托珠单抗和肿瘤坏死因子α抑制剂及改善病情抗风湿药物治疗全身型幼年特发性关节炎的临床效果

摘要

Objective To analyze clinical effect of tocilizumab,tumor necrosis factor α (TNF-α)inhibitors and disease-modifying anti-rheumatic drugs (DMARDs) on systemic-onset juvenile idiopathic arthritis (SoJIA).Methods Totally 30 children with SoJIA from December 2013 to December 2015 in Shenzhen Children's Hospital were randomly divided into tocilizumab group(10 cases),TNF-o inhibitors group(10 cases)and DMARDs group(10 cases).The tocilizumab group was treated with tocilizumab and methotrexate;the TNF-α inhibitors group was treated with TNF-α inhibitors and methotrexate;the DMARDs group was treated with DMARDs and glucocorticoid or non-steroidal anti-inflammatory drugs.After 3 and 6 months of treatment,joint pain index,joint swelling index,recurrent fever time and erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),serum ferritin(SF),American College of Rheumatology(ACR) 30 improvement rate and ACR 50 improvement rate were analyzed.Adverse reactions were observed.Results After 3 and 6 months of treatment,joint pain indexes,joint swelling indexes,recurrent fever times and levels of ESR,CRP,SF were all significantly lower than those before treatment in 3 groups [DMARD group:(2.19 ± 0.22),(1.39 ± 0.42) scores vs (2.45 ± 0.21)scores;(2.5±0.5),(2.0±0.3)scores vs (3.5±0.3)scores;(2.67±0.21),(2.06±0.33)months vs (3.78 ± 1.65)months;(61 ± 15),(45 ± 12) mm/1 h vs (84 ± 17) mm/1 h;(69 ± 10),(44 ± 14)mg/L vs (85 ±17)mg/L;(866 ±265),(639 ±96)mg/L vs (2 522 ± 1 686) mg/L;TNF-α inhibitor group:(1.83 ±0.35),(1.02 ± 0.17) scores vs (2.34 ± 0.26) scores;(2.0 ± 0.5),(1.5 ± 0.3) scores vs (3.3 ± 0.3) scores;(1.53±0.36),(1.62±0.24)months vs (3.66 ±1.52)months;(44±12),(34±9)mm/1 h vs (82±19)mm/1 h;(54±15),(30 ± 11) mg/L vs (87 ± 19) mg/L;(574 ± 164),(464 ± 81)mg/L vs (2 496 ±1 826) mg/L;Tocilizumab group:(1.65 ± 0.34),(0.74 ± 0.20) scores vs (2.23 ± 0.25) scores;(1.6 ± 0.4),(0.8 ± 0.5) scores vs (3.4 ± 0.4) scores;(1.63 ± 0.27),(0.80 ± 0.29) months vs (3.56 ± 1.76) months;(40 ± 13),(24± 10)mm/1 h vs (84 ± 19)mm/1 h;(49 ± 12),(15 ± 8)mg/L vs (87 ± 18)mg/L;(478 ±168),(273 ± 62) mg/L vs (2 563 ± 1 765) mg/L] (P ＜ 0.05).After 6 months of treatment,joint pain index,swelling index,recurrent fever time and ESR,CRP,SF levels in tocilizumab group were significantly better than those in TNF-α inhibitors group and DMARDs group (P ＜ 0.05);ACR 30 and ACR 50 improvement rates in tocilizumab group and TNF-α inhibitors group were significantly higher than those in DMARDs group,and ACR 30and ACR 50 improvement rates in tocilizumab group were significantly higher than those in TNF-α inhibitors group (P ＜ 0.05).All adverse reactions were mild-to-moderate and transient,including 1 case of infusion reaction in tocilizumab group,1 case of acute upper respiratory tract infection and 1 case of injection site pain in TNF-αinhibitors group,and 3 cases of gastrointestinal reaction in DMARDs group;adverse reactions were improved after symptomatic treatments.Conclusion In the treatment of SoJIA,tocilizumab is more effective and safer than TNF-α inhibitors and DMARDs.%目的 比较托珠单抗和肿瘤坏死因子0(TNF-α)抑制剂及改善病情抗风湿药物(DMARDs)治疗全身型幼年特发性关节炎(So-JIA)的临床效果.方法 选取2013年12月至2015年12月在广东省深圳市儿童医院确诊的初发活动期So-JIA患儿30例,按照随机数字表法分为托珠单抗组(10例)、TNF-α抑制剂组(10例)和DMARDs组(10例).托珠单抗组单用托珠单抗或联合甲氨蝶呤治疗;TNF-α抑制剂组使用TNF-α抑制剂联合甲氨蝶呤治疗;DMARDs组使用DMARDs联合糖皮质激素或非甾体消炎药治疗.比较3组患儿治疗前和治疗3、6个月的关节疼痛指数、关节肿胀指数、反复发热时间和红细胞沉降率(ESR)、C反应蛋白(CRP)、血清铁蛋白(SF)水平;比较3组患儿治疗3、6个月的美国风湿病学会(ACR) 30改善和ACR 50改善率;记录3组不良反应发生情况.结果 3组治疗3、6个月关节疼痛指数、关节肿胀指数、反复发热时间和ESR、CRP、SF与治疗前比较均明显改善[DMARDs组:(2.19±0.22)、(1.39±0.42)分比(2.45±0.21)分,(2.5±0.5)、(2.0±0.3)分比(3.5±0.3)分,(2.67 ±0.21)、(2.06±0.33)个月比(3.78±1.65)个月,(61 ±15) 、(45±12)mm/1 h比(84±17) mm/1 h,(69±10)、(44±14) mg/L比(85±17) mg/L,(866±265)、(639±96) mg/L比(2 522±1 686) mg/L;TNF-α抑制剂组:(1.83±0.35)、(1.02±0.17)分比(2.34±0.26)分,(2.0±0.5)、(1.5±0.3)分比(3.3±0.3)分,(1.53±0.36)、(1.62±0.24)个月比(3.66±1.52)个月,(44±12)、(34 ±9) mm/1 h比(82±19)mm/1 h,(54±15)、(30±11)mg/L比(87±19) mg/L,(574±164)、(464 ±81)mg/L比(2 496±1 826) mg/L;托珠单抗组:(1.65±0.34)、(0.74±0.20)分比(2.23±0.25)分,(1.6±0.4)、(0.8±0.5)分比(3.4±0.4)分,(1.63±0.27)、(0.80±0.29)个月比(3.56±1.76)个月,(40±13)、(24±10) mm/1 h比(84±19) mm/1 h,(49±12)、(15 ±8) mg/L比(87±18) mg/L,(478±168)、(273±62) mg/L比(2 563±1 765) mg/L];治疗6个月,托珠单抗组关节疼痛指数、关节肿胀指数、反复发热时间和ESR 、CRP、SF均优于TNF-α抑制剂组及DMARDs组,差异均有统计学意义(均P＜0.05).治疗6个月,托珠单抗组和TNF-α抑制剂组ACR 30改善率和ACR 50改善率均明显高于DMARDs组,且托珠单抗组明显优于TNF-0抑制剂组,差异均有统计学意义(均P＜0.05).托珠单抗组出现输液反应1例;TN F-α抑制剂组出现急性上呼吸道感染1例、注射部位肿痛1例;DMARDs组出现胃肠道反应3例.3组不良反应均为轻中度、暂时性,予对症处理后均好转.结论 托珠单抗治疗So-JIA效果明显优于TNF-α抑制剂及DMARDs,起效快,安全性好.