Cardiovascular and pulmonary adverse events in patients treated with BCR-ABL inhibitors: Data from the FDA Adverse Event Reporting System
Cardiovascular and pulmonary adverse events in patients treated with BCR-ABL inhibitors: Data from the FDA Adverse Event Reporting System
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DOI：
10.1002/ajh.23938
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发表时间：
2015-04-01
影响因子：
12.8
通讯作者：
Wallis, Nicola T.
中科院分区：
文献类型：
--
作者：
Cortes, Jorge;Mauro, Michael;Wallis, Nicola T.
在接受BCR-ABL抑制剂治疗的慢性粒细胞白血病患者中报告了罕见但严重的心血管和肺部不良事件（AE）。由于严格的研究入选标准、相对较小的样本量和有限的随访时间，临床试验数据可能无法反映BCR-ABL抑制剂的完整AE特征。为了确定FDA AE报告系统（FAERS）监测数据库在识别上市后患者人群中可能与BCR-ABL抑制剂伊马替尼、达沙替尼和尼洛替尼相关的AE方面的效用，我们对相关系统器官分类中AE的FAERS报告进行了多项伽玛泊松收缩率分析。检测到与这些药物的已知安全性特征一致的信号以及描述不充分的AE的信号。骨髓坏死、结膜出血和腹膜液体潴留事件与伊马替尼唯一相关。达沙替尼组最常达到阈值的AE包括与出血和液体潴留相关的术语，包括胸腔积液和心包积液。仅尼洛替尼达到阈值的大多数术语与外周和心血管事件相关。尽管这种类型的分析无法确定AE发生率或确立因果关系，但这些结果阐明了多项临床试验中接受BCR-ABL抑制剂治疗的患者以及社区环境中所有获批和未获批适应症中报告的AE，表明需要进一步研究药物-AE相关性。这些发现强调了在选择BCR-ABL抑制剂时需要考虑患者的合并症。Am. J. Hematol. 90：E66-E72，2015. (c)2015 Wiley Periodicals，Inc.
Rare but serious cardiovascular and pulmonary adverse events (AEs) have been reported in patients with chronic myeloid leukemia treated with BCR-ABL inhibitors. Clinical trial data may not reflect the full AE profile of BCR-ABL inhibitors because of stringent study entry criteria, relatively small sample size, and limited duration of follow-up. To determine the utility of the FDA AE Reporting System (FAERS) surveillance database for identifying AEs possibly associated with the BCR-ABL inhibitors imatinib, dasatinib, and nilotinib in the postmarketing patient population, we conducted Multi-Item Gamma Poisson Shrinker disproportionality analyses of FAERS reports on AEs in relevant system organ classes. Signals consistent with the known safety profiles of these agents as well as signals for less well-described AEs were detected. Bone marrow necrosis, conjunctival hemorrhage, and peritoneal fluid retention events were uniquely associated with imatinib. AEs that most commonly reached the threshold for dasatinib consisted of terms relating to hemorrhage and fluid retention, including pleural effusion and pericardial effusion. Most terms that reached the threshold solely with nilotinib were related to peripheral and cardiac vascular events. Although this type of analysis cannot determine AE incidence or establish causality, these findings elucidate the AEs reported in patients treated with BCR-ABL inhibitors across multiple clinical trials and in the community setting for all approved and nonapproved indications, suggesting drug-AE associations warrant further investigation. These findings emphasize the need to consider patient comorbidities when selecting amongst BCR-ABL inhibitors. Am. J. Hematol. 90:E66-E72, 2015. (c) 2015 Wiley Periodicals, Inc.