TY - JOUR
T1 - Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11
AU - Murray, Karen F.
AU - Balistreri, William F.
AU - Bansal, Sanjay
AU - Whitworth, Suzanne
AU - Evans, Helen M.
AU - Gonzalez-Peralta, Regino P.
AU - Wen, Jessica
AU - Massetto, Benedetta
AU - Kersey, Kathryn
AU - Shao, Jiang
AU - Garrison, Kimberly L.
AU - Parhy, Bandita
AU - Brainard, Diana M.
AU - Arnon, Ronen
AU - Gillis, Lynette A.
AU - Jonas, Maureen M.
AU - Lin, Chuan Hao
AU - Narkewicz, Michael R.
AU - Schwarz, Kathleen
AU - Rosenthal, Philip
N1 - Funding Information:
Received March 28, 2018; accepted May 29, 2018. R.P. Gonzalez-Peralta’s current address is: Florida Hospital for Children and Florida Hospital Transplant Institute, Orlando, FL. Supported by Gilead Sciences, Inc. © 2018 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.30123
Publisher Copyright:
© 2018 by the American Association for the Study of Liver Diseases.
PY - 2018/12
Y1 - 2018/12
N2 - Currently, there are no interferon-free treatments available for hepatitis C virus (HCV)–infected patients younger than 12 years. We evaluated the safety and effectiveness of the all-oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV-infected children aged 6 to <12 years. In an open-label study, patients aged 6 to <12 years received ledipasvir 45 mg–sofosbuvir 200 mg as two fixed-dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety-two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6-11). Most were perinatally infected (97%) and treatment-naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%-100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration–time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%-200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir–sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.
AB - Currently, there are no interferon-free treatments available for hepatitis C virus (HCV)–infected patients younger than 12 years. We evaluated the safety and effectiveness of the all-oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV-infected children aged 6 to <12 years. In an open-label study, patients aged 6 to <12 years received ledipasvir 45 mg–sofosbuvir 200 mg as two fixed-dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety-two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6-11). Most were perinatally infected (97%) and treatment-naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%-100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration–time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%-200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir–sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.
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U2 - 10.1002/hep.30123
DO - 10.1002/hep.30123
M3 - Article
C2 - 30070726
AN - SCOPUS:85054658137
SN - 0270-9139
VL - 68
SP - 2158
EP - 2166
JO - Hepatology
JF - Hepatology
IS - 6
ER -