Medical School of Hannover, Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
Expert Opin Drug Saf. 2012 May;11(3):361-8. doi: 10.1517/14740338.2012.653340. Epub 2012 Jan 11.
To review long-term safety data from the rollover study ETV-901, focusing on adverse events (AEs) with a potential nucleos(t)ide association.
The open-label study ETV-901 (AI463901) assessed the safety of entecavir in chronic hepatitis B patients who received entecavir, lamivudine or adefovir monotherapy in previous entecavir Phase II/III studies. Long-term cumulative safety results are based on reported AEs, regardless of causal relationship.
Median exposure to entecavir in study ETV-901 was 184 weeks. Commonly reported AEs (≥ 10%) were upper respiratory tract infection, headache and nasopharyngitis. Most AEs were mild to moderate; 203 (19%) patients reported grade 3 - 4 AEs, with 45 (4%) considered related to entecavir. There were 14 (1%) discontinuations due to AEs. On-treatment alanine aminotransferase (ALT) flares were reported in 32 (3%) patients and were associated with a reduction in hepatitis B virus DNA of more than 2 log(10) copies/ml in 25/32 patients. AEs potentially associated with nucleos(t)ide analogs were infrequent, the most common being myalgia (n = 54; 5%) and neuropathy-related AEs (hypoparesthesia and hyperparesthesia, polyneuropathy; n = 42; 4%).
Long-term administration of entecavir was associated with low rates of serious AEs, discontinuations due to AEs and ALT flares. AEs potentially associated with nucleos(t)ide use occurred at low rates.
回顾 ETV-901 翻滚研究的长期安全性数据，重点关注与核苷（酸）相关的潜在不良事件（AE）。
开放性研究 ETV-901（AI463901）评估了恩替卡韦在先前接受过恩替卡韦、拉米夫定或阿德福韦单药治疗的慢性乙型肝炎患者中的安全性，这些患者来自恩替卡韦 II/III 期研究。长期累积安全性结果基于报告的 AE，无论因果关系如何。
研究 ETV-901 中恩替卡韦的中位暴露时间为 184 周。常见报告的 AE（≥10%）为上呼吸道感染、头痛和鼻咽炎。大多数 AE 为轻度至中度；203 名（19%）患者报告了 3-4 级 AE，其中 45 名（4%）认为与恩替卡韦有关。有 14 名（1%）患者因 AE 停药。14 名（1%）患者因 AE 停药。治疗期间丙氨酸氨基转移酶（ALT）升高的报告发生率为 32%（3%），25/32 例患者的乙型肝炎病毒 DNA 下降超过 2 个对数（10）拷贝/ml。与核苷（酸）类似物相关的 AE 较为罕见，最常见的是肌痛（n=54；5%）和神经病变相关的 AE（感觉减退和感觉过度、多发性神经病；n=42；4%）。
长期使用恩替卡韦与严重 AE 发生率低、因 AE 停药和 ALT 升高发生率低有关。与核苷（酸）使用相关的 AE 发生率较低。
