Adverse event profile of CGRP monoclonal antibodies: findings from the FDA adverse event reporting database

Four CGRP Monoclonal Antibodies (mAbs) have been approved for migraine prophylaxis by the Food and Drug Administration (FDA) since 2018. However, there are concerns about the safety of these four drugs for real-world use. To compare the adverse event profiles of four CGRP-mAbs with FAERS data. The study was based on records from the FAERS database. Only reports containing one of the active ingredients with CGRP-mAbs were included in this study. Disproportionality analyses including but not limited to reporting odds ratio (ROR) and information components (IC) were conducted to identify drug-AE associations. In total, 58110 reports were identified for CGRP-mAbs. 80 overlapping signals were disproportionately reported. They affected a range of organs and systems, including the gastrointestinal and cardiovascular systems, skin, and hair. Additionally, the rare cardiovascular adverse events were significantly different among the four CGRP-mAbs. We identified numerous shared underlying signals (overlapping signals) for CGRP-mAbs as suspected drugs in multiple systems and organs. The unlabeled common signals may indicate potential safety issues. In addition, the underlying safety signals varied among the four CGRP-mAbs, particularly in the cardiovascular system, and further studies are needed to confirm these associations and the potential clinical implications.

自2018年以来，美国食品药品监督管理局（FDA）已批准四款降钙素基因相关肽单克隆抗体（CGRP Monoclonal Antibodies, mAbs）用于偏头痛的预防性治疗。然而，这四款药物在真实世界应用中的安全性仍存在诸多顾虑。本研究旨在基于FDA不良事件报告系统（FAERS）数据库的数据，对比四款CGRP单克隆抗体的不良事件特征谱；研究仅纳入提及CGRP单克隆抗体任一活性成分的报告，并采用不成比例分析方法，涵盖但不限于报告比值比（ROR）与信息成分（IC），以识别药物-不良事件（Adverse Event, AE）关联。最终共检索到58110条CGRP单克隆抗体相关报告，其中80个重叠信号（overlapping signals）被判定为存在报告失衡的信号，这些信号累及多系统多器官，包括胃肠道与心血管系统、皮肤及毛发系统；此外，四款CGRP单克隆抗体的罕见心血管不良事件发生率存在显著差异。本研究识别出多款CGRP单克隆抗体作为可疑药物时，在多系统多器官存在大量共有的潜在信号（重叠信号），这些未在药品说明书中标注的共同信号或提示潜在的安全性风险；同时，四款CGRP单克隆抗体的潜在安全性信号存在差异，尤以心血管系统为甚，需开展进一步研究以验证这些关联及其潜在的临床意义。