Real-world efficacy and safety of glecaprevir/pibrentasvir in Japanese adolescents with chronic hepatitis C: a prospective multicenter study.
Adolescent
Direct-acting antiviral
Glecaprevir
Hepatitis C virus
Pibrentasvir
Journal
Journal of gastroenterology
ISSN: 1435-5922
Titre abrégé: J Gastroenterol
Pays: Japan
ID NLM: 9430794
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
17
10
2022
accepted:
05
02
2023
medline:
30
3
2023
pubmed:
16
2
2023
entrez:
15
2
2023
Statut:
ppublish
Résumé
Part 1 of the DORA study, a 2019 international clinical trial of glecaprevir and pibrentasvir (G/P) treatment in adolescents with chronic hepatitis C virus (HCV) infection, demonstrated high efficacy and safety. However, few reports have considered real-world experience with G/P treatment in adolescents with chronic HCV. The present prospective multicenter study assessed real-world efficacy and safety of G/P treatment in Japanese adolescents with chronic HCV. Subjects between 12 and 17 years old who were treatment-naïve or previously managed with interferon-based regimens were prospectively enrolled and treated with G/P (300 mg/120 mg) once daily for 8 or 12 weeks. The primary efficacy endpoint was sustained virologic response at 12 weeks after treatment completion (SVR12). Adverse effects and laboratory abnormalities were assessed. Twenty-five Japanese patients (15 female) were enrolled from 13 pediatric centers in Japan. Median age was 13 years (range 12-17). Numbers of patients with genotypes 1b, 2a, 2b, and 2b/1b were 6, 12, 6, and 1, respectively. Twenty-two were treatment-naïve, while three had experienced interferon-based treatments. All patients completed G/P treatment (24 for 8 weeks and 1 for 12). Twenty-four achieved SVR12 (96%). Most adverse events were mild. None were serious. G/P significantly decreased serum alanine aminotransferase, γ-glutamyltransferase, and Wisteria floribunda agglutinin-positive Mac-2-binding protein concentrations. No negative effects on growth or maturation were apparent at 12 weeks. Under real-world conditions, G/P treatment of Japanese adolescents with chronic HCV was highly efficacious and well tolerated.
Sections du résumé
BACKGROUND
Part 1 of the DORA study, a 2019 international clinical trial of glecaprevir and pibrentasvir (G/P) treatment in adolescents with chronic hepatitis C virus (HCV) infection, demonstrated high efficacy and safety. However, few reports have considered real-world experience with G/P treatment in adolescents with chronic HCV. The present prospective multicenter study assessed real-world efficacy and safety of G/P treatment in Japanese adolescents with chronic HCV.
METHODS
Subjects between 12 and 17 years old who were treatment-naïve or previously managed with interferon-based regimens were prospectively enrolled and treated with G/P (300 mg/120 mg) once daily for 8 or 12 weeks. The primary efficacy endpoint was sustained virologic response at 12 weeks after treatment completion (SVR12). Adverse effects and laboratory abnormalities were assessed.
RESULTS
Twenty-five Japanese patients (15 female) were enrolled from 13 pediatric centers in Japan. Median age was 13 years (range 12-17). Numbers of patients with genotypes 1b, 2a, 2b, and 2b/1b were 6, 12, 6, and 1, respectively. Twenty-two were treatment-naïve, while three had experienced interferon-based treatments. All patients completed G/P treatment (24 for 8 weeks and 1 for 12). Twenty-four achieved SVR12 (96%). Most adverse events were mild. None were serious. G/P significantly decreased serum alanine aminotransferase, γ-glutamyltransferase, and Wisteria floribunda agglutinin-positive Mac-2-binding protein concentrations. No negative effects on growth or maturation were apparent at 12 weeks.
CONCLUSIONS
Under real-world conditions, G/P treatment of Japanese adolescents with chronic HCV was highly efficacious and well tolerated.
