| 摘要: |
| 目的 利用美国FDA不良事件报告系统（FAERS）对度普利尤单抗（dupilumab）的药物安全性进行研究，挖掘潜在的不良事件信号，为临床合理用药提供参考。方法 通过检索FAERS数据库2017年第2季度到2020年第2季度数据，将度普利尤单抗进行药名标准化后以“主要怀疑药物”作为限制条件，获得与度普利尤单抗有关的不良事件记录。通过不相称测定分析法中的报告比值法（ROR）和信息成分法（IC）挖掘潜在不良事件信号，并通过MedDRA 23.0软件对不良事件信号挖掘结果进行系统分类。结果 在16 684 618条数据记录中获得97 205条与度普利尤单抗有关的不良事件记录。根据2种不良事件信号挖掘方法所得结果，以ROR值95% CI下限>1或IC值95% CI下限>0为限制条件，共得到365个不良事件信号。通过对非不良事件的去除和同义合并，最终获得82个有较大临床意义的不良事件信号，度普利尤单抗的不良事件主要为眼部疾病、皮肤及皮下组织类疾病、感染及传染性疾病。引起严重不良事件结局的不良事件信号主要包括可能由该药物引起的眼部疾病、感染和炎症、是否存在加速皮肤T细胞淋巴瘤恶化、免疫系统的超敏反应、呼吸系统的支气管炎、骨骼系统的关节痛，以及全身性疾病及给药部位各种反应的病情恶化等。在合并用药总不良事件和严重不良事件中，合并使用的最常发生不良事件的药物前5名均为泼尼松、环孢素、曲前列环素、泼尼松龙、甲氨蝶呤。结论 度普利尤单抗不良事件除轻中度的浅角膜受损和结膜炎外，角膜变性、溃疡性角膜炎等较为严重的眼部检出信号应引起临床医师注意，并建议在指导患者用药的过程中及时联合眼科医师进行病情评估，对原有眼部问题的患者用药更需提高警惕。其他系统检出不良反应信号仍有待真实世界的药物不良反应长期监测加以证实。此外，度普利尤单抗的严重不良事件结局和对应的检出信号及最常发生不良事件的合并用药应引起重视。 |
| 关键词: 度普利尤单抗 不良事件报告系统 不良事件信号挖掘 药物警戒性 |
| DOI：10.16781/j.0258-879x.2021.07.0770 |
| 投稿时间：2021-01-21修订日期：2021-04-25 |
| 基金项目:国家自然科学基金（82073671），上海市公共卫生体系建设三年行动计划学科带头人计划（GWV-10.2-XD22），上海市卫生和计划生育委员会优秀青年医学人才培养计划（2018YQ47），上海市自然科学基金（18ZR1449500），国家科技重大专项（2017ZX09304030），国家"十三五"规划重大专项（2017ZX09304016），上海市公共卫生体系建设三年行动计划优青计划（GWV-10.2-YQ33）. |
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| Data mining and analysis for adverse event signals of dupilumab based on U. S. Food and Drug Administration Adverse Event Reporting System database |
| GUO Zhi-jian,ZHENG Yi,CHI Li-jie,GUO Xiao-jing,XU Jin-fang,YE Xiao-fei*,HE Jia* |
(Department of Medical Statistics, Faculty of Medical Services, Naval Medical University (Second Military Medical University), Shanghai 200433, China
*Corresponding authors) |
| Abstract: |
| Objective To study the safety profile of dupilumab using the U. S. Food and Drug Administration Adverse Event Reporting System (FAERS) database and to mine the potential adverse event signals, so as to provide reference for rational clinical drug use. Methods The dupilumab-related adverse event records were selected by searching the FAERS database from the second quarter of 2017 to the second quarter of 2020 and standardizing dupilumab's drug name, with the primary suspected drug as a restriction. Potential adverse event signals were mined using the disproportionality analysis, including reporting odds ratio (ROR) and information component (IC), and MedDRA 23.0 was used to systematically classify the results. Results A total of 97 205 dupilumab-related adverse event records out of 16 684 618 data records were obtained. According to the results of 2 adverse event signal mining methods, 365 adverse event signals were obtained under the restricted conditions of the lower limit of the ROR value 95% confidence interval (CI) >1 or the lower limit of the IC value 95% CI >0. Finally, 82 adverse event signals with greater clinical significance were obtained through the removal of non-adverse events and the merger of the same name, and the adverse events of dupilumab were mainly eye, skin and subcutaneous diseases, infections and infestations. The adverse event signals leading to serious adverse event outcomes mainly included eye diseases, infections and inflammations that may be caused by the drug, accelerated deterioration of cutaneous T-cell lymphoma, hypersensitivity of immune system, bronchitis of respiratory system, arthralgia and systemic diseases of skeletal system, and deterioration of various reactions at the site of administration. The top 5 drugs were prednisone, cyclosporine, treprostinil, prednisolone and methotrexate among the total adverse events and serious adverse events of drug combination. Conclusion In addition to the mild and moderate shallow corneal damage and conjunctivitis, clinicians should pay attention to the more serious eye detection signals such as corneal degeneration and ulcerative keratitis. It is also recommended to conduct a medical assessment with the ophthalmologist to instruct patients on medication. Doctors need to be more vigilant in medicine for patients with original eye problems. The adverse reaction signals detected by other systems still require long-term monitoring of adverse drug reactions of real-world medications. The outcome of serious adverse events of dupilumab and the corresponding detection signals, as well as the medications in combination with the most adverse events are worthy of attention. |
| Key words: dupilumab Adverse Event Reporting System adverse event signal mining pharmacovigilance |
