Dataset Information

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 ETV-associated 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. CONCLUSION: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).

SUBMITTER: Woo HY

PROVIDER: S-EPMC7364362 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Woo Hyun Young HY Park Jun Yong JY Bae Si Hyun SH Kim Chang Wook CW Jang Jae Young JY Tak Won Young WY Kim Dong Joon DJ Kim In Hee IH Heo Jeong J Ahn Sang Hoon SH

Clinical and molecular hepatology 20200528 3

<h4>Background/aims</h4>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.<h4>Methods</h4>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-resi ...[more]

PMID: 32460460

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Project description:To examine the efficacy of telbivudine (LdT) + adefovir (ADV) vs continuation of lamivudine (LAM) + ADV in patients with LAM-resistant chronic hepatitis B (CHB) who show a suboptimal response to LAM + ADV.This was a randomized, active-control, open-label, single-center, parallel trial. All eligible patients were enrolled in this study in Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea, between March 2010 and March 2011. Hepatitis Be antigen (HBeAg)-positive CHB patients whose serum hepatitis B virus (HBV) DNA remained detectable despite at least 6 mo of LAM + ADV therapy were included. Enrolled patients were randomized to either switching to LdT (600 mg/d orally) plus ADV (10 mg/d orally) (LdT + ADV group) or to continuation with LAM (100 mg/d orally) plus ADV (10 mg/d orally) (LAM + ADV group), and were followed for 48 wk. One hundred and six patients completed the 48-wk treatment period. Serum HBV DNA, HBeAg status, liver biochemistry and safety were monitored at baseline and week 12, 24, 36 and 48.The duration of prior LAM + ADV treatment was 18.3 (LdT + ADV) and 14.9 mo (LAM + ADV), respectively (P = 0.131). No difference was seen in baseline serum HBV DNA between the two groups [3.66 (LdT + ADV) vs 3.76 (LAM + ADV) log10 IU/mL, P = 0.729]. At week 48, although there was no significant difference in the mean reduction of serum HBV DNA from baseline between LdT + ADV group and LAM + ADV group (-0.81 vs -0.47 log10 IU/mL, P = 0.167), more patients in the LdT + ADV group had undetectable HBV DNA levels compared to those in the LAM + ADV group (30.2% vs 11.5%, P = 0.019). Three patients with LdT + ADV treatment and 2 patients with LAM + ADV treatment achieved HBeAg loss. The patients in both groups tolerated the treatment well without serious adverse events. The proportion of patients with estimated glomerular filtration rate ? 90 mL/min per 1.73 m(2) in the LdT + ADV group increased from 49.1% (26/53) at baseline to 58.5% (31/53) at week 48, while that in the LAM + ADV group decreased from 37.7% (20/53) at baseline to 30.2% (16/53) at week 48.The switch to LdT + ADV in suboptimal responders to LAM + ADV showed a significantly higher rate of virologic response at week 48. These results suggest that LdT + ADV could be a therapeutic option for patients who are unable to use enofovir disoproxil fumarate for any reason.

Project description:AIM:To make efficacy and safety comparison of telbivudine-raodmap and tenofovir-roadmap in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. METHODS:This was the first prospective, randomised, two-arm, open-label, non-inferiority study in HBeAg-negative CHB patients that compared telbivudine and tenofovir administered as per roadmap concept. Patients were treated up to 24 wk and, depending on virologic response, continued the same therapy or received add-on therapy up to 104 wk. Eligible patients received an additional 52 wk of treatment in the extension period (i.e., up to 156 wk). Patients who developed virologic breakthrough (VB) while on monotherapy also received add-on therapy. The primary efficacy endpoint was the rate of patients achieving hepatitis B virus (HBV) DNA < 300 copies/mL at week 52. Secondary efficacy endpoints included the rates of HBV DNA < 300 and < 169 copies/mL, HBV DNA change from baseline, alanine aminotransferase normalisation, hepatitis B surface antigen (HBsAg) loss, HBsAg seroconversion, VB, and emergence of resistance at various timepoints throughout the study. Safety and estimated glomerular filtration rate (eGFR) were also analysed. RESULTS:A total of 241 patients were randomised. Non-inferiority of telbivudine arm to tenofovir arm was demonstrated at week 52 (± 7 d window), with over 91% of patients in each treatment arm achieving HBV DNA level < 300 copies/mL. Both arms were similar in terms of key secondary efficacy variables at weeks 104 and 156. The percentage of patients achieving HBV DNA < 300 copies/mL remained high and was similar in the telbivudine and tenofovir arms at both weeks 104 and 156. Over 82% of patients in both arms achieved alanine aminotransferase normalisation at week 52, and this percentage remained high at weeks 104 and 156. Telbivudine treatment progressively reduced serum HBsAg levels from baseline while no change was reported in quantitative HBsAg during therapy with tenofovir. Both treaments showed acceptable safety profiles. The telbivudine arm showed eGFR improvement unlike the tenofovir arm. CONCLUSION:Efficacy was shown for both telbivudine-roadmap and tenofovir-roadmap regimens in HBeAg-negative CHB patients over 156 wk. Telbivudine arm was associated with renal improvement.

Dataset Information

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

Publications

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

Similar Datasets

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