Zhu Chengyu, Cui Zhiwei, Liu Tingting, Lou Siyu, Zhou Linmei, Chen Junyou, Zhao Ruizhen, Wang Li, Ou Yingyong, Zou Fan
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Front Pharmacol. 2025 Mar 12;16:1531514. doi: 10.3389/fphar.2025.1531514. eCollection 2025.
Elexacaftor/Tezacaftor/Ivacaftor (ETI) has demonstrated significant efficacy in enhancing clinical outcomes for patients with cystic fibrosis (CF). Despite this, comprehensive post-marketing assessments of its adverse drug events (ADEs) remain insufficient. This study aims to analyze the ADEs associated with ETI using the U.S. FDA Adverse Event Reporting System (FAERS).
We conducted a pharmacovigilance analysis utilizing FAERS data from Q4 2019 to Q3 2024. Reports of ADEs related to ETI were extracted, and disproportionality analyses-including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS)-were employed to evaluate signal strength. Additionally, a time-to-onset (TTO) analysis was performed.
A total of 28,366 ETI-related ADEs were identified, spanning 27 organ systems. We identified 322 positive signals, with signals consistent with the drug label including headache (702 cases, ROR 2.75), infective pulmonary exacerbation of CF (691 cases, ROR 384.24), rash (538 cases, ROR 2.72), and cough (507 cases, ROR 3.79). Unexpected signals were also noted, such as anxiety (494 cases, ROR 4.16), depression (364 cases, ROR 4.59), insomnia (281 cases ROR 2.83), nephrolithiasis (79 cases, ROR 3.63) and perinatal depression (4 cases, ROR 13.59). The TTO analysis indicated that the median onset of ADEs was 70 days, with 37.08% occurring within the first month. Subgroup analyses revealed that females exhibited a higher reporting rank for mental disorder and constipation, whereas in males, they were insomnia, abdominal pain, and nasopharyngitis.
This study highlights both recognized and unexpected ADEs associated with ETI, underscoring the necessity for ongoing monitoring, particularly concerning psychiatric conditions. The subgroup analysis suggests a need for personalized treatment strategies to optimize patient care.
依列卡福妥/替扎卡福妥/依伐卡托（ETI）已显示出在改善囊性纤维化（CF）患者临床结局方面具有显著疗效。尽管如此，对其药品不良反应（ADEs）进行全面的上市后评估仍然不足。本研究旨在利用美国食品药品监督管理局不良事件报告系统（FAERS）分析与ETI相关的ADEs。
我们利用2019年第四季度至2024年第三季度的FAERS数据进行了药物警戒分析。提取与ETI相关的ADEs报告，并采用不成比例分析，包括报告比值比（ROR）、比例报告比（PRR）、贝叶斯置信传播神经网络（BCPNN）和多项目伽马泊松收缩器（MGPS）来评估信号强度。此外，还进行了发病时间（TTO）分析。
共确定了28366例与ETI相关的ADEs，涉及27个器官系统。我们确定了322个阳性信号，与药品标签一致的信号包括头痛（702例，ROR 2.75）、CF感染性肺部加重（691例，ROR 384.24）、皮疹（538例，ROR 2.72）和咳嗽（507例，ROR 3.79）。还注意到了意外信号，如焦虑（494例，ROR 4.16）、抑郁（364例，ROR 4.59）、失眠（281例，ROR 2.83）、肾结石（79例，ROR 3.63）和围产期抑郁（4例，ROR 13.59）。TTO分析表明，ADEs的中位发病时间为70天，37.08%发生在第一个月内。亚组分析显示，女性在精神障碍和便秘方面的报告排名较高，而男性则是失眠、腹痛和鼻咽炎。
本研究突出了与ETI相关的已确认和意外的ADEs，强调了持续监测的必要性，特别是关于精神疾病方面。亚组分析表明需要个性化的治疗策略以优化患者护理。
