英夫利西单抗治疗儿童克罗恩病效果及安全性分析

Efficacy and safety of infliximab in the treatment of pediatirc Crohn′s disease

目的分析英夫利西单抗(IFX)治疗儿童克罗恩病的效果以及安全性。方法回顾性分析2007年1月至2017年12月在上海瑞金医院儿科、上海瑞金医院北院区儿科以及上海交通大学附属儿童医院消化科接受IFX治疗的86例克罗恩病患儿临床资料,分析治疗前后临床资料和实验室数据,评估IFX疗效,组间比较采用t检验、秩和检验或χ^(2)检验;采用单因素和多因素Logistic回归分析患儿年龄、临床特征、疾病行为及合并用药等因素对IFX疗效及安全性的影响。结果86例克罗恩病患儿中男50例、女36例,首次IFX治疗年龄为12.0(7.1,13.6)岁,随访时间为94.1(47.8,185.5)周。疗效分析显示,诱导缓解期临床应答率为97%(79/81),缓解率为74%(60/81);维持缓解期临床应答率为75%(51/68),缓解率为68%(46/68)。患儿IFX治疗第34周儿童克罗恩病活动指数(PCDAI)[5(0,10)比36(26,45)分]、C反应蛋白[3(1,8)比8(3,31)mg/L]、红细胞沉降率[10(6,10)比35(20,50)mm/1 h]、血小板计数[(327±107)×10^(9)比(438±159)×10^(9)/L]、白蛋白[(37±6)比(30±6)g/L]、血红蛋白[(116±16)比(103±18)g/L]、体重Z值(-0.5±1.2比-1.0±0.9)、贫血比例[29%(20/68)比75%(51/68)]、肛周病变愈合比例(13/21比0)均有显著改善(均P<0.05)。IFX治疗至34周有25%(17/68)患儿发生继发性失应答,多因素Logistic回归分析显示PCDAI>30分与继发性失应答正相关(OR=3.823,95%CI 1.015~15.328,P=0.048),合并硫唑嘌呤有利于IFX持续有效(OR=0.440,95%CI 0.106~1.033,P=0.044)。IFX输液反应发生率为17%(15/86),治疗期间感染发生率为42%(36/86)。单因素分析发现年龄<6岁是发生输液反应的高危因素(χ^(2)=6.556,P=0.010),合并使用激素(χ^(2)=5.230,P=0.022)可能会增加感染发生。结论IFX对儿童克罗恩病疗效显著且相对安全,减少继发性失应答是亟待解决的问题,同时治疗期间需警惕不良事件的发生并及时处理。

Objective To analyze the efficacy and safety of the biological agent infliximab(IFX)in the treatment of pediatric Crohn′s disease.Methods A total of 86 children with Crohn′s disease who had received IFX in three hospitals(Ruijin Hospital,Ruijin Hospital North and Shanghai Children's Hospital)in Shanghai from January 2007 to December 2017 were included in this retrospective study.The efficacy of IFX was assessed by comparing clinical and laboratory data before and after IFX treatment.Student t test,Mann-Whitney U test or chi-square test were used to analyze the data of the two groups.Logistic reggression analysis were used to analyze the effects of variables such as age,clinical characteristics,disease behavior and combined medications on the efficacy and safety of IFX.Results Among the 86 children with Crohn′s disease in the study,50 were males and 36 females.The IFX treatment was initiated at 12.0(7.1,13.6)years of age,and the follow-up period was 94.1(47.8,185.5)weeks.Efficacy analysis showed that in the induction remission phase,the clinical response rate was 97%(79/81)and the remission rate was 74%(60/81).In the maintenance remission phase,the clinical response rate was 75%(51/68)and the remission rate was 68%(46/68).After 34 weeks of treatment with IFX,pediatric Crohn′s disease activity index(PCDAI)(5(0,10)vs.36(26,45)),C-reactive protein(3(1,8)vs.8(3,31)mg/L),erythrocyte sedimentation rate(10(6,10)vs.35(20,50)mm/1 h),platelet((327±107)×10^(9)vs.(438±159)×10^(9)/L),albumin((37±6)vs.(30±6)g/L),hemoglobin((116±16)vs.(103±18)g/L),change of body weight(-0.5±1.2 vs.-1.0±0.9),anemia(29%(20/68)vs.75%(51/68)),and perianal disease(13/21 vs.0)were significantly improved(all P<0.05).By the end of 34 weeks of IFX treatment,25%(17/68)of children experienced secondary loss of response to IFX.Logistic reggression analysis showed that PCDAI>30 was positively correlated with secondary loss of response(OR=3.823,95%CI 1.015-15.328,P=0.048),and combined with azathioprine was conducive to maintaining efficacy of IFX(OR=0.440,95%CI 0.106-1.033,P=0.044).The IFX-related adverse events included infusion reactions in 17%(15/86)and infections in 42%(36/86)of children.Analysis showed that age<6 years was a risk factor for infusion reactions(χ^(2)=6.556,P=0.010),and combined use of steroids(χ^(2)=5.230,P=0.022)may increase the incidence of infection.Conclusions IFX is effective in the treatment of pediatric Crohn′s disease with favorable safety.Reducing secondary loss of response to IFX is an urgent issue that need to be addressed.At the same time,it is necessary to pay close attention to the adverse events during IFX treatment.