Objective To investigate the safety of tocilizumab(TCZ)in the treatment of children with systemic juvenile idiopathic arthritis(sJIA).Methods Data of children aged 2 to 18 years with the diagnosis of sJIA and treated with TCZ from June 1,2017 to June 30,2022 at our hospital were retrospectively collected.The clinical medication characteristics,incidence,severity and outcome of adverse drug reactions(ADR)were statistically analyzed.Univariate and multivariate analysis were used to analyze the risk factors of TCZ-induced ADR.Univariate comparison between groups were compared to the measured data followed by t test for normal distribution,and the counting data were paired with Chi-square test.Binary logistic regression analysis was used for multivariate analysis.Results A total of 83 eligible children were enrolled.The age at TCZ initiation was(8.5±3.7)years old.Most of the children received oral glucocorticoid(86.8％)and/or methotrexate(72.3％)prior to TCZ treatment.The mean time of TCZ duration was(1.2±0.9)years,the total TCZ exposure was 92.70 patient years.Fifty-five(66.3％)children reported 123 ADR,with a rate of 132.69/100 patient years.Forty-two(50.6％)children reported 103 general ADR,with a rate of 111.11/100 patient years.Eighteen(21.7％)children reported 20 serious ADR,with a rate of 21.57/100 patient years.The results of univariate analysis showed that the dosage of glucocorticoid in ADR group was higher than that in non-ADR group[(0.76±0.50)mg·kg-1·d-1 vs.(0.52±0.41)mg·kg-1·d-1,t=2.27,P=0.026],and the difference was statistically significant.However,there were no significant differences in gender[(male 23,female 32)cases vs.(male 9,female 19)cases,x2=0.73,P=0.392],age at TCZ initiation[(8.5±3.8)years old vs.(9.0±3.1)years old,t=-0.65,P=0.516],duration of TCZ treatment[(1.24±1.00)years vs.(1.05±0.90)years,t=0.87,P=0.385],methotrexate doses weekly[(8.0±5.2)mg/m2 vs.(7.6±5.1)mg/m2,t=0.39,P=0.696],and history of drug or food allergy(11 cases vs.5 cases,x2=0.06,P=0.815)between the two groups.The results of binary logistic regression analysis showed that the combined use of oral glucocorticoids was an independent risk factor for TCZ-induced ADR[OR(95％CI)=3.05(1.11,8.36),P=0.030].The risk of ADR was 3.05 times higher in the combined daily dose of glucocorticoids ≥0.76 mg/kg prednisone equivalent than that of＜0.76 mg/kg.Common general ADR to TCZ include infections(38.83/100 patient years)and abnormalities in laboratory parameters(37.76/100 patient years)such as elevated glutamic-pyrupiane transaminase(18.34/100 patient years),dyslipidemia(12.94/100 patient years),and hemocytopenia(5.39/100 patient years).The serious ADR included serious infection(9.71/100 patient years)and serious infusion reaction(7.55/100 patient years).All ADR were improved after drug withdrawal or symptomatic treatment,and no deaths occurred.Conclusion TCZ has a good safety profile in the treatment of sJIA.Serious infections and severe infusion reactions often lead to discontinuation of the drug.The combination of glucocorticoids ≥0.76 mg/kg prednisone equivalent is an independent risk factor for TCZ-induced ADR.Monitoring should be strengthened during the application of TCZ,and ADR should be detected and treated as early as possible to reduce the risk of medication related adverse reactions.
Idiopathic arthritis,juvenilityAdverse drug reactionsTocilizumab
NETL
NSTL
万方数据
