483
EFFICACY AND SAFETY OF SWITCHING TO TENOFOVIR
ALAFENAMIDE (TAF) IN VIRALLY SUPPRESSED CHRONIC
HEPATITIS B (CHB) PATIENTS WITH RENAL IMPAIRMENT:
WEEK 24 RESULTS FROM A PHASE 2 OPEN-LABEL STUDY
Harry L. A. Janssen1, Young-Suk LIM2, Edward J. Gane3,
Claire Fournier4, Sang Hoon Ahn5, Owen Tsang6, Wan Long
Chuang7, Jeong Heo8, Aric Josun Hui9, Magdy Elkhashab10,
Chi-Yi Chen11, Wei-Wen Su12, John F Flaherty13, Anuj
Gaggar14, Susanna Tan15, Audrey H Lau16, Vithika Suri16,
Shuyuan Mo16, Mani Subramanian13, Syed-Mohammed Jafri17,
Kosh Agarwal18, Pietro Lampertico19, Giulo Marchesini20,
Carla S. Coffin21 and Yi-Hsiang Huang22, (1)Toronto Centre
for Liver Disease, Toronto General Hospital, University
Health Network, (2)Gastroenterology, Asan Medical Center,
University of Ulsan College of Medicine, Seoul, Republic of
Korea, (3)Auckland Clinical Studies, Auckland, New Zealand,
(4)CHUM, Service D’hépatologie, Montreal, Canada, (5)
Yonsei Liver Center, Severance Hospital, (6)Princess
Margaret Hospital, 2-10 Princess Margaret Hospital Rd,
Kwai Chung, Hong Kong, (7)Kaohsiung Medical University
Hospital, Kaohsiung, Taiwan, (8)Medical Research Institute,
Pusan National University Hospital, Busan, Korea, (9)Alice
Ho Miu Ling Nethersole Hospital, (10)Research, Toronto
Liver Centre, (11)Department of Internal Medicine, Chia-Yi
Christian Hospital, Chia-Yi, Taiwan, (12)Changhua Christian
Hospital, Changhua, Taiwan, (13)Gilead Sciences, Inc., (14)
Gilead Sciences Inc., Foster City, CA, (15)Gilead Sciences,
Inc, Foster City, California, USA,, (16)Gilead Sciences, Inc,
Foster City, California, USA, (17)Gastroenterology, Henry
Ford Hospital, (18)Institute of Liver Studies, King’s College
Hospital, (19)Gastroenterology and Hepatology, Fondazione
Irccs Ca’ Granda O. Maggiore Policlinico, University of
Milan, (20)University of Bologna, (21)Medicine, University of
Calgary, (22)Division of Gastroenterology and Hepatology,
Department of Medicine, Taipei Veterans General Hospital
Background: TAF, a novel tenofovir prodrug, has
demonstrated noninferior efficacy to tenofovir disoproxil
fumurate (TDF) with superior bone and renal safety in virally
suppressed CHB patients with eGFR (by Cockcroft-Gault;
eGFRCG) ≥50 mL/min when switched from TDF. Efficacy
and safety of virally suppressed patients on TDF with renal
impairment who were switched to TAF were evaluated in this
Phase 2 study Methods: CHB patients with renal impairment
receiving TDF for ≥48 weeks and virally suppressed for ≥6
months with HBV DNA <20 IU/mL at screening were enrolled
into 2 cohorts: 1) moderate-severe renal impairment (eGFRCG
15 to <60mL/min) and 2) end stage renal disease (ESRD)
(eGFRCG <15 mL/min) on chronic hemodialysis (HD) All
patients were switched to TAF 25 mg once daily for 96 weeks
Co-primary endpoints were proportion with HBV DNA <20 IU/
mL and graded adverse events (AEs)/lab abnormalities at
Week 24. Key secondary safety endpoints were changes in
hip and spine bone mineral density (BMD) and serum markers
of bone turnover (Table), as well as changes in eGFRCG
and urinary markers of tubular function (mod-severe renal
impairment group only) Results: 93 patients (moderatesevere
impairment 78; ESRD 15) were enrolled from 26 sites
in 8 countries Median age was 65 years, 74% male, 77%
Asian, 83% HBeAg-negative, up to 60% had low BMD at hip
and/or spine, and 60% and 24% had a history of hypertension
and/or diabetes mellitus, respectively. Key efficacy/safety
results at Week 24 are summarized in the Table. All patients
on treatment at Week 24 maintained HBV DNA <20 IU/mL and
a high proportion had normal ALT levels Relative to baseline
levels, switching to TAF from TDF resulted in increases in
hip and spine BMD, decreases in bone turnover markers,
as well as an increase in eGFRCG and improved markers of
renal tubular function TAF was well tolerated with few having
Grade 3 or 4 AEs (7 5%); no serious AEs related to study drug
and no discontinuations due to AEs Conclusion: In renallyimpaired
CHB patients, including ESRD patients on HD, viral
suppression was well maintained and the bone and renal
safety were improved 24 weeks after switching from TDF to
TAF. 作者: StephenW 时间: 2019-10-29 19:42