Sistema de Salut de Catalunya
Institut Català de la Salut
[Buti M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBEREHD del Instituto Carlos III, Madrid, Spain. [Lim YS] Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. [Lik Yuen Chan H] Faculty of Medicine, The Chinese University of Hong Kong, HMA Office, Tai Wai, Shatin, Hong Kong. [Agarwal K] Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK. [Marcellin P] Hepatology Department, Hôpital Beaujon, APHP, INSERM, University of Paris, Clichy, France. [Brunetto MR] Department of Clinical and Experimental Medicine, University of Pisa and Hepatology Unit, Pisa University Hospital, Pisa, Italy
Vall d'Hebron Barcelona Hospital Campus
2024-12-27T10:52:53Z
2024-12-27T10:52:53Z
2024-12
Efficacy; Chronic infection; Hepatitis B virus
Eficacia; Infección crónica; Virus de la hepatitis B
Eficàcia; Infecció crònica; Virus de l'hepatitis B
Background In two phase 3 studies, tenofovir alafenamide (TAF) showed non-inferior efficacy versus tenofovir disoproxil fumarate (TDF), with more favourable renal and bone safety in patients with chronic hepatitis B (CHB). Aims Here, we report the studies' final 8-year results. Methods CHB patients (hepatitis B e antigen [HBeAg]-negative and HBeAg-positive) were randomised (2:1) to double-blind TAF 25 mg/day or TDF 300 mg/day for up to 3 years, followed by open-label (OL) TAF through year 8. Virological, biochemical, serological and fibrosis responses, and safety, including bone and renal parameters, were evaluated. Resistance to TAF was assessed annually by deep sequencing of polymerase/reverse transcriptase and by phenotyping. Results Among 1298 patients randomised to double-blind TAF (n = 866) or double-blind TDF (n = 432), 775 in the TAF group and 382 in the TDF group received OL TAF, including 180 and 202 who switched from TDF to TAF at year 2 (TDF2y → TAF6y) or year 3 (TDF3y → TAF5y), respectively. At year 8, among patients in the TAF8y, TDF2y → TAF6y and TDF3y → TAF5y groups, 69%, 66% and 73% (missing-equals-failure analysis) and 95%, 94% and 97% (missing-equals-excluded) of patients, respectively, achieved HBV DNA <29 IU/mL. Estimated glomerular filtration rate (Cockcroft-Gault method; eGFRCG) and hip/spine bone mineral density (BMD) remained stable in patients receiving double-blind/OL TAF, with only small declines at year 8. Decreases in eGFRCG and hip/spine BMD observed during double-blind TDF improved after switching to OL TAF. No patients developed resistance to TAF. Conclusion Long-term TAF treatment exhibited favourable safety and tolerability with high rates of viral suppression and no development of resistance. ClinicalTrials.gov numbers NCT01940341 and NCT01940471.
These studies were funded by Gilead Sciences, Inc.
Article
Published version
English
Avaluació de resultats (Assistència sanitària); Hepatitis B - Tractament; Medicaments antivírics - Ús terapèutic; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents; Other subheadings::Other subheadings::/therapeutic use; DISEASES::Virus Diseases::Virus Diseases::Hepatitis, Viral, Human::Hepatitis B::Hepatitis B, Chronic; Other subheadings::Other subheadings::Other subheadings::/drug therapy; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos; Otros calificadores::Otros calificadores::/uso terapéutico; ENFERMEDADES::virosis::virosis::hepatitis viral humana::hepatitis B::hepatitis B crónica; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
Wiley
Alimentary Pharmacology & Therapeutics;60(11-12)
https://doi.org/10.1111/apt.18278
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
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