质子泵抑制剂导致的急性泛发性发疹性脓疱病:基于真实世界的药物警戒研究

Acute Generalized Exanthematous Pustulosis Caused by Proton Pump Inhibitors:A Real⁃World Pharmacovigilance Study

目的探讨不同质子泵抑制剂(proton pump inhibitors,PPIs)与急性泛发性发疹性脓疱病(acute generalized exanthematous pustulosis,AGEP)的关联性及特点。方法检索2004年1月至2020年6月美国食品药品监督管理局不良事件报告系统(Food and Drug Administration's adverse events reporting system,FAERS)数据库中PPIs/AGEP相关报告,采用比例失衡测量法及贝叶斯法对不同PPIs导致的AGEP进行关联性分析,并比较其发病时间及预后。结果共检索到此期间PPIs导致的AGEP病例报告162例。应用的PPIs药物主要为奥美拉唑(33.95%,55/162),其次为埃索美拉唑(29.63%,48/162)、泮托拉唑(26.54%,43/162)。以泮托拉唑与AGEP的关联性最强,其次为奥美拉唑和兰索拉唑,埃索美拉唑与AGEP的关联性较弱。PPIs导致AGEP发病时间的中位数为6(2,12)d,60.00%~83.33%的患者于用药后10 d内发病(除雷贝拉唑外)。3例(1.86%)AGEP患者死亡,128例(79.50%)需住院治疗。以埃索美拉唑导致的AGEP患者住院比率最高(91.49%,43/47),其次为泮托拉唑(88.37%,38/43)、兰索拉唑(85.71%,12/44),奥美拉唑(61.82%,34/55)最低。结论基于对FAERS数据库的药物警戒研究,揭示不同PPIs导致AGEP的风险及特点,可为临床合理用药提供依据。

Objective To explore and compare the associations of different proton pump inhibitors(PPIs)with acute generalized exanthematous pustulosis(AGEP).Methods Data were obtained from the da⁃tabase of Food and Drug Administration's adverse event reporting system(FAERS)from January 2004 to June 2020.Non⁃proportional analysis and Bayesian analysis were utilized to analyze the signs of AGEP caused by different PPIs.The onset time and prognosis of PPIs⁃related AGEP were also analyzed.Results A total of 162 cases of AGEP caused by PPIs were reported.The most frequently used PPI was omeprazole(33.95%,55/162),followed by esomeprazole(29.63%,48/162)and pantoprazole(26.54%,43/162).Pantoprazole showed the strongest correlation with AGEP,followed by omeprazole and lansoprazole,while esomeprazole ap⁃peared to have a weaker association with AGEP than other PPIs.The median time to the onset of AGEP was 6(2,12)days after PPI treatment,and 60.00%-83.33%of patients developed symptoms within 10 days after the medication(except rabeprazole).PPI⁃associated AGEP generally led to a fatality of 1.86%(3 cases)and a hospitalization rate of 79.50%(128 cases).The hospitalization rate of AGEP patients caused by omeprazole was the highest(91.49%,43/47),followed by that of pantoprazole(88.37%,38/43),lansoprazole(85.71%,12/44),and omeprazole(61.82%,34/55).Conclusions Our pharmacovigilance study based on the FAERS database demonstrated in detail the risks and characteristics of AGEP caused by different PPIs,which could provide a theoretical basis for rational clinical drug use.