从2年的路线图战略的结果：在治疗慢性乙型肝炎的条件替诺

StephenW

Drugs Context. 2016 Apr 22;5:212294. doi: 10.7573/dic.212294. eCollection 2016.
Efficacy of telbivudine with conditional tenofovir intensification in patients with chronic hepatitis B: results from the 2-year roadmap strategy.Piratvisuth T1, Komolmit P2, Chan HL3, Tanwandee T4, Sukeepaisarnjaroen W5, Pessoa MG6, Fassio E7, Ono SK8, Bessone F9, Daruich J10, Zeuzem S11, Manns M12, Uddin A13, Dong Y14, Trylesinski A14.
Author information

• 1NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand;
• 2Division of Gastroenterology, Department of Medicine, Chulalongkorn University, Bangkok, Thailand;
• 3Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong S.A.R, China;
• 4Siriraj Hospital, Mahidol University, Bangkok, Thailand;
• 5Department of Medicine, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand;
• 6Division of Gastroenterology and Hepatology, University of São Paulo School of Medicine, São Paulo, Brazil;
• 7Hospital Nacional Prof. Alejandro Posadas, Buenos Aires, Argentina;
• 8Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil;
• 9School of Medicine, University of Rosario, Rosario, Argentina;
• 10Hospital de Clínicas San Martín, University of Buenos Aires, Buenos Aires, Argentina;
• 11Department of Medicine, JW Goethe University Hospital, Theodor-Stern-Kai 7, Frankfurt a.M., Germany;
• 12Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany;
• 13Novartis Pharmaceutical Corporation, East Hanover, NJ, USA;
• 14Novartis Pharma AG, Basel, Switzerland.
  

AbstractBACKGROUND: A 2-year roadmap study was conducted to evaluate the efficacy and safety of tenofovir intensification at Week 24 in patients with chronic hepatitis B (CHB) receiving telbivudine.
SCOPE: A prospective multicenter study was conducted in treatment-naive patients with hepatitis B e antigen (HBeAg)-positive CHB. All patients received telbivudine (600 mg/day) until Week 24. Thereafter, patients with detectable hepatitis B virus (HBV) DNA (≥300 copies/mL) were administered tenofovir (300 mg/day) plus telbivudine, and patients with undetectable HBV DNA continued telbivudine monotherapy until Week 104. The primary endpoint was the proportion of patients with undetectable HBV DNA (<300 copies/mL) at Weeks 52 and 104.
FINDINGS: A total of 105 patients were enrolled in the trial, of which 100 were eligible for efficacy analysis. Undetectable HBV DNA levels were observed at Week 24 in 55 patients who continued on with telbivudine monotherapy. The remaining 45 patients with detectable HBV DNA received tenofovir add-on therapy. With monotherapy, 100% (55/55) and 94.5% (52/55) of patients achieved HBV DNA <300 copies/mL at Weeks 52 and 104, respectively; the corresponding values for patients with add-on therapy were 84.4% (38/45) and 93.3% (42/45). Overall, undetectable HBV DNA (<300 copies/mL) was found in 93% (93/100) and 94% (94/100) of patients at Weeks 52 and 104, respectively. HBeAg seroconversion rate was 44.4% (44/99) at Week 104 for the overall patient population. One patient in the monotherapy group and six in the intensification group demonstrated HBsAg clearance at Week 104. HBsAg seroconversion was observed in four patients at Week 104, all belonged to the tenofovir intensification group. Eight patients sustained HBsAg loss during a posttreatment follow-up period of 16 weeks. Alanine aminotransferase (ALT) normalization was constant in the telbivudine monotherapy group, whereas a progressive improvement was observed in the tenofovir intensification group. Two patients in the monotherapy and none in the intensification group experienced viral breakthrough by Week 104. There were no reports of myopathy in either group. The mean changes in estimated glomerular filtration rate (eGFR), estimated using the Modification of Diet in Renal Disease (MDRD) formula, from baseline to Week 104 were +6.145 mL/min/1.73 m(2) (p=0.0230) and +7.954 mL/min/1.73 m(2) (p=0.0154) in the telbivudine monotherapy and tenofovir intensification groups, respectively. The incidence of serious AEs was four in the telbivudine monotherapy and two in the tenofovir intensification group. The main limitation of this study was limited sample size, which made the power of the observation low, and the absence of a comparative subgroup to assess the progression of patients with detectable HBV DNA without treatment intensification.
CONCLUSIONS: Data from this 2-year roadmap study confirmed that telbivudine with add-on tenofovir was effective and well tolerated in patients with CHB. Telbivudine was associated with an improvement in eGFR from baseline in both the groups.