Identifiants
pubmed: 36790540
doi: 10.1007/s00535-023-01968-x
pii: 10.1007/s00535-023-01968-x
doi:
Substances chimiques
Antiviral Agents
0
glecaprevir
K6BUU8J72P
glecaprevir and pibrentasvir
0
Interferons
9008-11-1
pibrentasvir
2WU922TK3L
Pyrrolidines
0
Quinoxalines
0
Types de publication
Multicenter Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
405-412Subventions
Organisme : Research Program on Hepatitis from the Japanese Agency for Medical Research and Development, AMED
ID : 22fk0210068h0003
Organisme : Research Program on Hepatitis from the Japanese Agency for Medical Research and Development, AMED
ID : 22fk0210103
Informations de copyright
© 2023. Japanese Society of Gastroenterology.
Références
Polaris Observatory HCV Collaborators. Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study. Lancet Gastroenterol Hepatol. 2022;7:396–415.
doi: 10.1016/S2468-1253(21)00472-6
Schmelzer J, Dugan E, Blach S, et al. Global prevalence of hepatitis C virus in children in 2018: a modelling study. Lancet Gastroenterol Hepatol. 2020;5:374–92.
doi: 10.1016/S2468-1253(19)30385-1
pubmed: 31954439
Tanaka J, Kurisu A, Ohara M, et al. Burden of chronic hepatitis B and C infections in 2015 and future trends in Japan: a simulation study. Lancet Reg Health West Pac. 2022;22:100428.
doi: 10.1016/j.lanwpc.2022.100428
pubmed: 35637862
pmcid: 9142742
Mizuochi T, Takano T, Yanagi T, et al. Epidemiologic features of 348 children with hepatitis C virus infection over a 30-year period: a nationwide survey in Japan. J Gastroenterol. 2018;53:419–26.
doi: 10.1007/s00535-017-1351-0
pubmed: 28567493
Jonas MM, Rhee S, Kelly DA, et al. Pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir in children with chronic HCV: part 2 of the DORA study. Hepatology. 2021;74:19–27.
doi: 10.1002/hep.31841
pubmed: 33811356
Indolfi G, Fischler B, Gonzalez-Peralta RP, et al. Comparison of recommendations for treatment of chronic hepatitis C virus infection in children and adolescents: a position paper of the federation of international societies of pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr. 2020;70:711–7.
doi: 10.1097/MPG.0000000000002710
pubmed: 32205770
Indolfi G, Hierro L, Dezsofi A, et al. Treatment of chronic hepatitis c virus infection in children: a position paper by the hepatology committee of european society of paediatric gastroenterology, hepatology and nutrition. J Pediatr Gastroenterol Nutr. 2018;66:505–15.
doi: 10.1097/MPG.0000000000001872
pubmed: 29287014
Jonas MM, Squires RH, Rhee SM, et al. Pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir in adolescents with chronic hepatitis C virus: part 1 of the DORA study. Hepatology. 2020;71:456–62.
doi: 10.1002/hep.30840
pubmed: 31254392
Lampertico P, Carrión JA, Curry M, et al. Real-world effectiveness and safety of glecaprevir/pibrentasvir for the treatment of patients with chronic HCV infection: a meta-analysis. J Hepatol. 2020;72:1112–21.
doi: 10.1016/j.jhep.2020.01.025
pubmed: 32061651
Hayes CN, Imamura M, Tanaka J, et al. Road to elimination of HCV: clinical challenges in HCV management. Liver Int. 2022;42:1935–44.
doi: 10.1111/liv.15150
pubmed: 34967486
Miura M, Maekawa S, Kadokura M, et al. Analysis of viral amino acids sequences and the IL28B SNP influencing the development of hepatocellular carcinoma in chronic hepatitis C. Hepatol Int. 2012;6:386–96.
doi: 10.1007/s12072-011-9307-6
pubmed: 22020823
Miura M, Maekawa S, Sato M, et al. Deep sequencing analysis of variants resistant to the non-structural 5A inhibitor daclatasvir in patients with genotype 1b hepatitis C virus infection. Hepatol Res. 2014;44:E360–7.
