Switching to Besifovir in Patients with Chronic Hepatitis B Receiving Tenofovir Disoproxil Fumarate: A Randomized Trial

Yim, Hyung Joon; Seo, Yeon Seok; Kim, Ji Hoon; Kim, Won; Jung, Young Kul; Jang, Jae Young; Lee, Sae Hwan; Kim, Yun Soo; Kim, Chang Wook; Kim, Hyoung Su; Shim, Jae-Jun; Cho, Eun-Young; Kim, In Hee; Lee, Byung Seok; Lee, Jeong-Hoon; Kim, Byung Seok; Jang, Jeong Won; Lee, Hyun Woong; Kwon, Jung Hyun; Kim, Moon Young; Song, Do Seon; Park, Jung Gil; Lee, Yoon Seok; Yoon, Eileen L.; Lee, Han Ah; Kang, Seong Hee; Yang, Jin Mo

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Original Article

Switching to Besifovir in Patients with Chronic Hepatitis B Receiving Tenofovir Disoproxil Fumarate: A Randomized Trial

Hyung Joon Yim¹, Yeon Seok Seo², Ji Hoon Kim³, Won Kim⁴, Young Kul Jung¹, Jae Young Jang⁵, Sae Hwan Lee⁶, Yun Soo Kim⁷, Chang Wook Kim⁸, Hyoung Su Kim⁹, Jae-Jun Shim¹⁰, Eun-Young Cho¹¹, In Hee Kim¹², Byung Seok Lee¹³, Jeong-Hoon Lee¹⁴, Byung Seok Kim¹⁵, Jeong Won Jang¹⁶, Hyun Woong Lee¹⁷, Jung Hyun Kwon¹⁸, Moon Young Kim¹⁹, Do Seon Song²⁰, Jung Gil Park²¹, Yoon Seok Lee⁷, Eileen L. Yoon^22,23, Han Ah Lee²⁴, Seong Hee Kang¹, Jin Mo Yang²⁰

¹Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
²Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
³Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
⁴Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
⁵Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
⁶Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
⁷Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
⁸Department of Internal Medicine, Uijeongbu St.Mary's Hospital, The Catholic University of Korea, Seoul, Korea
⁹Internal Medicine, Kangdong Sacred Heart Hospital of Hallym University Medical Center, Seoul, Korea
¹⁰Department of Internal Medicine, Kyunghee University Hospital, Seoul, Korea
¹¹Department of Internal Medicine, Wonkwang University Hospital, Iksan, Korea
¹²Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, Korea
¹³Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea
¹⁴Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
¹⁵Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, Korea
¹⁶Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
¹⁷Department of Internal Medicine, Yonsei University Gangnam Severance Hospital, Seoul, Korea
¹⁸Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea
¹⁹Department of Internal Medicine, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea
²⁰Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea
²¹Department of Internal Medicine, Yeungnam University Hospital, Daegu, Korea
²²Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul, Korea
²³Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea
²⁴Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea

Correspondence :

Hyung Joon Yim ,
Tel: +82-31-412-6565, Fax: +82-31-412-5582, Email: gudwns21@korea.ac.kr
Jin Mo Yang ,
Tel: +82-31-249-8211, Fax: +82-31-253-8898, Email: jmyangdr@catholic.ac.kr

Received: September 19, 2024 Revised: November 27, 2024 Accepted: January 16, 2025

ABSTRACT

Background/Aims
Besifovir (BSV) showed comparable antiviral activity superior safety profiles to tenofovir disoproxil fumarate (TDF) in treatment-naïve chronic hepatitis B (CHB). However, no data are available regarding the antiviral efficacy and safety of BSV in patients with CHB who switched from long-term TDF to BSV. This study aimed to evaluate the outcome of a 48-week BSV therapy in patients with CHB who switched from long-term TDF treatment.
Methods
In this non-inferiority trial, 153 CHB patients treated with TDF for ≥48 weeks who had hepatitis B virus (HBV) DNA <20 IU/mL were randomized to receive either BSV 150 mg or TDF 300 mg for 48 weeks.
Results
The per-protocol analysis included 130 patients (BSV group, 64; TDF group, 66). The median duration of TDF use before enrollment was 4.14 years. After 48 weeks, 100.0% and 98.5% patients in the BSV and TDF groups, respectively, met the primary endpoint (HBV DNA <20 IU/mL), demonstrating the non-inferior antiviral efficacy of BSV to TDF (95% CI -0.01 to 0.04; P=1.000), with a predefined margin of -0.18. The mean percentage changes in estimated glomerular filtration rates were slightly better in the BSV group (1.67±11.73%) than in the TDF group (-1.24±11.02%). The BSV group showed a significant improvement in bone turnover biomarkers compared to the TDF group; accordingly, hip and spine bone mineral density increased in the BSV group.
Conclusions
In patients with CHB receiving long-term TDF, switching to BSV may improve renal and bone safety with non-inferior antiviral efficacy compared to that of maintaining TDF. ClinicalTrials.gov Identifier: NCT04202536

KeyWords: Antiviral therapy; Hepatitis B; Bone mineral density; Nephrotoxicity; Sustained Virologic Response