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Abstract Details
Safety and tolerability of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic hcv genotype 1 infection: Analysis of phase 3 ION trials
Alqahtani SA1, Afdhal N2, Zeuzem S3, Gordon S4, Mangia A5, Kwo P6, Fried M7, Yang JC8, Ding X8, Pang PS8, McHutchison JG8, Pound D9, Reddy KR10, Marcellin P11, Kowdley KV12, Sulkowski M1. Hepatology. 2015 May 11. doi: 10.1002/hep.27890. [Epub ahead of print]
Author information
1Johns Hopkins Hospital, Baltimore, MD.
2Beth Israel Deaconess Medical Center, Boston, MA.
3Johann Wolfgang Goethe University, Frankfurt, Germany.
4Henry Ford Health System, Detroit, MI.
5Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
6Indiana University School of Medicine, Indianapolis, IN.
7University of North Carolina Health Care, Chapel Hill, NC.
8Gilead Sciences, Inc., Foster City, CA.
9Indianapolis Gastroenterology Research Foundation, Indianapolis, IN.
10Hospital of the University of Pennsylvania, Philadelphia, PA.
11Centre Hospitalier Universitaire Beaujon, Clichy-sous-Bois, France.
12Swedish Medical Center, Seattle, WA.
Abstract
In phase 3 studies, treatment with the once-daily fixed-dose combination tablet of ledipasvir/sofosbuvir with and without ribavirin resulted in high rates of sustained virologic response in patients chronically infected with genotype 1 hepatitis C virus (HCV), including those with compensated cirrhosis. We conducted an analysis of data from these trials to compare the safety and tolerability profile of ledipasvir-sofosbuvir with and without ribavirin. We analyzed treatment-emergent adverse events and laboratory abnormalities in patients who were randomized to 8, 12, and 24 weeks of ledipasvir/sofosbuvir with or without ribavirin. In total, data from 1952 patients (of whom 872 received ledipasvir-sofosbuvir with ribavirin and 1080 received ledipasvir-sofosbuvir alone) were analyzed. Overall, 308 patients (16%) were African American, 224 (11%) had compensated cirrhosis, 501 (26%) had a body mass index ≥30 kg/m2 , and 440 (23%) were treatment-experienced. Treatment-related adverse events occurred in 71% and 45% of patients treated with and without ribavirin, respectively, including fatigue, insomnia, irritability and rash/pruritus. Patients receiving ribavirin with ledipasvir/sofosbuvir were more likely to require dose modification, interruptions of treatment due to adverse events, or require the use of concomitant medications than those receiving ledipasvir/sofosbuvir alone. The rates of treatment-related serious adverse events and discontinuations due to adverse events were similarly low (<1%) in both groups. The rate of sustained virologic response in those receiving ribavirin and those not receiving ribavirin was the same (97%).
CONCLUSION:
Ledipasvir-sofosbuvir plus ribavirin was associated with a greater incidence of adverse events, and concomitant medication use than ledipasvir-sofosbuvir alone. The use of ribavirin did not impact the efficacy of ledipasvir/sofosbuvir regimens in the ION phase 3 studies.