The tolerability of sofosbuvir/velpatasvir for 12 weeks in patients treated in the ASTRAL 1, 2 and 3 studies: A pooled safety analysis.
compensated cirrhosis
hepatitis C
safety
sofosbuvir
velpatasvir
Journal
Journal of viral hepatitis
ISSN: 1365-2893
Titre abrégé: J Viral Hepat
Pays: England
ID NLM: 9435672
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
18
01
2023
received:
10
10
2022
accepted:
20
01
2023
medline:
20
4
2023
pubmed:
7
2
2023
entrez:
6
2
2023
Statut:
ppublish
Résumé
To evaluate the safety and tolerability of the fixed-dose, single-tablet regimen sofosbuvir/velpatasvir (SOF/VEL) for the treatment of hepatitis C virus (HCV) infection in three Phase 3 studies in patients with and without compensated cirrhosis. Data from three registrational trials (ASTRAL-1, NCT02201940; ASTRAL-2, NCT02220998; ASTRAL-3, NCT02201953) were pooled by treatment regimen. Researchers assessed treatment-emergent adverse events (TEAEs) and laboratory abnormalities in patients randomized to SOF/VEL or placebo for 12 weeks in ASTRAL-1 and SOF/VEL for 12 weeks in ASTRAL-2 and ASTRAL-3. Overall, 1035 patients were treated with SOF/VEL, and 116 patients received placebo. Rates of any TEAE were generally similar between patients receiving SOF/VEL (79.4%) and those receiving placebo (76.7%). The majority of TEAEs were mild to moderate, with 23 (2.2%) treatment-emergent serious AEs in patients treated with SOF/VEL. Of these treatment-emergent serious AEs, none led to premature study discontinuation, nor were they considered related to treatment. Presence of compensated cirrhosis, greater age and mild renal impairment did not impact incidence or severity of TEAEs with SOF/VEL treatment. The most common TEAEs (incidence ≥10%) were headache, fatigue, nausea and nasopharyngitis in patients receiving SOF/VEL; similar rates were observed in placebo-treated patients. Three deaths (<1%) were reported in patients treated with SOF/VEL, all posttreatment and none assessed as related to study treatment. Similar to that of placebo, SOF/VEL treatment of HCV infection had a safety/tolerability profile that was not affected by baseline factors, such as the presence of compensated cirrhosis, mild renal impairment or advanced age.
Substances chimiques
Sofosbuvir
WJ6CA3ZU8B
velpatasvir
KCU0C7RS7Z
Antiviral Agents
0
Heterocyclic Compounds, 4 or More Rings
0
Banques de données
ClinicalTrials.gov
['NCT02201940', 'NCT02220998', 'NCT02201953']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
448-454Informations de copyright
© 2023 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.
Références
World Health Organization. Hepatitis C. 2021. Accessed November 11, 2021. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c.
World Health Organization. Global health strategy on viral hepatitis, 2016-2021. 2016.
World Health Organization. Guidelines for the Care and Treatment of Persons Diagnosed with Chronic Hepatitis C Virus Infection. 2018. World Health Organization.
Weisberg IS, Jacobson IM. A pangenotypic, single tablet regimen of sofosbuvir/velpatasvir for the treatment of chronic hepatitis C infection. Expert Opin Pharmacother. 2017;18:535-543.
Razavi H, Sanchez Gonzalez Y, Yuen C, Cornberg M. Global timing of hepatitis C virus elimination in high-income countries. Liver Int. 2020;40:522-529.
European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C: final update of the series. J Hepatol. 2020;73:1-49.
Call to action for liver associations to advance progress towards viral hepatits eliminiation: a focus on simplified approaches to HCV testing and cure. 2019. Accessed January 26, 2022. https://www.aasld.org/programs-initiatives/viral-hepatitis-elimination-call-action.