doi: 10.1111/hepr.12316
pubmed: 24612030
Isojima T, Kato N, Ito Y, et al. Growth standard charts for Japanese children with mean and standard deviation (SD) values based on the year 2000 national survey. Clin Pediatr Endocrinol. 2016;25:71–6.
doi: 10.1297/cpe.25.71
pubmed: 27212799
pmcid: 4860518
Balistreri WF, Murray KF, Rosenthal P, et al. The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12–17 years old with hepatitis C virus genotype 1 infection. Hepatology. 2017;66:371–8.
doi: 10.1002/hep.28995
pubmed: 27997679
Schwarz KB, Rosenthal P, Murray KF, et al. Ledipasvir-sofosbuvir for 12 weeks in Children 3 to <6 Years old with chronic hepatitis C. Hepatology. 2020;71:422–30.
doi: 10.1002/hep.30830
pubmed: 31220349
Serranti D, Nebbia G, Cananzi M, et al. Efficacy of sofosbuvir/ledipasvir in adolescents with chronic hepatitis C genotypes 1, 3, and 4: A real-world study. J Pediatr Gastroenterol Nutr. 2021;72:95–100.
doi: 10.1097/MPG.0000000000002900
pubmed: 32810039
Uemura H, Uchida Y, Kouyama JI, et al. NS5A-P32 deletion as a factor involved in virologic failure in patients receiving glecaprevir and pibrentasvir. J Gastroenterol. 2019;54:459–70.
doi: 10.1007/s00535-018-01543-9
pubmed: 30612205
Singh AD, Maitra S, Singh N, et al. Systematic review with meta-analysis: impact of baseline resistance-associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients. Aliment Pharmacol Ther. 2020;51:490–504.
doi: 10.1111/apt.15633
pubmed: 31943236
Sarrazin C. Treatment failure with DAA therapy: importance of resistance. J Hepatol. 2021;74:1472–82.
doi: 10.1016/j.jhep.2021.03.004
pubmed: 33716089
Izumi N, Takehara T, Chayama K, et al. Sofosbuvir-velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals. Hepatol Int. 2018;12:356–67.
doi: 10.1007/s12072-018-9878-6
pubmed: 30030720
Sezaki H, Suzuki F, Hosaka T, et al. Initial- and re-treatment effectiveness of glecaprevir and pibrentasvir for Japanese patients with chronic hepatitis C virus-genotype 1/2/3 infections. J Gastroenterol. 2019;54:916–27.
doi: 10.1007/s00535-019-01575-9
pubmed: 30903385
Tacke F, Klinker H, Boeker KHW, et al. Elevated liver enzymes predict morbidity and mortality despite antiviral cure in patients with chronic hepatitis C: data from the german hepatitis C-registry. Hepatol Commun. 2022. https://doi.org/10.1002/hep4.2015 .
doi: 10.1002/hep4.2015
pubmed: 35666055
pmcid: 9426389
Singh S, Facciorusso A, Loomba R, et al. Magnitude and kinetics of decrease in liver stiffness after antiviral therapy in patients with chronic hepatitis C: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2018;16:27-38.e4.
doi: 10.1016/j.cgh.2017.04.038
pubmed: 28479504
Ura K, Furusyo N, Ogawa E, et al. Serum WFA(+) -M2BP is a non-invasive liver fibrosis marker that can predict the efficacy of direct-acting anti-viral-based triple therapy for chronic hepatitis C. Aliment Pharmacol Ther. 2016;43:114–24.
doi: 10.1111/apt.13431
pubmed: 26503582
Tajiri H, Suzuki M, Bessho K, et al. The role of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in the assessment of fibrosis in children with chronic hepatitis C. Sci Rep. 2022;12:11205.
doi: 10.1038/s41598-022-14553-8
pubmed: 35778417
pmcid: 9249794
Jonas MM, Balistreri W, Gonzalez-Peralta RP, et al. Pegylated interferon for chronic hepatitis C in children affects growth and body composition: results from the pediatric study of hepatitis C (PEDS-C) trial. Hepatology. 2012;56:523–31.
doi: 10.1002/hep.25690
pubmed: 22383118