第24周时的泰诺福韦强化与替比夫定52周疗效和安全性

StephenW

PLoS One. <http://www.ncbi.nlm.nih.gov/pubmed/&gt; 2013;8(2):e54279. doi: 10.1371/journal.pone.0054279. Epub 2013 Feb 4.

52-Week Efficacy and Safety of Telbivudine with Conditional Tenofovir Intensification at Week 24 in HBeAg-Positive Chronic

Hepatitis B.

Piratvisuth T, Komolmit P, Tanwandee T, Sukeepaisarnjaroen W, Chan HL, Pessôa MG
, Fassio E, Ono SK, Bessone F, Daruich J, Zeuzem S, Cheinquer H, Pathan R, Dong Y
, Trylesinski A

Source

NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songklanagarind Hospital, Hat-Yai, Songkhla, Thailand.

Abstract

BACKGROUND AND AIMS:

The Roadmap concept is a therapeutic framework in chronic

hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated.

METHODS:

A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic

hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52.

RESULTS:

105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52.

CONCLUSIONS:

Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic
hepatitis B.

StephenW

背景与目的：

“路线图”的概念是一个框架，慢性治疗

乙型肝炎的核苷类似物单药治疗的基础上早期病毒学应答的加剧。这种方法应用替比夫定治疗的疗效和安全性的影响。

方法：

一个跨国公司，单组开放标签研究，第四阶段（ClinicalTrials.gov编号NCT00651209）核苷初治HBeAg阳性，治疗成人慢性进行

B型肝炎患者接受替比夫定（600毫克每日一次），24周后，检测不到血清HBV DNA（<300拷贝/ ml）继续单独接受替比夫定，而那些与检测到的DNA收到替比夫定加替诺福韦（300毫克每日）。在第52周的结果进行了评估。

结果：

开始替比夫定单独治疗105例患者，其中100人的疗效分析。五十五（55％），24周时HBV DNA检测不到，继续替比夫定单独治疗; 45（45％）接受替诺福韦加剧。第52周时，HBV DNA检测不到整体比例为93％（93/100），末次观察结转分析（100％单药治疗组，强化组84％），并没有发生病毒学突破。发生ALT复常，HBeAg清除77％（87％单药治疗，64％的集约化）在43％（65％的单药治疗，16％的集约化），HBeAg血清转换率在39％（62％的单药治疗，11％的集约化）。六名病人HBsAg清除。肌痛多见于单药组（19％比7％）。在第52周，发生在两个治疗组的平均肾小球滤过率没有下降。

结论：

替比夫定治疗24周时，替诺福韦集约化的路线图战略指示的位置，会出现有效且耐受性良好，用于治疗慢性乙型肝炎的

B型肝炎。