Eight-year efficacy and safety of tenofovir alafenamide for treatment of chronic hepatitis B virus infection: Final results from two randomised phase 3 trials.

Autor: Buti M; Hospital Universitario Vall d'Hebron, Barcelona, Spain.; CIBEREHD del Instituto Carlos III, Madrid, Spain., Lim YS; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea., Chan HLY; 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., Chuang WL; Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan., Janssen HLA; Erasmus Medical Center, Rotterdam, Netherlands and Department of Medicine, University of Toronto, Toronto, Ontario, Canada., Fung SK; Department of Medicine, University of Toronto, Toronto, Ontario, Canada., Izumi N; Department of Gastroenterology and Hepatology, Japanese Red Cross Musashino Hospital, Tokyo, Japan., Jablkowski MS; Medical University of Łódź, Łódź, Poland., Abdurakhmanov D; Sechenov University, Moscow, Russia., Abramov F; Gilead Sciences, Inc., Foster City, California, USA., Wang H; Gilead Sciences, Inc., Foster City, California, USA., Botros I; Gilead Sciences, Inc., Foster City, California, USA., Yee LJ; Gilead Sciences, Inc., Foster City, California, USA., Mateo R; Gilead Sciences, Inc., Foster City, California, USA., Flaherty JF; Gilead Sciences, Inc., Foster City, California, USA., Osinusi A; Gilead Sciences, Inc., Foster City, California, USA., Pan CQ; NYU Langone Health, New York University Grossman School of Medicine, New York, New York, USA., Shalimar X; All India Institute of Medical Sciences, New Delhi, India., Seto WK; Department of Medicine and School of Clinical Medicine, The University of Hong Kong, Hong Kong., Gane EJ; University of Auckland, Auckland, New Zealand.
Jazyk: angličtina
Zdroj: Alimentary pharmacology & therapeutics [Aliment Pharmacol Ther] 2024 Dec; Vol. 60 (11-12), pp. 1573-1586. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1111/apt.18278
Abstrakt: 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; eGFR CG ) 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 eGFR CG 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.
(© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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