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Clin Gastroenterol Hepatol. 2018 Jun 20. pii: S1542-3565(18)30633-5. doi: 10.1016/j.cgh.2018.06.023. [Epub ahead of print]

Improved Bone Safety of Tenofovir Alafenamide Compared to Tenofovir Disoproxil Fumarate Over 2 Years in Patients With Chronic HBV Infection.

Author information

1
Department of Medicine, The University of Hong Kong, Hong Kong. Electronic address: wkseto@hku.hk.
2
Department of Gastroenterology and Hepatology and Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan.
3
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
4
Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
5
Institute of Gastroenterology and Hepatology, University of Medicine and Pharmacy "Grigore T. Popa," Iasi, Romania.
6
Sechenov First Moscow State Medical University, Moscow, Russia.
7
Deparment of Infectious Diseases, Istanbul University, Cerrahpasa School of Medicine, Istanbul, Turkey.
8
Research and Education, Inc, San Diego, California.
9
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
10
Department of Gastroenterology, Kobe City Medical Center General Hospital, Kobe, Japan.
11
Department of Gastroenterology, Okayama University Hospital, Okayama, Japan.
12
Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Foggia, Fogia, Italy.
13
Pôle Hépato-digestif, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Institut Hospitalo-Universitaire, Inserm U 1110, Institut sur les Maladies Virales et Hépatiques, Université de Strasbourg, Strasbourg, France.
14
Gastrointestinal Research Institute, Vancouver, British Columbia, Canada.
15
Gilead Sciences, Foster City, California.
16
Midas Multispecialty Hospital, Nagpur, India.
17
Clinical and Experimental Medicine Department, University of Pisa, Pisa, Italy.
18
Toronto General Hospital, Toronto, Ontario, Canada.
19
Department of Medicine & Therapeutics, Prince of Wales Hospital, Hong Kong, Hong Kong.

Abstract

BACKGROUND & AIMS:

Long-term use of tenofovir disoproxil fumarate (TDF) reduces bone mineral density (BMD). Tenofovir alafenamide (TAF), a new prodrug of tenofovir, has shown non-inferior efficacy to TDF in patients with chronic hepatitis B virus (HBV) infection, with improved bone effects at 48 weeks. We performed a randomized trial to evaluate the bone safety of TAF compared with TDF over 2 years, assessing baseline risk factors for bone loss, were evaluated after 2 years of treatment.

METHODS:

In a double-blind study, hepatitis B e antigen (HBeAg)-positive patients (n = 873) and HBeAg-negative patients (n = 425) were randomly assigned (2:1) to groups given TAF (25 mg; n = 866) or TDF (300 mg; n = 432) once daily. We assessed bone safety, including hip and spine BMD, using dual-energy X-ray absorptiometry and measured changes in serum markers of bone turnover over 96 weeks.

RESULTS:

At baseline, treatment groups were well matched. At week 96, patients receiving TAF had significantly smaller decreases in hip BMD (mean reduction of 0.33%) than patients receiving TDF (mean reduction of 2.51%) (P < .001) and spine BMD (reduction of 0.75% in patients receiving patients receiving TAF vs reduction of 2.57% in patients receiving TDF) (P < .001). For hip BMD, the magnitude of difference in bone loss between the TAF and TDF groups increased at week 96 compared to week 48 (P < .001). The TAF group had minimal changes in markers of bone turnover by 12 weeks of treatment, but the TDF group had significant changes, compared to baseline. Risk factors for bone loss had fewer effects in patients receiving TAF than TDF at week 96.

CONCLUSIONS:

In double-blind randomized trials, we found that after 2 years of treatment, patients receiving TAF had continued improvements in bone safety compared with patients receiving TDF. Clinicaltrial.gov ID NCT01940471 and NCT01940341.

KEYWORDS:

CHB; Nucleoside Analogues; Osteoporosis; Side Effect

PMID:
29933096
DOI:
10.1016/j.cgh.2018.06.023

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