基于FAERS对白介素17A抑制剂相关炎症性肠病不良事件数据挖掘与分析

Data Mining and Analysis of Adverse Events of Interleukin-17A Inhibitors in the Aspects of Inflammatory Bowel Disease Based on FAERS

关键词:  司库奇尤单抗  依奇珠单抗  布罗利尤单抗  银屑病  炎症性肠病  FDA不良事件报告系统

Key words:  secukinumab  ixekizumab  brodalumab  psoriasis  inflammatory bowel disease  FDA adverse event reporting system

摘要:

目的 对白介素17A抑制剂相关炎症性肠病(inflammatory bowel disease，IBD)不良事件的情况进行数据挖掘与分析，为临床安全应用提供参考。方法 收集2004年第一季度—2021年第四季度美国FDA不良事件报告系统(FDA Adverse Event Reporting System，FAERS)以司库奇尤单抗、依奇珠单抗和布罗利尤单抗为首要怀疑药物，不良事件为IBD、克罗恩病(Crohn’s disease，CD)和溃疡性结肠炎(ulcerative colitis，UC)的报告，采用报告比值比法(reported odds ratio，ROR)和比例报告比值比法(proportional reported odds ratio，PRR)对信号进行检测分析。结果 共收集到IBD相关报告2 578份，其中司库奇尤单抗2 286份(88%)，依奇珠单抗289份(11%)，布罗利尤单抗3份(1%)，涉及银屑病患者810例。3种药物严重不良事件的发生率分别为32.47%，33.11%和33.33%，均以“住院/住院时间延长”为主。司库奇尤单抗[ROR=4.123，95%CI(3.564，4.769)，PRR=4.116，95%CI(3.559，4.759)]和依奇珠单抗[ROR=5.503，95%CI(4.127，7.336)，PRR=5.448，95%CI(4.12，7.31)]均以未区分CD或UC的IBD信号最强，布罗利尤单抗没有检测到相关信号。结论 司库奇尤单抗和依奇珠单抗均有导致IBD的风险，严重不良事件发生率较高，可能影响患者生存质量。使用时应注意评估，尤其对IBD高风险人群使用该类药物的安全性应引起关注。

Abstract:

OBJECTIVE To conduct data mining and analysis on the adverse events of interleukin-17A inhibitors in the aspects of inflammatory bowel disease(IBD) in order to provide reference for clinical safety application. METHODS Adverse events of IBD, Crohn’s disease(CD) and ulcerative colitis(UC) were collected from FDA Adverse Event Reporting System(FAERS) during the first quarter of 2004 to the fourth quarter of 2021 with secukinumab, ixekizumab and brodalumab as the primary suspect drugs. The reported odds ratio method(ROR) and proportional reported odds ratio method(PRR) were used to detect and analysis the signal. RESULTS A total of 2 578 IBD-related reports were collected, including 2 286(88%) for secukinumab, 289(11%) for ixekizumab and 3(1%) for brodalumab, involving 810 patients with psoriasis. The incidence of serious adverse events of the three drugs were 32.47%, 33.11% and 33.33%, which were mainly “Hospitalization/Initial or Prolonged”. The IBD signal that didn’t distinguish CD or UC was the strongest signal with secukinumab[ROR=4.123, 95%CI(3.564, 4.769), PRR=4.116, 95%CI(3.559, 4.759)] and ixekizumab[ROR=5.503, 95%CI(4.127, 7.336), PRR=5.448, 95%CI(4.12, 7.31)], no relevant signal was detected with brodalumab. CONCLUSION Both secukinumab and ixekizumab have the risk of causing IBD, and the incidence of serious adverse events is high, which may affect the quality of life. Attention should be paid during the application of these drugs, especially for the patients with high-risk of IBD.