Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure: Results of a randomised trial

Young Suk Lim, Kwan Soo Byun, Byung Chul Yoo, So Young Kwon, Yoon Jun Kim, Jihyun An, Han Chu Lee, Yung Sang Lee

Research output: Contribution to journalArticle

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Abstract

Objective: Little clinical data are available regarding the optimal treatment of patients who harbour entecavir (ETV)-resistant HBV. Design: In this multicentre randomised trial, patients who had HBV with ETV resistance-associated mutations and serum HBV DNA concentrations >60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=45) or TDF and ETV (1 mg/day) combination therapy (n=45) for 48 weeks. Results: Baseline characteristics were comparable between groups, including HBV DNA levels (median, 4.02 log10 IU/mL) and hepatitis B e antigen-positivity (89%). All patients had at least one ETV-resistance mutation: rtT184A/C/F/G/I/L/S (n=49), rtS202G (n=43) and rtM250L/V (n=7), in addition to rtM204V/I (n=90). All except one patient in the TDF group completed 48 weeks of treatment. At week 48, the proportion of patients with HBV DNA <15 IU/mL, the primary efficacy endpoint, was not significantly different between the TDF and TDF+ETV groups (71% vs 73%; p>0.99). The mean change in HBV DNA levels from baseline was not significantly different between groups (-3.66 vs-3.74 log10 IU/mL; p=0.81). Virological breakthrough occurred in one patient on TDF, which was attributed to poor drug adherence. At week 48, six and three patients in the TDF and TDF+ETV groups, respectively, retained their baseline resistance mutations (p>0.99). None developed additional resistance mutations. Safety profiles were comparable in the two groups. Conclusions: TDF monotherapy for 48 weeks provided a virological response comparable to that of TDF and ETV combination therapy in patients infected with ETV-resistant HBV. Trial registration number ClinicalTrials.gov ID NCT01639092.

Original languageEnglish
Pages (from-to)852-860
Number of pages9
JournalGut
Volume65
Issue number5
DOIs
Publication statusPublished - 2016 May 1

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Tenofovir
Chronic Hepatitis B
Pharmaceutical Preparations
Mutation
DNA
Therapeutics
Hepatitis B e Antigens
entecavir

ASJC Scopus subject areas

  • Gastroenterology

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Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure : Results of a randomised trial. / Lim, Young Suk; Byun, Kwan Soo; Yoo, Byung Chul; Kwon, So Young; Kim, Yoon Jun; An, Jihyun; Lee, Han Chu; Lee, Yung Sang.

In: Gut, Vol. 65, No. 5, 01.05.2016, p. 852-860.

Research output: Contribution to journalArticle

Lim, Young Suk ; Byun, Kwan Soo ; Yoo, Byung Chul ; Kwon, So Young ; Kim, Yoon Jun ; An, Jihyun ; Lee, Han Chu ; Lee, Yung Sang. / Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure : Results of a randomised trial. In: Gut. 2016 ; Vol. 65, No. 5. pp. 852-860.
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abstract = "Objective: Little clinical data are available regarding the optimal treatment of patients who harbour entecavir (ETV)-resistant HBV. Design: In this multicentre randomised trial, patients who had HBV with ETV resistance-associated mutations and serum HBV DNA concentrations >60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=45) or TDF and ETV (1 mg/day) combination therapy (n=45) for 48 weeks. Results: Baseline characteristics were comparable between groups, including HBV DNA levels (median, 4.02 log10 IU/mL) and hepatitis B e antigen-positivity (89{\%}). All patients had at least one ETV-resistance mutation: rtT184A/C/F/G/I/L/S (n=49), rtS202G (n=43) and rtM250L/V (n=7), in addition to rtM204V/I (n=90). All except one patient in the TDF group completed 48 weeks of treatment. At week 48, the proportion of patients with HBV DNA <15 IU/mL, the primary efficacy endpoint, was not significantly different between the TDF and TDF+ETV groups (71{\%} vs 73{\%}; p>0.99). The mean change in HBV DNA levels from baseline was not significantly different between groups (-3.66 vs-3.74 log10 IU/mL; p=0.81). Virological breakthrough occurred in one patient on TDF, which was attributed to poor drug adherence. At week 48, six and three patients in the TDF and TDF+ETV groups, respectively, retained their baseline resistance mutations (p>0.99). None developed additional resistance mutations. Safety profiles were comparable in the two groups. Conclusions: TDF monotherapy for 48 weeks provided a virological response comparable to that of TDF and ETV combination therapy in patients infected with ETV-resistant HBV. Trial registration number ClinicalTrials.gov ID NCT01639092.",
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AU - Lim, Young Suk

