目的:基于美国食品药品监督管理局不良事件报告系统(FAERS)的公共上报数据,挖掘分析及研究靶向IL-6药物在真实世界发生的药物不良事件,为临床合理用药提供参考。方法:采用报告比值比法和贝叶斯置信度递进神经网络法对FAERS数据库中2010年第1季度至2022年第4季度收到的4种靶向IL-6药物托珠单抗、司妥昔单抗、萨瑞鲁单抗、萨特利珠单抗为首要怀疑药物的药物不良事件(ADE)数据进行挖掘,利用国际医学用语词典的系统器官分类(SOC)和首选术语(PT)对ADE进行统计分析,以上两种方法计算均产生信号即认定为风险信号。结果:2010年第1季度至2022年第4季度FAERS共收到以所有靶向IL-6药物为首要怀疑药物的ADE共138 239例,风险ADE信号846个,报告对象以女性居多,年龄集中于45~65岁,上报事件来源以美国及欧洲国家为主,报告年份在药物上市后呈逐年递增的趋势。托珠单抗的ADE信号有850个(123 729例),涉及27个SOC,说明书中未提及的SOC有11个;萨瑞鲁单抗的ADE信号有190个(14 917例),涉及17个SOC,说明书中未提及的SOC有10个;萨特利珠单抗的ADE信号有30个(218例),涉及14个SOC,说明书中未提及的SOC有6个;司妥昔单抗的ADE信号有15个(107例),涉及8个SOC,说明书中未提及的SOC有1个。结论:基于FAERS数据库对靶向IL-6药物可疑不良反应信号的挖掘,发现部分说明书中尚未提及的不良事件信号,可以为未来靶向IL-6药物临床安全用药提供参考。 |
Objective: To analyze the adverse drug events(ADE) of targeted IL-6 drugs in the real world using the FDA adverse event reporting system(FAERS) database, and to provide reference for rational clinical medication. Methods: The reporting odds ratio method and Bayesian confidence propagation neural network method were used to mine the ADE data of four IL-6 targeted drugs received in the FAERS database from the first quarter of 2010 to the fourth quarter of 2022, with Tocilizumab, Siltuximab, Sarilumab and Satralizumab as the primary suspected drugs. Statistical analysis of ADE was conducted using the system organ class(SOC) and preferred term(PT) of the Medical Dictionary for Regular Activities. Results: FAERS received 138 239 cases of ADE with all targeted IL-6 drugs as the primary suspect drugs, with 846 risk ADE signals. Most reporting objects were women, with the age of 45 to 65 years old. The main sources of reported events were the United States and European countries. The reporting year showed an increasing trend year by year after the drug was launched. Mining for four drugs found that there were 850 ADE signals(123 729 cases) of Tocilizumab, involving 27 SOCs, and 11 SOCs not mentioned in the instructions. Sarilumab had 190 ADE signals(14 917 cases), involving 17 SOCs, and 10 SOCs not mentioned in the specification.There were 30 ADE signals(218 cases) of Satralizumab, involving 14 SOCs, and 6 SOCs not mentioned in the specification.There were 15 ADE signals(107 cases) of Siltuximab, involving 8 SOCs, and there was 1 SOC not mentioned in the specification. Conclusion: Some adverse event signals that have not been mentioned in the instructions are found in this study, which can provide reference for the safe clinical use of targeted IL-6 drugs in the future. |
[1] 姜少杰,梁仕睿,张雪芹,等.IL-6/IL-6受体轴及其靶向抑制剂研究进展[J].细胞与分子免疫学杂志,2019,35(6):569-574.
[2] TROVATO M,SCIACCHITANO S,FACCIOLA A,et al.Interleukin-6 signalling as a valuable cornerstone for molecular medicine(Review)[J].Int J Mol Med,2021,47(6):1-9.
[3] KAMATH A,ACHARYA S D,RAO R R,et al.Assessment of pancreatitis associated with tocilizumab use using the United States Food and Drug Administration Adverse Event Reporting System database[J].Sci Rep,2021,11(1):18818.
[4] 左玮,刘容吉,许秀丽,等.托珠单抗不良反应研究进展[J].临床药物治疗杂志,2020,18(3):16-20.
[5] MIN G J,JENO Y W,PARK S S,et al.The clinical,laboratory,and radiologic improvement due to siltuximab treatment in idiopathic multicentric Castleman's disease[J].Korean J Intern Med,2021,36(2):424-432.
[6] TANAKA Y,WADA K,TAKAHASHI Y,et al.Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate:results of a randomized,placebo-controlled phase Ⅲ trial in Japan[J].Arthritis Res Ther,2019,21(1):1-14.
[7] TRABOULSEE A,GREENBERG B M,BENNETT J L,et al.Safety and efficacy of satralizumab monotherapy in neuromyelitisoptica spectrum disorder:a randomised,double-blind,multicentre,placebo-controlled phase 3 trial[J].Lancet Neurol,2020,19(5):402-412.
[8] 王欢,李执,徐德宇,等.新型冠状病毒肺炎危重症患者临 床特征研究[J].东南大学学报(医学版),2020,39(4):475-479.
[9] LI Y S,REN H C,CAO J H.Roles of Interleukin-6-mediated immunometabolic reprogramming in COVID-19 and other viral infection-associated diseases[J].Int Immunopharmacol,2022,110:109005.
[10] 舒亚民,丁玉峰,张琪琳,等.基于FAERS数据库的奥曲肽不良反应信号挖掘与分析[J].药物评价研究,2021,44(12):2705-2710.
[11] 遵平,吴利利.基于BCPNN法对依洛尤单抗不良反应信号的挖掘与分析[J].遵义医科大学学报,2022,45(5):638-643.
[12] KHAN F A,STEWART I,FABBRI L,et al.Systematic review and meta-analysis of anakinra,sarilumab,siltuximab and tocilizumab for COVID-19[J].Thorax,2021,76(9):907-919.
[13] MAJIDPOOR J,MORTEZAEE K.Interleukin-6 in SARS-CoV-2 induced disease:interactions and therapeutic applications[J].Biomed Pharmacother,2022,145:112419.
[14] VILLAESCUSA L,ZARAGOZA F,GAYO-ABELEIRA I,et al.A new approach to the management of COVID-19.Antagonists of IL-6:Siltuximab[J].Adv Ther,2022,39(3):1126-1148. |
