Mining And Analysis Of Adverse Reaction Signals Of Epidermal Growth Factor Receptor Inhibitors Based On The FAERS Database

Objective New risk signals were expected to be discovered by re-evaluating the safety of adverse event data of epithelial growth factor receptor inhibiters(EGFRIs)after marketing based on the FDA Adverse Event Reporting System(FAERS)database,in order to promote the rational use of EGFRIs in clinical practice and provide reference for safe use.Methods The adverse event reports of epidermal growth factor receptor inhibitors(EGFRIs)(including cetuximab,panizumab,gefitinib and erlotinib,etc)received in the FAERS database of the FDA adverse event reporting system from the first quarter of 2013 to the second quarter of 2021 in a total of 34 quarters were collected.The adverse drug event(ADE)reports were statistically described from the perspective of annual reporting trend,gender and age of patients and clinical outcomes.The reported ratio ratio(ROR)and the proportional reported ratio(PRR)in the proportional imbalance method were used to mine and analyze the data in the FAERS database,detect the safety signals of the above drugs,and analyze the key involved organs and high-risk signals.Results The FAERS database reported 30728493 adverse events from 2013 to2021.After data processing,10567338 cases remained,including 8450 cases of cetuximab as the first suspected drug,5292 cases of panizumab,149 cases of necitumumab,3035 cases of gefitinib,22182 cases of erlotinib,4689 cases of afatinib,209 cases of dactinib and 10236 cases of ositinib.After data mining,effective signals of the drug were found,including 344 cetuximab,277 panizumab,20 necitumumab,137 gefitinib,329 erlotinib,250 afatinib,22 dactinib and 229 g ositinib;among them,there were 735693 adverse cardiac events,and the effective signals were cetuximab [ROR=1.17,95% CI(1.08,1.28)],netizumab [ROR=2.94,95% CI(1.61,5.36)],dactinib[ROR=3.73,95% CI(2.10,6.62)],and ositinib [ROR=1.61,95% CI(1.50,1.72)];Monoclonal antibodies are more likely to cause tachycardia,and all cardiac related effective signals of TKIs include pericardial effusion.The significant death signals are panizumab [ROR=1.71,95% CI(1.54,1.89)],gefitinib[ROR=2.93,95% CI(2.64,3.25)],erlotinib [ROR=6.72,95% CI(6.54,6.91)],afatinib [ROR=1.30,95% CI(1.17,1.45)],dactinib [ROR=14.24,95% CI(11.27,17.99)],and ositinib [ROR=15.03,95% CI(14.53,15.54)].Conclusions EGFR inhibitors can lead to different adverse reactions,involving multiple systems and organs,mainly including skin and subcutaneous tissue,respiratory system,chest and mediastinum,gastrointestinal system,etc.The clinical outcome of adverse reactions of EGFR inhibitors is relatively serious,which needs to be paid enough attention to in clinic.EGFR inhibitors can cause cardiac adverse events.At the system organ level,the cardiac related adverse event signals that are significant involve cetuximab,necituzumab,dactinib,and ositinib.There are more cases and more cardiac related effective signals of cetuximab and ositinib,reflecting their greater cardiotoxicity.Monoantibodies are more likely to cause tachycardia.All cardiac related effective signals of TKIs include pericardial effusion,and other drugs may also have potential cardiac toxicity;Among the eight drugs of EGFR inhibitors,except cetuximab and necituzumab,other EGFR inhibitors are at risk of death due to drug use.