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标题: HBeAg 阳性慢性乙型肝炎患者从恩替卡韦转换为富马酸替诺福 [打印本页]

作者: StephenW 时间: 2021-12-22 07:07 标题: HBeAg 阳性慢性乙型肝炎患者从恩替卡韦转换为富马酸替诺福

HBeAg 阳性慢性乙型肝炎患者从恩替卡韦转换为富马酸替诺福韦地索普西：一项 4 期前瞻性研究
Fumitaka Suzuki 1, Yoshiyuki Suzuki 2, Yoshiyasu Karino 3 4, Yasuhito Tanaka 5 6, Masayuki Kurosaki 7, Hiroshi Yatsuhashi 8, Tomofumi Atarashi 9, Masanori Atsukawa 10, Tsunamasa Watanabe 11, Masaru Enomoto, Masaru Enomoto 1314 Hiroshi Kohno 15, Kouji Joko 16, Kojiro Michitaka 17, Koichiro Miki 18 19, Kazuhiro Takahashi 20, Tatsuya Ide 21, Shigetoshi Fujiyama 22, Tomoko Kohno 23, Hiroshi Itoh 23, Sakiyo Tsukawan Sakawan Yuauki 23, Kazuhiro Takahashi 23杉浦 25、熊田博光 2
隶属关系
隶属关系

1
Toranomon Hospital Kajigaya, 1-3-1, Kajigaya, Takatsu-ku, Kawasaki-city, Kanagawa, 213-8587, Japan。
2
Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, 105-8470, Japan。
3
Sapporo-Kosei General Hospital, 8-5, Kita 3-jo Higashi, Chuo-ku, 北海道, 札幌市, 060-0033, 日本.
四
Keiyukai Sapporo Hospital, 1-1, Kita, Hondori 14 chome, Shiroishi-ku, Sapporo-city, Hokkaido, 003-0027, Japan。
五
Nagoya City University Hospital, 1, Aza-Kawasumi, Mizuho, Nagoya, Aichi, 467-8602, Japan。
6
熊本大学，1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan。
7
武藏野红十字医院，1-26-1，京南町，武藏野市，东京，180-8610，日本。
8
National Hospital Organization Nagasaki Medical Center, 2-1001-1, Kubara, Omura-city, Nagasaki, 856-8562, Japan。
9
Obihiro-Kosei General Hospital, 10-1, Nishi 14-jo Minami, Obihiro-city, Hokkaido, 080-0024, Japan。
十
日本医科大学千叶北总医院，1715，镰仓，印西市，千叶，270-1694，日本。
11 11
圣玛丽安娜大学医学院医院，2-16-1, Sugao, Miyamae-ku, Kawasaki-city, Kanagawa, 216-8511, Japan。
12
大阪市立大学医院，1-5-7，Asahi-machi，Abeno-ku，Osaka-city，Osaka，545-8586，日本。
13
近代大学医院，377-2, Ohnohigashi, Osakasayama-city, Osaka, 589-8511, Japan。
14
Sanin Rosai 医院，1-8-1，Kaikeshinden，Yonago-city，Tottori，683-8605，日本。
15
国立医院组织吴医疗中心和中国癌症中心，3-1，青山町，吴市，广岛，广岛，737-0023，日本。
16 16
Matsuyama Red Cross Hospital, 1, Bunkyo-cho, Matsuyama-city, Ehime, 790-8524, Japan。
17 17
爱媛县中央医院，83，春日町，松山市，爱媛，790-0024，日本。
18 18
北九州市医院组织北九州市医疗中心，802-0077，日本福冈县北九州市小仓北区 Bashaku 2-1-1。
19 19
Shin-Eikai Hospital, 12-11, Bentencho, Kokurakita-ku, Kitakyushu-city, Fukuoka, 803-0856, Japan。
20
Hamanomachi Hospital, 3-3-1, Nagahama, Chuo-ku, Fukuoka-city, Fukuoka, 810-8539, Japan。
21
日本福冈市久留米市旭町 67 号久留米大学医院，邮编：830-0011。
22
熊本神道综合医院，3-2-65, Ooe, Chuo-ku, Chuo-ku, Kumamoto-city, Kumamoto, 862-8655, 日本。
二十三
GlaxoSmithKline K.K., Akasaka Intercity AIR, 1-8-1, Akasaka, Minato-ku, Tokyo, 107-0052, Japan。
24
GlaxoSmithKline K.K., Akasaka Intercity AIR, 1-8-1, Akasaka, Minato-ku, Tokyo, 107-0052, Japan. [email protected]。
二十五
国立全球健康与医学中心，1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan。

