新型冠状病毒感染患者使用托珠单抗后发生不良反应的病例分析

Adverse reactions in patients with COVID-19 after using tocilizumab

目的 探索新型冠状病毒感染患者使用托珠单抗导致药品不良反应(ADR)的特点,为临床安全用药提供参考。方法 回顾性分析2022年12月1日至2023年1月31日在本院使用托珠单抗治疗新冠后发生ADR的病例,总结托珠单抗引起的ADR特点;系统检索国内外数据库,收集从建库至2023年1月31日托珠单抗导致ADR的病例报道,对纳入病例的高危因素、给药方案、其他新型冠状病毒感染用药、ADR特点及临床结局等进行分析。结果 本院使用托珠单抗共48例新型冠状病毒感染患者,7例于用药后5[四分位距(IQR)1~7]d左右发生ADR,包括6例次(85.74%)血小板减少、3例次(42.86%)感染、1例次(14.29%)肝功能异常。住院中位时长为19(IQR 16~41)d,4例(57.14%)患者在住院期间死亡。文献检索纳入14篇病例报道,共计30例ADR,ADR在接受首剂托珠单抗后11(IQR4~14.5)d左右发生,包括16例次(53.33%)感染、9例次(30%)肝损伤、5例次(16.67%)肠溃疡/肠穿孔、3例次(10%)血小板减少等。患者住院中位时长为29(IQR 19~50)d,9例(30%)患者在住院期间死亡。结论 新型冠状病毒感染患者使用托珠单抗期间应警惕感染、肝损伤、血小板减少等ADR,及时对症治疗。

Objective To study the adverse drug reactions(ADR)caused by tocilizumab in patients with Corona Virus Disease 2019(COVID-19)and to provide clinical reference.Methods Cases of adverse drug reactions caused by tocilizumab between December 1,2022 and January 31,2023 in our hospital were retrospectively analyzed to summarize the characteristics of ADR associated with tocilizumab.Domestic and overseas databases were searched to collect the cases of ADR due to tocilizumab reported as of January 31,2023.The included patients were analyzed in terms of age,gender,weight,high-risk factors,types of COVID-19,time for administration of tocilizumab,regimens and durations,other drugs for COVID-19,onset time of adverse reactions,length of hospital stay and clinical outcomes.Results A total of 48 patients with COVID-19 were administered with tocilizumab,seven of whom experienced ADR within about 5[inter quartile range(IQR)1-7]days of dosing,including 6 cases of(85.74%)thrombocytopenia,3 cases of(42.86%)infections,and 1 case of(14.29%)liver function abnormalities.The median length of hospitalization was 19(IQR 16-41)days,and 4(57.14%)patients died during hospitalization.The literature search retrieved 14 case reports with a total of 30 COVID-19 patients with ADR induced by tocilizumab.ADR occurred about 11(IQR 4-14.5)days after the first dose of tocilizumab and included 16 cases of(53.33%)infections,9 cases of(30%)liver damage,5 cases of(16.67%)intestinal ulcers/enteric perforation,and 3 cases of(10%)thrombocytopenia.The median length of hospitalization of patients was 29(IQR 19-50)days and 9(30%)patients died during hospitalization.Conclusion Patients with COVID-19 should be alerted to ADR such as infections,liver damage,and thrombocytopenia during the use of tocilizumab.