임영석 (울산대학교 의과대학)

한빛사논문

조회149

울산대학교 의과대학

CV File 220 kb

Lancet Gastroenterol. Hepatol., Jun 17 2024, S2468-1253(24)00096-7 | https://doi.org/10.1016/S2468-1253(24)00096-7 Switching to tenofovir alafenamide in patients with virologically suppressed chronic hepatitis B and renal or hepatic impairment: final week 96 results from an open-label, multicentre, phase 2 study

Prof Harry L A Janssen MD ^a,b†, Prof Young-Suk Lim MD ^c†, Prof Pietro Lampertico MD ^d,e, Prof Jeong Heo MD ^f, Chi-Yi Chen MD ^g, Claire Fournier MD ^h, Tak Yin Owen Tsang MD ⁱ, Ho Bae MD ^j, Chien-Hung Chen MD ^k, Prof Carla S Coffin MD ^l, Sang Hoon Ahn MD ^m, Huy Trinh MDⁿ, John F Flaherty PharmD ^o, Frida Abramov DMSc ^o, Yang Zhao PhD ^o, Yang Liu PhD^o, Audrey Lau MD ^o, Polina German PharmD ^o,p, Prof Wan-Long Chuang MD ^q, Kosh Agarwal MD ^r, Prof Edward Gane MD^s

^aDepartment of Gastroenterology and Hepatology, Erasmus MC University Hospital, Rotterdam, Netherlands

^bToronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada

^cAsan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

^dDivision of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

^eCRC “A. M. and A. Migliavacca” Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

^fDepartment of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea

^gChia-Yi Christian Hospital, Chia-Yi City, Taiwan

^hUniversité de Montréal, Montreal, QC, Canada

ⁱPrincess Margaret Hospital, Hong Kong Special Administrative Region, China

^jAsian Pacific Liver Center, St Vincent Medical Center, Los Angeles, CA, USA

^kKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, Taiwan

^lUniversity of Calgary, Calgary, AB, Canada

^mYonsei Liver Center, Severance Hospital, Seoul, South Korea

ⁿSan Jose Gastroenterology, San Jose, CA, USA

^oGilead Sciences, Foster City, CA, USA

^pCytokinetics, South San Francisco, CA, USA

^qKaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

^rKings College Hospital, London, UK

^sAuckland Clinical Studies, Grafton, New Zealand

^†Joint first authors

Correspondence to: Prof Harry L A Janssen

Abstract

Phase 3 studies in patients with chronic hepatitis B have shown tenofovir alafenamide to have non-inferior efficacy to tenofovir disoproxil fumarate, with improved renal and bone safety. We conducted this study to evaluate the safety and efficacy of switching to tenofovir alafenamide in participants with chronic hepatitis B and renal or hepatic impairment. This open-label, multicentre, phase 2 study was done in eight countries or territories at 30 sites. We recruited adults (≥18 years) with chronic hepatitis B who were virally suppressed on nucleoside or nucleotide analogues and had renal impairment (part A: moderate or severe in cohort 1 [estimated glomerular filtration rate by the Cockcroft-Gault formula (eGFR _CG) 15-59 mL/min] or end-stage renal disease [eGFR _CG <15 mL/min] on haemodialysis in cohort 2) or hepatic impairment including decompensation (part B: Child-Turcotte-Pugh score 7-12). Participants switched to 25 mg of tenofovir alafenamide given orally once daily for 96 weeks. The primary endpoint was the proportion of participants with viral suppression (HBV DNA <20 IU/mL) at week 24 by missing-equals-failure analysis. Efficacy (full analysis set) and safety (safety analysis set) analyses included all enrolled participants who received at least one dose of the study drug. Week 96 safety was assessed, including renal and bone parameters. This trial is registered at ClinicalTrials.gov, NCT03180619, and is completed. 124 participants (93 in part A [78 in cohort 1 and 15 in cohort 2] and 31 in part B) were enrolled between Aug 11, 2017, and Oct 17, 2018, and included in the full and safety analysis sets. 106 (85%) participants completed the study. There were 69 (74%) men and 24 (26%) women in part A and 21 (68%) men and ten (32%) women in part B. At week 24, 91 (97·8%, 95% CI 92·4 to 99·7) of 93 individuals in part A (76 [97·4%, 91·0 to 99·7] of 78 in cohort 1 and 15 [100·0%, 78·2 to 100·0] of 15 in cohort 2) and 31 (100·0%, 88·8 to 100·0) in part B had HBV DNA of less than 20 IU/mL. By week 96, the most common adverse event was upper respiratory tract infection, which occurred in 14 (15%) participants in part A and in six (19%) participants in part B. Serious adverse events occurred in 20 (22%) part A participants and in ten (32%) part B participants; none were related to treatment. No treatment-related deaths occurred. At week 96, median change in estimated glomerular filtration rate (Cockcroft-Gault method) was 1·0 mL/min (IQR -2·8 to 4·5) in cohort 1 and -2·4 mL/min (-11·4 to 10·7) in part B. Mean changes in spine and hip bone mineral density were 1·02% (SD 4·44) and 0·20% (3·25) in part A and -0·25% (3·91) and 0·28% (3·25) in part B. Tenofovir alafenamide might offer continued antiviral efficacy and a favourable safety profile for patients with renal or hepatic impairment and chronic hepatitis B switching from tenofovir disoproxil fumarate or other antivirals. Gilead Sciences.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-07-01)
연구진국내+국외 연구진
분야 의약학 > 응용의학

댓글 작성 로그인

CV 열람하기

연락처 보기