritus. Patients receiving RBV with LDV/SOF were more likely to require dose modification, interruptions of treatment resulting from AEs, or require the use of concomitant medications than those receiving LDV/SOF alone. Rates of treatment-related serious AEs and discontinuations resulting from AEs were similarly low (<1%) in both groups. The rate of SVR in those receiving RBV and those not receiving RBV was the same (97%).
  
  
  CONCLUSIONS
  LDV/SOF plus RBV was associated with a greater incidence of AEs as well as concomitant medication use than LDV/SOF alone. Use of RBV did not impact the efficacy of LDV/SOF regimens in the ION phase III studies.
authors.affiliation: Department of Medicine, Johns Hopkins Hospital, Baltimore, MD.
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Alqahtani
authors.affiliation: Hepatology, Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Nezam
authors.initials: N
authors.lastname: Afdhal
authors.affiliation: Department of Medicine, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Gastroenterology, Henry Ford Health System, Detroit, MI.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
authors.affiliation: Department of Hepatology, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: Gastroenterology-Hepatology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Paul
authors.initials: P
authors.lastname: Kwo
authors.affiliation: Liver Center, University of North Carolina Health Care, Chapel Hill, NC.
authors.forename: Michael
authors.initials: M
authors.lastname: Fried
authors.affiliation: Liver Diseases, Gilead Sciences, Inc, Foster City, CA.
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Liver Diseases, Gilead Sciences, Inc, Foster City, CA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ding
authors.affiliation: Liver Diseases, Gilead Sciences, Inc, Foster City, CA.
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Pang
authors.affiliation: Liver Diseases, Gilead Sciences, Inc, Foster City, CA.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Indianapolis Gastroenterology Research Foundation, Indianapolis, IN.
authors.forename: David
authors.initials: D
authors.lastname: Pound
authors.affiliation: Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.affiliation: Department of Hepatology, Centre Hospitalier Universitaire Beaujon, Clichy-sous-Bois, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, WA.
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.affiliation: Department of Medicine, Johns Hopkins Hospital, Baltimore, MD.
authors.forename: Mark
authors.initials: M
authors.lastname: Sulkowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000627:therapeutic use*; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C000595958:ledipasvir, sofosbuvir drug combination; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir