Cargando…

Efficacy and Safety of Tenofovir Disoproxil Orotate in Chronic Hepatitis B Patients Previously Treated with Tenofovir Disoproxil Fumarate: Multicenter, Open-Label, Prospective Study

Background/Aim: We aimed to demonstrate the efficacy and safety of tenofovir disoproxilorotate (TDO) compared with that of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B. Methods: This multicenter, open-label, prospective clinical trial (KCT0004185) was conducted to evaluat...

Descripción completa

Detalles Bibliográficos
Autores principales: Chang, Young, Kim, Sang-Gyune, Jeong, Soung-Won, Jang, Jae-Young, Yoo, Jeong-Ju, Lee, Sae-Hwan, Kim, Young-Seok, Kim, Hong-Soo, Lee, Hyun-Woong, Park, Suyeon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658686/
https://www.ncbi.nlm.nih.gov/pubmed/34884330
http://dx.doi.org/10.3390/jcm10235628
_version_ 1784612788958658560
author Chang, Young
Kim, Sang-Gyune
Jeong, Soung-Won
Jang, Jae-Young
Yoo, Jeong-Ju
Lee, Sae-Hwan
Kim, Young-Seok
Kim, Hong-Soo
Lee, Hyun-Woong
Park, Suyeon
author_facet Chang, Young
Kim, Sang-Gyune
Jeong, Soung-Won
Jang, Jae-Young
Yoo, Jeong-Ju
Lee, Sae-Hwan
Kim, Young-Seok
Kim, Hong-Soo
Lee, Hyun-Woong
Park, Suyeon
author_sort Chang, Young
collection PubMed
description Background/Aim: We aimed to demonstrate the efficacy and safety of tenofovir disoproxilorotate (TDO) compared with that of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B. Methods: This multicenter, open-label, prospective clinical trial (KCT0004185) was conducted to evaluate the efficacy and safety of TDO on switching from TDF for 24 weeks in virologically suppressed chronic hepatitis B patients. The primary efficacy endpoint was the maintenance of virologic response. Safety was assessed by evaluating major adverse events, changes in renal function, and occurrence of hepatocellular carcinoma (HCC). Results: TDO treatment was not inferior in terms of virological response when compared with that on TDF treatment, with a noninferiority margin of −10% (risk difference, −3.17%; 95% confidence interval, −7.5–1.15%). The biological response of TDO was also comparable to that of TDF, with no significant difference in the proportion of patients with normalized alanine transaminase levels. After 24 weeks of treatment, hepatitis B core-related antigen (HBcrAg) significantly decreased to a mean titer of 3.91 log U/mL from 4.15 log U/mL at baseline (p = 0.01). There were no cases of grade 3 or higher adverse events and HCC. The mean estimated glomerular filtration rate increased from 91.09 mL/min to 93.34 mL/min (p = 0.056), and the mean serum level of phosphorus increased from 3.33 mg/dL to 3.44 mg/dL (p = 0.045), suggesting improvement in renal function with TDO treatment. Conclusion: In patients with chronic hepatitis B, the efficacy of TDO was noninferior to that of TDF, with a significant decrease in the HBcrAg titer and improved renal function.
format Online
Article
Text
id pubmed-8658686
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-86586862021-12-10 Efficacy and Safety of Tenofovir Disoproxil Orotate in Chronic Hepatitis B Patients Previously Treated with Tenofovir Disoproxil Fumarate: Multicenter, Open-Label, Prospective Study Chang, Young Kim, Sang-Gyune Jeong, Soung-Won Jang, Jae-Young Yoo, Jeong-Ju Lee, Sae-Hwan Kim, Young-Seok Kim, Hong-Soo Lee, Hyun-Woong Park, Suyeon J Clin Med Article Background/Aim: We aimed to demonstrate the efficacy and safety of tenofovir disoproxilorotate (TDO) compared with that of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B. Methods: This multicenter, open-label, prospective clinical trial (KCT0004185) was conducted to evaluate the efficacy and safety of TDO on switching from TDF for 24 weeks in virologically suppressed chronic hepatitis B patients. The primary efficacy endpoint was the maintenance of virologic response. Safety was assessed by evaluating major adverse events, changes in renal function, and occurrence of hepatocellular carcinoma (HCC). Results: TDO treatment was not inferior in terms of virological response when compared with that on TDF treatment, with a noninferiority margin of −10% (risk difference, −3.17%; 95% confidence interval, −7.5–1.15%). The biological response of TDO was also comparable to that of TDF, with