Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study

BMC Gastroenterology

Kojiro Michitaka¹  Yuko Suzuki²  Tomoko Kohno²  Yoshiaki Kawano²  Hiroshi Itoh²  Sakiyo Tsukamoto²  Kazuhiro Takahashi³  Masatoshi Kudo⁴  Koichiro Miki⁵  Shigetoshi Fujiyama⁶  Tatsuya Ide⁷  Kouji Joko⁸  Masayuki Kurosaki⁹  Yasuhito Tanaka^1,10  Wataru Sugiura^1,11  Hiroshi Kohno^1,12  Hiroshi Yatsuhashi^1,13  Masanori Atsukawa^1,14  Tomofumi Atarashi^1,15  Masaru Enomoto^1,16  Naoto Maeda^1,17  Yoshiyasu Karino^1,18  Tsunamasa Watanabe^1,19  Fumitaka Suzuki^2,20  Yoshiyuki Suzuki^2,21  Hiromitsu Kumada^2,21 

[1] Ehime Prefectural Central Hospital, 83, Kasugamachi, 790-0024, Matsuyama-city, Ehime, Japan;GlaxoSmithKline K.K., Akasaka Intercity AIR, 1-8-1, Akasaka, Minato-ku, 107-0052, Tokyo, Japan;Hamanomachi Hospital, 3-3-1, Nagahama, Chuo-ku, 810-8539, Fukuoka-city, Fukuoka, Japan;Kindai University Hospital, 377-2, Ohnohigashi, 589-8511, Osakasayama-city, Osaka, Japan;Kitakyushu City Hospital Organization Kitakyushu Municipal Medical Center, 2-1-1, Bashaku, Kokurakita-ku, 802-0077, Kitakyushu-city, Fukuoka, Japan;Shin-Eikai Hospital, 12-11, Bentencho, Kokurakita-ku, 803-0856, Kitakyushu-city, Fukuoka, Japan;Kumamoto Shinto General Hospital, 3-2-65, Ooe, Chuo-ku, 862-8655, Kumamoto-city, Kumamoto, Japan;Kurume University Hospital, 67, Asahi-machi, Kurume-shi, 830-0011, Fukuoka, Japan;Matsuyama Red Cross Hospital, 1, Bunkyo-cho, 790-8524, Matsuyama-city, Ehime, Japan;Musashino Red Cross Hospital, 1-26-1, Kyonan-cho, Musashino-shi, 180-8610, Tokyo, Japan;Nagoya City University Hospital, 1, Aza-Kawasumi, Mizuho, 467-8602, Nagoya, Aichi, Japan;Kumamoto University, 1-1-1 Honjo, Chuo-ku, 860-8556, Kumamoto, Japan;National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, 162-8655, Tokyo, Japan;National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1, Aoyama-cho, 737-0023, Kure-city, Hiroshima, Japan;National Hospital Organization Nagasaki Medical Center, 2-1001-1, Kubara, 856-8562, Omura-city, Nagasaki, Japan;Nippon Medical School Chiba Hokusoh Hospital, 1715, Kamakari, 270-1694, Inzai-City, Chiba, Japan;Obihiro-Kosei General Hospital, 10-1, Nishi 14-jo Minami, 080-0024, Obihiro-city, Hokkaido, Japan;Osaka City University Hospital, 1-5-7, Asahi-machi, Abeno-ku, 545-8586, Osaka-city, Osaka, Japan;Sanin Rosai Hospital, 1-8-1, Kaikeshinden, 683-8605, Yonago-city, Tottori, Japan;Sapporo-Kosei General Hospital, 8-5, Kita 3-jo Higashi, Chuo-ku, 060-0033, Sapporo-city, Hokkaido, Japan;Keiyukai Sapporo Hospital, 1-1, Kita, Hondori 14 chome, Shiroishi-ku, 003-0027, Sapporo-city, Hokkaido, Japan;St. Marianna University School of Medicine Hospital, 2-16-1, Sugao, Miyamae-ku, 216-8511, Kawasaki-city, Kanagawa, Japan;Toranomon Hospital Kajigaya, 1-3-1, Kajigaya, Takatsu-ku, 213-8587, Kawasaki-city, Kanagawa, Japan;Toranomon Hospital, 2-2-2, Toranomon, 105-8470, Minato-ku, Japan;

关键词: Tenofovir disoproxil fumarate;    Chronic hepatitis B;    HBsAg;    HBeAg-positive;    Entecavir;   

DOI  :  10.1186/s12876-021-02008-9

来源: Springer

【 摘 要 】

BackgroundTenofovir disoproxil fumarate (TDF) is widely used and recommended as first-line treatment for patients infected with the hepatitis B virus (HBV). However, current data are limited regarding the efficacy and safety of switching to TDF for the treatment of chronic hepatitis B in hepatitis B e-antigen (HBeAg)-positive patients who are virologically suppressed with another nucleos(t)ide analogue. The primary objective of this study was to evaluate the hepatitis B surface antigen (HBsAg) reduction potential of switching from entecavir (ETV) to TDF at week 48 in HBeAg-positive chronic hepatitis B patients with undetectable serum HBV-DNA.MethodsIn this multicenter, single-arm, open-label, phase 4 clinical study, 75 participants currently treated with ETV 0.5 mg once daily were switched to TDF 300 mg once daily for 96 weeks.ResultsAt week 48, 3/74 participants (4%) achieved 0.25 log10 reduction of HBsAg levels from baseline (the primary endpoint). Mean HBsAg reduction was −0.14 log10 IU/mL and 12% (9/74) achieved 0.25 log10 reduction by 96 weeks. No participants achieved HBsAg seroclearance. HBsAg reduction at weeks 48 and 96 was numerically greater in participants with higher alanine aminotransferase levels (≥ 60 U/L). Seventeen participants (25%) achieved HBeAg seroclearance up to week 96. No participants experienced viral breakthrough. All drug-related adverse events (18 participants [24%]) were mild in intensity, including an increase in urine beta-2-microglobulin (15 participants [20%]).ConclusionsIn conclusion, HBsAg reduction was limited after switching from ETV to TDF in this study population. Further investigation is warranted to better understand the clinical impact of switching from ETV to TDF.ClinicalTrials.gov: NCT03258710 registered August 21, 2017. https://clinicaltrials.gov/ct2/show/NCT03258710?term=NCT03258710&draw=2&rank=1

【 授权许可】

CC BY