Abraham GM, Obley AJ, Humphrey LL, et al. World health organization guidelines on treatment of hepatitis C virus infection: best practice advice from the American College of Physicians. Ann Intern Med. 2021;174:98-100.
Epclusa (sofosbuvir and velpatasvir) 400 mg/100 mg film-coated tablets. Summary of Product Characteristics. Gilead Sciences Ireland UC. 2020.
Chahine EB, Sucher AJ, Hemstreet BA. Sofosbuvir/velpatasvir: the first pangenotypic direct-acting antiviral combination for hepatitis C. Ann Pharmacother. 2017;51:44-53.
Buggisch P, Wursthorn K, Stoehr A, et al. Real-world effectiveness and safety of sofosbuvir/velpatasvir and ledipasvir/sofosbuvir hepatitis C treatment in a single centre in Germany. PLoS One. 2019;14:e0214795.
Charatcharoenwitthaya P, Wongpaitoon V, Komolmit P, et al. Real-world effectiveness and safety of sofosbuvir and nonstructural protein 5A inhibitors for chronic hepatitis C genotype 1, 2, 3, 4, or 6: a multicentre cohort study. BMC Gastroenterol. 2020;20:47.
Huang YT, Hsieh YY, Chen WM, et al. Sofosbuvir/velpatasvir is an effective treatment for patients with hepatitis C and advanced fibrosis or cirrhosis in a real-world setting in Taiwan. BMC Gastroenterol. 2021;21:259.
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;72:1112-1121.
Liu CH, Chen PY, Chen JJ, et al. Sofosbuvir/velpatasvir for patients with chronic hepatitis C virus infection and compensated liver disease: real-world data in Taiwan. Hepatol Int. 2021;15:338-349.
Mangia A, Milligan S, Khalili M, et al. Global real-world evidence of sofosbuvir/velpatasvir as simple, effective HCV treatment: analysis of 5552 patients from 12 cohorts. Liver Int. 2020;40:1841-1852.
Tada T, Kurosaki M, Nakamura S, et al. Real-world clinical outcomes of sofosbuvir and velpatasvir treatment in HCV genotype 1- and 2-infected patients with decompensated cirrhosis: a nationwide multicenter study by the Japanese Red Cross Liver Study Group. J Med Virol. 2021;93:6247-6256.
Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373:2599-2607.
Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med. 2015;373:2608-2617.
Epclusa (sofosbuvir and velpatasvir) tablets for oral use. Full Prescribing Information. Gilead Sciences, Inc.; 2021.
Wilton J, Wong S, Yu A, et al. Real-world effectiveness of sofosbuvir/velpatasvir for treatment of chronic hepatitis C in British Columbia, Canada: a population-based cohort study. Open Forum Infect Dis. 2020;7:ofaa055.
Younossi ZM, Stepanova M, Feld J, et al. Sofosbuvir/velpatasvir improves patient-reported outcomes in HCV patients: results from ASTRAL-1 placebo-controlled trial. J Hepatol. 2016;65:33-39.
Solomon SS, Wagner-Cardoso S, Smeaton L, et al. A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial. Lancet Gastroenterol Hepatol. 2022;7:307-317.
Andreoni M, Coppola N, Craxi A, et al. Meet-test-treat for HCV management: patients' and clinicians' preferences in hospital and drug addiction services in Italy. BMC Infect Dis. 2022;22:3.
Cunningham EB, Amin J, Feld JJ, et al. Adherence to sofosbuvir and velpatasvir among people with chronic HCV infection and recent injection drug use: the SIMPLIFY study. Int J Drug Policy. 2018;62:14-23.
Grebely J, Dalgard O, Conway B, et al. Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial. Lancet Gastroenterol Hepatol. 2018;3:153-161.
Grebely J, Feld JJ, Wyles D, et al. Sofosbuvir-based direct-acting antiviral therapies for HCV in people receiving opioid substitution therapy: an analysis of phase 3 studies. Open Forum Infect Dis. 2018;5:ofy001.