PMID：34930140 DOI：10.1186 / s12876-021-02008-9

抽象的

背景：富马酸替诺福韦二吡呋酯 (TDF) 被广泛使用并推荐作为乙型肝炎病毒 (HBV) 感染患者的一线治疗。然而，目前关于改用 TDF 治疗慢性疾病的有效性和安全性的数据有限。乙型肝炎 e 抗原 (HBeAg) 阳性患者的乙型肝炎病毒学被另一种核苷 (t) 类似物抑制。本研究的主要目的是评估从恩替卡韦转换后乙型肝炎表面抗原 (HBsAg) 的降低潜力(ETV) 至 48 周时 HBeAg 阳性慢性乙型肝炎患者血清 HBV-DNA 检测不到的 TDF。

方法：在这项多中心、单臂、开放标签、4 期临床研究中，目前使用 ETV 0.5 mg 每天一次治疗的 75 名参与者改用 TDF 300 mg 每天一次治疗，持续 96 周

结果：在第 48 周，3/74 名参与者 (4%) 的 HBsAg 水平从基线（主要终点）降低了 0.25 log10。平均 HBsAg 减少为 -0.14 log10 IU/mL，12% (9/74) 在 96 周时减少 0.25 log10。没有参与者达到 HBsAg 血清学清除。在丙氨酸转氨酶水平较高 (≥ 60 U/L) 的参与者中，HBsAg 在第 48 周和第 96 周的减少在数值上更大。 17 名参与者 (25%) 在第 96 周实现 HBeAg 血清清除。没有参与者经历病毒突破。所有与药物相关的不良事件（18 名参与者 [24%]）的强度都是轻微的，包括尿 β-2-微球蛋白增加（15 名参与者 [20%]）。

结论：总之，在该研究人群中，从 ETV 转换为 TDF 后 HBsAg 的减少是有限的。需要进一步调查以更好地了解从 ETV 转换为 TDF 的临床影响。 ClinicalTrials.gov：NCT03258710 于 2017 年 8 月 21 日注册。https://clinicaltrials.gov/ct2/s ... p;draw=2&rank=1。

关键词：慢性乙型肝炎；恩替卡韦； HBeAg 阳性；乙肝表面抗原；富马酸替诺福韦二吡呋酯。

© 2021。作者。

作者: StephenW 时间: 2021-12-22 07:08

Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study
Fumitaka Suzuki 1 , Yoshiyuki Suzuki 2 , Yoshiyasu Karino 3 4 , Yasuhito Tanaka 5 6 , Masayuki Kurosaki 7 , Hiroshi Yatsuhashi 8 , Tomofumi Atarashi 9 , Masanori Atsukawa 10 , Tsunamasa Watanabe 11 , Masaru Enomoto 12 , Masatoshi Kudo 13 , Naoto Maeda 14 , Hiroshi Kohno 15 , Kouji Joko 16 , Kojiro Michitaka 17 , Koichiro Miki 18 19 , Kazuhiro Takahashi 20 , Tatsuya Ide 21 , Shigetoshi Fujiyama 22 , Tomoko Kohno 23 , Hiroshi Itoh 23 , Sakiyo Tsukamoto 23 , Yuko Suzuki 23 , Yoshiaki Kawano 24 , Wataru Sugiura 25 , Hiromitsu Kumada 2
Affiliations
Affiliations

