Entecavir+tenofovir vs. Lamivudine/telbivudine+ adefovir in chronic hepatitis b patients with prior suboptimal response

Hyun Young Woo; Jun Yong Park; Si Hyun Bae; Chang Wook Kim; Jae Young Jang; Won Young Tak; Dong Joon Kim; In Hee Kim; Jeong Heo; Sang Hoon Ahn

doi:10.3350/cmh.2019.0044n

Entecavir+tenofovir vs. Lamivudine/telbivudine+ adefovir in chronic hepatitis b patients with prior suboptimal response

Hyun Young Woo, Jun Yong Park, Si Hyun Bae, Chang Wook Kim, Jae Young Jang, Won Young Tak, Dong Joon Kim, In Hee Kim, Jeong Heo, Sang Hoon Ahn

Department of Internal Medicine

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Abstract

Background/Aims: Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV. Methods: This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded. Results: Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs.-0.37 log₁₀ IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV-or ETVassociated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/ LdT+ADV group (P=0.106). The two groups had similar rates of adverse events. Conclusions: ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/ LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).

Original language	English
Pages (from-to)	352-363
Number of pages	12
Journal	Clinical and Molecular Hepatology
Volume	26
Issue number	3
DOIs	https://doi.org/10.3350/cmh.2019.0044n
Publication status	Published - 2020 Jul

Bibliographical note

Funding Information:
This investigator-initiated trial was supported by an unrestricted grant from Bristol-Myers Squibb (BMS) and clinical research grant from Pusan National University Hospital in 2018. BMS had no role in the study design and the authors retain full responsibility for the collection and interpretation of data, decision to publish, and preparation of the manuscript.

Publisher Copyright:
© 2020 by Korean Association for the Study of the Liver.

All Science Journal Classification (ASJC) codes

Hepatology
Molecular Biology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3350/cmh.2019.0044n

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@article{69808be7154b493a9d6a5fcb33de250e,

title = "Entecavir+tenofovir vs. Lamivudine/telbivudine+ adefovir in chronic hepatitis b patients with prior suboptimal response",

abstract = "Background/Aims: Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV. Methods: This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded. Results: Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs.-0.37 log10 IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV-or ETVassociated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/ LdT+ADV group (P=0.106). The two groups had similar rates of adverse events. Conclusions: ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/ LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).",

author = "Woo, {Hyun Young} and Park, {Jun Yong} and Bae, {Si Hyun} and Kim, {Chang Wook} and Jang, {Jae Young} and Tak, {Won Young} and Kim, {Dong Joon} and Kim, {In Hee} and Jeong Heo and Ahn, {Sang Hoon}",

note = "Funding Information: This investigator-initiated trial was supported by an unrestricted grant from Bristol-Myers Squibb (BMS) and clinical research grant from Pusan National University Hospital in 2018. BMS had no role in the study design and the authors retain full responsibility for the collection and interpretation of data, decision to publish, and preparation of the manuscript. Publisher Copyright: {\textcopyright} 2020 by Korean Association for the Study of the Liver.",

year = "2020",

month = jul,

doi = "10.3350/cmh.2019.0044n",

language = "English",

volume = "26",

pages = "352--363",

journal = "Clinical and molecular hepatology",

issn = "2287-2728",

publisher = "Korean Association for the Study of the Liver",

number = "3",

}

TY - JOUR

T1 - Entecavir+tenofovir vs. Lamivudine/telbivudine+ adefovir in chronic hepatitis b patients with prior suboptimal response

AU - Woo, Hyun Young

AU - Park, Jun Yong

AU - Bae, Si Hyun

AU - Kim, Chang Wook

AU - Jang, Jae Young

AU - Tak, Won Young

AU - Kim, Dong Joon

AU - Kim, In Hee

AU - Heo, Jeong

AU - Ahn, Sang Hoon

N1 - Funding Information: This investigator-initiated trial was supported by an unrestricted grant from Bristol-Myers Squibb (BMS) and clinical research grant from Pusan National University Hospital in 2018. BMS had no role in the study design and the authors retain full responsibility for the collection and interpretation of data, decision to publish, and preparation of the manuscript. Publisher Copyright: © 2020 by Korean Association for the Study of the Liver.

PY - 2020/7

Y1 - 2020/7

N2 - Background/Aims: Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV. Methods: This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded. Results: Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs.-0.37 log10 IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV-or ETVassociated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/ LdT+ADV group (P=0.106). The two groups had similar rates of adverse events. Conclusions: ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/ LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).

AB - Background/Aims: Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV. Methods: This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded. Results: Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs.-0.37 log10 IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV-or ETVassociated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/ LdT+ADV group (P=0.106). The two groups had similar rates of adverse events. Conclusions: ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/ LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).

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U2 - 10.3350/cmh.2019.0044n

DO - 10.3350/cmh.2019.0044n

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AN - SCOPUS:85087392010

SN - 2287-2728

VL - 26

SP - 352

EP - 363

JO - Clinical and molecular hepatology

JF - Clinical and molecular hepatology

IS - 3

ER -

Entecavir+tenofovir vs. Lamivudine/telbivudine+ adefovir in chronic hepatitis b patients with prior suboptimal response

Abstract

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