AU - Byun, Kwan Soo

AU - Yoo, Byung Chul

AU - Kwon, So Young

AU - Kim, Yoon Jun

AU - An, Jihyun

AU - Lee, Han Chu

AU - Lee, Yung Sang

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N2 - Objective: Little clinical data are available regarding the optimal treatment of patients who harbour entecavir (ETV)-resistant HBV. Design: In this multicentre randomised trial, patients who had HBV with ETV resistance-associated mutations and serum HBV DNA concentrations >60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=45) or TDF and ETV (1 mg/day) combination therapy (n=45) for 48 weeks. Results: Baseline characteristics were comparable between groups, including HBV DNA levels (median, 4.02 log10 IU/mL) and hepatitis B e antigen-positivity (89%). All patients had at least one ETV-resistance mutation: rtT184A/C/F/G/I/L/S (n=49), rtS202G (n=43) and rtM250L/V (n=7), in addition to rtM204V/I (n=90). All except one patient in the TDF group completed 48 weeks of treatment. At week 48, the proportion of patients with HBV DNA <15 IU/mL, the primary efficacy endpoint, was not significantly different between the TDF and TDF+ETV groups (71% vs 73%; p>0.99). The mean change in HBV DNA levels from baseline was not significantly different between groups (-3.66 vs-3.74 log10 IU/mL; p=0.81). Virological breakthrough occurred in one patient on TDF, which was attributed to poor drug adherence. At week 48, six and three patients in the TDF and TDF+ETV groups, respectively, retained their baseline resistance mutations (p>0.99). None developed additional resistance mutations. Safety profiles were comparable in the two groups. Conclusions: TDF monotherapy for 48 weeks provided a virological response comparable to that of TDF and ETV combination therapy in patients infected with ETV-resistant HBV. Trial registration number ClinicalTrials.gov ID NCT01639092.

AB - Objective: Little clinical data are available regarding the optimal treatment of patients who harbour entecavir (ETV)-resistant HBV. Design: In this multicentre randomised trial, patients who had HBV with ETV resistance-associated mutations and serum HBV DNA concentrations >60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=45) or TDF and ETV (1 mg/day) combination therapy (n=45) for 48 weeks. Results: Baseline characteristics were comparable between groups, including HBV DNA levels (median, 4.02 log10 IU/mL) and hepatitis B e antigen-positivity (89%). All patients had at least one ETV-resistance mutation: rtT184A/C/F/G/I/L/S (n=49), rtS202G (n=43) and rtM250L/V (n=7), in addition to rtM204V/I (n=90). All except one patient in the TDF group completed 48 weeks of treatment. At week 48, the proportion of patients with HBV DNA <15 IU/mL, the primary efficacy endpoint, was not significantly different between the TDF and TDF+ETV groups (71% vs 73%; p>0.99). The mean change in HBV DNA levels from baseline was not significantly different between groups (-3.66 vs-3.74 log10 IU/mL; p=0.81). Virological breakthrough occurred in one patient on TDF, which was attributed to poor drug adherence. At week 48, six and three patients in the TDF and TDF+ETV groups, respectively, retained their baseline resistance mutations (p>0.99). None developed additional resistance mutations. Safety profiles were comparable in the two groups. Conclusions: TDF monotherapy for 48 weeks provided a virological response comparable to that of TDF and ETV combination therapy in patients infected with ETV-resistant HBV. Trial registration number ClinicalTrials.gov ID NCT01639092.

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