1
Toranomon Hospital Kajigaya, 1-3-1, Kajigaya, Takatsu-ku, Kawasaki-city, Kanagawa, 213-8587, Japan.
2
Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, 105-8470, Japan.
3
Sapporo-Kosei General Hospital, 8-5, Kita 3-jo Higashi, Chuo-ku, Sapporo-city, Hokkaido, 060-0033, Japan.
4
Keiyukai Sapporo Hospital, 1-1, Kita, Hondori 14 chome, Shiroishi-ku, Sapporo-city, Hokkaido, 003-0027, Japan.
5
Nagoya City University Hospital, 1, Aza-Kawasumi, Mizuho, Nagoya, Aichi, 467-8602, Japan.
6
Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
7
Musashino Red Cross Hospital, 1-26-1, Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan.
8
National Hospital Organization Nagasaki Medical Center, 2-1001-1, Kubara, Omura-city, Nagasaki, 856-8562, Japan.
9
Obihiro-Kosei General Hospital, 10-1, Nishi 14-jo Minami, Obihiro-city, Hokkaido, 080-0024, Japan.
10
Nippon Medical School Chiba Hokusoh Hospital, 1715, Kamakari, Inzai-City, Chiba, 270-1694, Japan.
11
St. Marianna University School of Medicine Hospital, 2-16-1, Sugao, Miyamae-ku, Kawasaki-city, Kanagawa, 216-8511, Japan.
12
Osaka City University Hospital, 1-5-7, Asahi-machi, Abeno-ku, Osaka-city, Osaka, 545-8586, Japan.
13
Kindai University Hospital, 377-2, Ohnohigashi, Osakasayama-city, Osaka, 589-8511, Japan.
14
Sanin Rosai Hospital, 1-8-1, Kaikeshinden, Yonago-city, Tottori, 683-8605, Japan.
15
National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1, Aoyama-cho, Kure-city, Hiroshima, 737-0023, Japan.
16
Matsuyama Red Cross Hospital, 1, Bunkyo-cho, Matsuyama-city, Ehime, 790-8524, Japan.
17
Ehime Prefectural Central Hospital, 83, Kasugamachi, Matsuyama-city, Ehime, 790-0024, Japan.
18
Kitakyushu City Hospital Organization Kitakyushu Municipal Medical Center, 2-1-1, Bashaku, Kokurakita-ku, Kitakyushu-city, Fukuoka, 802-0077, Japan.
19
Shin-Eikai Hospital, 12-11, Bentencho, Kokurakita-ku, Kitakyushu-city, Fukuoka, 803-0856, Japan.
20
Hamanomachi Hospital, 3-3-1, Nagahama, Chuo-ku, Fukuoka-city, Fukuoka, 810-8539, Japan.
21
Kurume University Hospital, 67, Asahi-machi, Kurume-shi, Fukuoka, 830-0011, Japan.
22
Kumamoto Shinto General Hospital, 3-2-65, Ooe, Chuo-ku, Kumamoto-city, Kumamoto, 862-8655, Japan.
23
GlaxoSmithKline K.K., Akasaka Intercity AIR, 1-8-1, Akasaka, Minato-ku, Tokyo, 107-0052, Japan.
24
GlaxoSmithKline K.K., Akasaka Intercity AIR, 1-8-1, Akasaka, Minato-ku, Tokyo, 107-0052, Japan. [email protected].
25
National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan.

PMID: 34930140 DOI: 10.1186/s12876-021-02008-9

Abstract

Background: Tenofovir 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.

Methods: In 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.

Results: At 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%]).

Conclusions: In 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/s ... ;draw=2&rank=1.

Keywords: Chronic hepatitis B; Entecavir; HBeAg-positive; HBsAg; Tenofovir disoproxil fumarate.

© 2021. The Author(s).

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