Telbivudine versus entecavir in patients with undetectable hepatitis B virus DNA: a randomized trial

Abstract

BackgroundTelbivudine has been suggested to induce hepatitis B surface antigen (HBsAg) decline to the similar degree as pegylated interferon. We aimed to investigate whether telbivudine could further decrease HBsAg titer in patients who maintain undetectable serum hepatitis B virus (HBV) DNA after initial entecavir treatment.MethodsIn this open-label trial, patients who had serum HBsAg and HBV DNA levels ≥1,000 IU/mL and <60 IU/mL, respectively, following entecavir (0.5 mg/day) treatment for HBeAg-positive chronic hepatitis B were randomized to either switch treatment to telbivudine (600 mg/day, n = 47) or continue entecavir (n = 50) for 48 weeks.ResultsThe baseline characteristics were comparable between groups including HBsAg levels (median, 3.41 log10 IU/mL). All patients had undetectable HBV DNA and normal alanine aminotransferase level. At week 48, the mean change in serum HBsAg levels was not significantly different between the telbivudine and entecavir groups (−0.03 log10 IU/mL vs. −0.05 log10 IU/mL; P = 0.57). No patient experienced HBsAg seroclearance or HBsAg decline >0.5 log10 IU/mL. Eleven patients (23.4%) in the telbivudine group, but none in the entecavir group, experienced virologic breakthrough (P < 0.001). Seven patients (14.9%) exhibited genotypic resistance mutations (M204I +/− L180M) during the virologic breakthrough.ConclusionSequential therapy with entecavir followed by telbivudine resulted in a high rate of virologic breakthrough and drug-resistance without any beneficial effect on HBsAg decline. These results do not support the use of low genetic barrier drugs as a switch treatment strategy in patients who achieve virologic response with high genetic barrier drugs.Trial registration NCT01595685 (date of trial registration: May 8, 2012)Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-017-0572-2) contains supplementary material, which is available to authorized users.

KASL clinical practice guidelines for management of chronic hepatitis B

“…When choosing a specific NA, one should consider the efficacy and safety of the drug. Although the class effects of NAs remain unclear, each NA has a unique side effect profiles [223]. Hence, when the efficacy of one NA is expected to be similar to another NA, one should consider patient co-morbidities and the future risk of drug-related side effects when selecting an NA (Refer to “Management in Special Conditions” chapter).…”

Entecavir-based combination therapies for chronic hepatitis B

“…The four included studies, which involved 297 patients, reported the rates of HBV DNA relapse. [21,22,26,27] Because the heterogeneity was not significant among these studies (group C: P = .98, I 2 = 0%), the fixed-effect method was applied to calculate the overall effects. The rate of HBV DNA relapse was higher in the combination therapy group than in ETV monotherapy group (OR = 19.57, 95% CI: 4.60–83.37, P < .0001; Figure S3).…”

Are Published Health Economic Models for Chronic Hepatitis B Appropriately Capturing the Benefits of HBsAg Loss? A Systematic Literature Review

“…Meanwhile, as stated previously, it was not clear which values Jones et al [45] used in the accompanying EE. In published RCTs, HBsAg loss recorded at 48 weeks for nucleosides rarely reaches 4% or higher [12][13][14][15][16][17]; therefore, numerous studies seem to state loss rates that are particularly high in their models.…”

“…This may lead to an under-reporting of FC in clinical trials, observational studies and health economic (HE) models. Most published randomised controlled trials (RCTs) record annual HBsAg loss rates that rarely reach > 4% for nucleoside therapies [12][13][14][15][16][17], and usually around 4-10% for PEG IFN [18][19][20][21] (though 20% [22] and 21% [23] have been seen in some cases, with low sample sizes appearing to have an influence, i.e., two and three patients experiencing HBsAg loss, respectively).…”