KEYWORDS: chronic hepatitis B; glomerular filtration rate; hepatitis B e antigen; intensification; roadmap; telbivudine; tenofovir; virologic breakthrough

PMID:27403192DOI:10.7573/dic.212294

StephenW

药品语境。 2016年4月22日; 5：212294。 DOI：10.7573 / dic.212294。 eCollection 2016年。
从2年的路线图战略的结果：在治疗慢性乙型肝炎的条件替诺福韦替比夫定集约化的疗效。
Piratvisuth T1，Komolmit P2，陈HL3，Tanwandee T4，Sukeepaisarnjaroen W5，佩索阿MG6，Fassio E7，小野SK8，Bessone F9，Daruich J10，Zeuzem S11，M12曼斯，乌丁A13，董Y14，Trylesinski A14。
作者信息

    胃肠病学和肝病，Songklanagarind医院，医学院，大学的宋卡合艾，泰国王子学院1NKC研究所;
    消化内科，医学，朱拉隆功大学，曼谷，泰国系2区;
    香港，香港S.A.R，中国的大学中国内科及药物治疗的3Department;
    4Siriraj医院，玛希隆大学，泰国曼谷;
    医药，Srinagarind医院对孔敬大学，孔敬，泰国5Department;
    胃肠病学和肝病，医药，圣保罗，巴西圣保罗大学法学院的6Division;
    亚历杭德罗·波萨达斯7Hospital国立教授，布宜诺斯艾利斯，阿根廷;
    消化内科，医学，圣保罗，巴西圣保罗大学法学院的8Department;
    医药，罗萨里奥，阿根廷罗萨里奥大学9School;
    10Hospital德Clínicas圣马丁，布宜诺斯艾利斯，阿根廷布宜诺斯艾利斯大学;
    医药，JW歌德大学医院，西奥多·斯特恩启7，法兰克福上午，德国11Department;
    消化内科，肝病及内分泌，汉诺威医学院，德国汉诺威12Department;
    13Novartis制药公司，东汉诺威，NJ，USA;
    14Novartis制药公司，瑞士巴塞尔。

抽象
背景：

为期2年的路线图研究，以评估在第24周治疗慢性乙型肝炎（CHB）接受替比夫定的疗效和替诺福韦集约化安全。
范围：

一项前瞻性多中心研究，在治疗初治患者与乙肝e抗原（HBeAg）阳性CHB进行。所有患者都接受替比夫定（600mg /天），直至24周之后，患者可检测的乙型肝炎病毒（HBV）DNA（≥300拷贝/ ml）施用替诺福韦（300毫克/天）加替比夫定，和患者不到HBV DNA继续单药替比夫定，直到104周的主要终点是患者检测不到HBV DNA（<300拷贝/毫升）在52周和104的比例。
发现：

共有105例患者在试验，其中100例符合疗效分析患者。在55例谁替比夫定单一继续在第24周观察到检测不到的HBV DNA水平。其余45例检测到HBV DNA接受替诺福韦添加治疗。随着达到HBV DNA单药治疗的患者，100％（55/55）和94.5％（52/55）<300拷贝/毫升分别为52周和104;患者相应的值添加治疗分别为84.4％（38/45）和93.3％（42/45）。总体而言，不可检测的HBV DNA（<300拷贝/ ml）溶液在93％的患者（93/100）和94％（94/100）在周52和104，分别找到。 HBeAg血清转换率在104周为44.4％（九十九分之四十四）整体患者人群。集约化组中的单药治疗组和六中一位患者在展示104周转阴乙肝表面抗原HBsAg清除4例患者观察到在104周，所有属于替诺福韦集约化组。八患者在16周治疗后一随访期持续的HBsAg消失。丙氨酸转氨酶（ALT）正常化是替比夫定单一疗法组中恒定，而替诺福韦激化组中观察到一个逐步改善。两名患者在强化组中的单药治疗，没有经历过病毒学突破104所周目前还没有在任何一组肌病的报告。在估计肾小球滤过率的平均变化（EGFR），利用饮食的改造肾脏疾病（MDRD）公式估计，从基线到第104周分别为6.145毫升/分钟/ 1.73m米（2）（P = 0.0230）和+ 7.954毫升/分钟/ 1.73m米（2）（p值= 0.0154）分别在替比夫定单一疗法和替诺福韦集约化基，。严重不良事件的发生率是四中的替比夫定单药及两替诺福韦集约化小组。这项研究的主要限制是样本尺寸的限制，这使观察低的功率，并且没有一个比较子组，以评估患者的检测的HBV DNA的进展没有治疗激化。
结论：

从这个2年的路线图的研究数据证实附加替诺福韦是有效的，在慢性乙肝患者耐受性好替比夫定。夫定用从基线在两个组中的eGFR的改进相关联。
关键词：

慢性乙型肝炎;肾小球滤过率;乙肝e抗原;集约化;路线图;替比夫定;替诺福韦;病毒学突破

结论：
    27403192
DOI：
    10.7573 / dic.212294