no significant difference in the proportion of patients with normalized alanine transaminase levels. After 24 weeks of treatment, hepatitis B core-related antigen (HBcrAg) significantly decreased to a mean titer of 3.91 log U/mL from 4.15 log U/mL at baseline (p = 0.01). There were no cases of grade 3 or higher adverse events and HCC. The mean estimated glomerular filtration rate increased from 91.09 mL/min to 93.34 mL/min (p = 0.056), and the mean serum level of phosphorus increased from 3.33 mg/dL to 3.44 mg/dL (p = 0.045), suggesting improvement in renal function with TDO treatment. Conclusion: In patients with chronic hepatitis B, the efficacy of TDO was noninferior to that of TDF, with a significant decrease in the HBcrAg titer and improved renal function. MDPI 2021-11-29 /pmc/articles/PMC8658686/ /pubmed/34884330 http://dx.doi.org/10.3390/jcm10235628 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Young
Kim, Sang-Gyune
Jeong, Soung-Won
Jang, Jae-Young
Yoo, Jeong-Ju
Lee, Sae-Hwan
Kim, Young-Seok
Kim, Hong-Soo
Lee, Hyun-Woong
Park, Suyeon
Efficacy and Safety of Tenofovir Disoproxil Orotate in Chronic Hepatitis B Patients Previously Treated with Tenofovir Disoproxil Fumarate: Multicenter, Open-Label, Prospective Study
title Efficacy and Safety of Tenofovir Disoproxil Orotate in Chronic Hepatitis B Patients Previously Treated with Tenofovir Disoproxil Fumarate: Multicenter, Open-Label, Prospective Study
title_full Efficacy and Safety of Tenofovir Disoproxil Orotate in Chronic Hepatitis B Patients Previously Treated with Tenofovir Disoproxil Fumarate: Multicenter, Open-Label, Prospective Study
title_fullStr Efficacy and Safety of Tenofovir Disoproxil Orotate in Chronic Hepatitis B Patients Previously Treated with Tenofovir Disoproxil Fumarate: Multicenter, Open-Label, Prospective Study
title_full_unstemmed Efficacy and Safety of Tenofovir Disoproxil Orotate in Chronic Hepatitis B Patients Previously Treated with Tenofovir Disoproxil Fumarate: Multicenter, Open-Label, Prospective Study
title_short Efficacy and Safety of Tenofovir Disoproxil Orotate in Chronic Hepatitis B Patients Previously Treated with Tenofovir Disoproxil Fumarate: Multicenter, Open-Label, Prospective Study
title_sort efficacy and safety of tenofovir disoproxil orotate in chronic hepatitis b patients previously treated with tenofovir disoproxil fumarate: multicenter, open-label, prospective study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658686/
https://www.ncbi.nlm.nih.gov/pubmed/34884330
http://dx.doi.org/10.3390/jcm10235628
work_keys_str_mv AT changyoung efficacyandsafetyoftenofovirdisoproxilorotateinchronichepatitisbpatientspreviouslytreatedwithtenofovirdisoproxilfumaratemulticenteropenlabelprospectivestudy
AT kimsanggyune efficacyandsafetyoftenofovirdisoproxilorotateinchronichepatitisbpatientspreviouslytreatedwithtenofovirdisoproxilfumaratemulticenteropenlabelprospectivestudy
AT jeongsoungwon efficacyandsafetyoftenofovirdisoproxilorotateinchronichepatitisbpatientspreviouslytreatedwithtenofovirdisoproxilfumaratemulticenteropenlabelprospectivestudy
AT jangjaeyoung efficacyandsafetyoftenofovirdisoproxilorotateinchronichepatitisbpatientspreviouslytreatedwithtenofovirdisoproxilfumaratemulticenteropenlabelprospectivestudy
AT yoojeongju efficacyandsafetyoftenofovirdisoproxilorotateinchronichepatitisbpatientspreviouslytreatedwithtenofovirdisoproxilfumaratemulticenteropenlabelprospectivestudy
AT leesaehwan efficacyandsafetyoftenofovirdisoproxilorotateinchronichepatitisbpatientspreviouslytreatedwithtenofovirdisoproxilfumaratemulticenteropenlabelprospectivestudy
AT kimyoungseok efficacyandsafetyoftenofovirdisoproxilorotateinchronichepatitisbpatientspreviouslytreatedwithtenofovirdisoproxilfumaratemulticenteropenlabelprospectivestudy
AT kimhongsoo efficacyandsafetyoftenofovirdisoproxilorotateinchronichepatitisbpatientspreviouslytreatedwithtenofovirdisoproxilfumaratemulticenteropenlabelprospectivestudy
AT leehyunwoong efficacyandsafetyoftenofovirdisoproxilorotateinchronichepatitisbpatientspreviouslytreatedwithtenofovirdisoproxilfumaratemulticenteropenlabelprospectivestudy
AT parksuyeon efficacyandsafetyoftenofovirdisoproxilorotateinchronichepatitisbpatientspreviouslytreatedwithtenofovirdisoproxilfumaratemulticenteropenlabelprospectivestudy