Adverse events associated with inclisiran: a real-world disproportionality analysis based on the FAERS database

Randomized clinical trials have reported some safety profiles in inclisiran, but adverse events in real-world remain insufficient. We aim to evaluate the safety of inclisiran in real-world by collecting the data from the FDA Adverse Event Reporting System database. Disproportionality analysis was performed by utilizing both Frequency method and Bayesian method to mine adverse event signals of inclisiran. A positive signal was deemed significant when adverse event met the criteria of the aforementioned methods simultaneously. We gathered a total of 2309 adverse event reports. Among these cases, adverse events were more common in females and ≥ 65 years age group. After data analysis, 51 positive signals from 11 system organ classes were identified, involving “Musculoskeletal and connective tissue disorders,” “General disorders and administration site conditions,” “Gastrointestinal disorders,” etc. At the preferred term level, the top three frequently reported adverse events were arthralgia, injection site pain and myalgia. We also found some uncommon but significantly strong adverse event signals (bladder discomfort and sinus pain) which should be taken prudently. In this study, we analyzed the real-world adverse events of inclisiran more comprehensively and reported some new adverse events, hoping that can offer more safety information for clinical medication.

随机临床试验已对英克西兰（inclisiran）的安全性特征进行了报道，但真实世界中的不良反应相关数据仍较为匮乏。本研究拟通过收集美国食品药品监督管理局不良事件报告系统（FDA Adverse Event Reporting System）数据库中的数据，对英克西兰的真实世界安全性进行评估。本研究采用频率法（Frequency method）与贝叶斯法（Bayesian method）开展不均衡分析（disproportionality analysis），以挖掘英克西兰的不良反应信号（adverse event signals）。当某一不良反应同时满足上述两种方法的判定标准时，即可认定为阳性信号。本研究共收集到2309份不良反应报告，其中不良反应在女性及65岁及以上年龄群体中更为多见。经数据分析后，从11个系统器官分类（system organ classes）中识别出51个阳性信号，涉及「肌肉骨骼与结缔组织疾病」、「全身性疾病及给药部位反应」、「胃肠道疾病」等类别。在首选术语（preferred term）层面，报告频次排名前三的不良反应为关节痛、注射部位疼痛与肌痛。本研究同时发现了若干罕见但显著性较强的不良反应信号（如膀胱不适与鼻窦痛），临床用药时需谨慎关注。本研究对英克西兰的真实世界不良反应进行了更为全面的分析，并报道了部分新型不良反应，以期为临床用药提供更为丰富的安全性参考信息。