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| Efficacy and safety of humanized interleukin-6 receptor antibody in treatment of systemic juvenile idiopathic arthritis |
| ZOU Lixia, LU Meiping, GUO Li, TENG Liping, XU Yiping, ZHENG Qi |
| Department of Rheumatology, Immunology & Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China |
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Abstract Objective:To evaluate the efficacy and safety of humanized anti-IL-6 receptor monoclonal antibody (tocilizumab) in treatment of systemic juvenile idiopathic arthritis (sJIA). Methods:Thirteen sJIA patients admitted between December 2015 and November 2016 and received tocilizumab treatment were enrolled in the study. The complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6) and ferritin levels were measured; American College of Rheumatology Pediatric(ACR Pedi)30/50/70/90 scores were assessed; and the use of glucocorticosteroid and adverse events were documented. Results:Compared with the baseline levels, the CRP and ESR at d3 were decreased (all P<0.05); hemoglobin was increased and platelet was decreased at week 2 (all P<0.05), ferritin decreased at week 4, white blood cell (WBC) decreased at week 8 after treatment with tocilizumab (all P<0.05). The level of IL-6 was rising at d3 and week 2 and descending at week 4, but no significant difference was observed compared with the baseline level (all P>0.05). All 13 patients achieved ACR Pedi 30 remission at week 4, 61.5% achieved ACR Pedi 90 remission and glucocorticosteroids were withdrawn at week 20. Twenty two adverse events occurred, and infection accounted for 54.5% (12/22); no severe adverse reactions were observed during 20-week follow-up. Conclusion:Tocilizumab is safe and effective in treatment of sJIA, with decreasing inflammation, improving disease activity and reducing glucocorticosteroid use.
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Received: 01 April 2017
Published: 25 August 2017
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人源化白细胞介素-6受体抗体治疗全身型幼年特发性关节炎的疗效及安全性
目的：探讨人源化IL-6受体抗体（托珠单抗注射液）治疗全身型幼年特发性关节炎（sJIA）的临床疗效及安全性。方法：回顾性分析2015年12月-2016年11月在浙江大学医学院附属儿童医院应用托珠单抗治疗的13例sJIA患儿的临床资料，包括血常规、C反应蛋白（CRP）、红细胞沉降率（ESR）、IL-6、血清铁蛋白、美国风湿病学儿科（ACR Pedi）30/50/70/90评分、激素使用情况以及治疗期间的不良反应。结果：与治疗前比较，治疗后第3天患儿的CRP和ESR明显下降（均P<0.05）；治疗后第2周血红蛋白增加和血小板减少（均P<0.05）；第4周血清铁蛋白水平下降（P<0.05）；白细胞在治疗后第8周时减少（P<0.05）。IL-6水平在治疗后先上升，第4周时下降，但与治疗前比较差异均无统计学意义（均P>0.05）。治疗第4周ACR Pedi 30或以上达100%；第20周时，61.5%的患儿达到ACR Pedi 90和停用糖皮质激素。随访至20周，所有患儿共发生不良反应22例次，其中感染发生率占54.5%（12/22），无严重不良反应发生。结论：托珠单抗能快速控制sJIA炎症，改善疾病活动度，有助于糖皮质激素的顺利减量及停药，且安全有效。
关键词：
关节炎,
幼年型类风湿/药物疗法,
糖皮质激素类/治疗应用,
白细胞介素6,
抗体,
单克隆/治疗应用,
治疗结果,
安全性
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| [1] VAN DIJKHUIZEN E H, WULFFRAAT N M. Prediction of methotrexate efficacy and adverse events in patients with juvenile idiopathic arthritis:a systematic literature review[J/OL]. Pediatr Rheumatol Online J,2014,12:51.
[2] HORNEFF G, DE BOCK F, FOELDVARI I, et al.Safety and efficacy of combination of etanercept and methotrexate compared to treatment with etanercept only in patients with juvenile idiopathic arthritis (JIA):preliminary data from the German JIA Registry[J]. Ann Rheum Dis,2009,68(4):519-525.
[3] OLDFIELD V, DHILLON S, PLOSKER G L. Tocilizumab:a review of its use in the management of rheumatoid arthritis[J]. Drugs,2009,69(5):609-632.
[4] PETTY R E, SOUTHWOOD T R, MANNERS P, et al. International league of associations for rheumatology classification of juvenile idiopathic arthritis:second revision, Edmonton, 2001[J]. J Rheumatol,2004,31(2):390-392.
[5] RAVELLI A, MARTINI A. Juvenile idiopathic arthritis[J]. Lancet,2007,369(9563):767-778.
[6] DE BENEDETTI F, MASSA M, ROBBIONI P, et al.Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis[J]. Arthritis Rheum,1991,34(9):1158-1163.
[7] DE JAGER W, HOPPENREIJS E P, WULFFRAAT N M, et al. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis:a cross-sectional study[J]. Ann Rheum Dis,2007,66(5):589-598.
[8] NEMETH E, RIVERA S, GABAYAN V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin[J]. J Clin Invest,2004,113(9):1271-1276.
[9] ZHANG X, MORCOS P N, SAITO T, et al.Clinical pharmacology of tocilizumab for the treatment of systemic juvenile idiopathic arthritis[J]. Expert Rev Clin Pharmacol,2013,6(2):123-137.
[10] FRAMPTON J E. Tocilizumab:a review of its use in the treatment of juvenile idiopathic arthritis[J]. Paediatr Drugs,2013,15(6):515-531.
[11] YOKOTA S, IMAGAWA T, MORI M, et al.Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis:a randomised, double-blind, placebo-controlled, withdrawal phase Ⅲ trial[J]. Lancet,2008,371(9617):998-1006.
[12] SENCHENKOVA E Y, KOMOTO S, RUSSELL J, et al. Interleukin-6 mediates the platelet abnormalities and thrombogenesis associated with experimental colitis[J]. Am J Pathol,2013,183(1):173-181.
[13] LOVELL D J, GIANNINI E H, REIFF A, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group[J]. N Engl J Med,2000,342(11):763-769.
[14] DAVIES R, GAYNOR D, HYRICH K L, et al. Efficacy of biologic therapy across individual juvenile idiopathic arthritis subtypes:a systematic review[J]. Semin Arthritis Rheum,2017,46(5):584-593.
[15] 史群,尤欣,郑乐婷,等.白介素-6受体拮抗剂对类风湿关节炎患者外周血单个核细胞Th17分化的影响[J].中日友好医院学报,2013,27(3):159-163. SHI Qun,YOU Xin,ZHENG Leting, et al. The influence of interleukin-6 receptor antagonist to differentiation of Th17 peripheral blood mononuclear cells in patients with rheumatoid arthritls[J]. Journal of China-Japan Friendship Hospital,2013,27(3):159-163.(in Chinese)
[16] SHIMAMOTO K, ITO T, OZAKI Y, et al.Serum interleukin 6 before and after therapy with tocilizumab is a principal biomarker in patients with rheumatoid arthritis[J]. J Rheumatol,2013,40(7):1074-1081.
[17] DE BENEDETTI F, BRUNNER H I, RUPERTO N, et al.Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis[J]. N Engl J Med,2012,367(25):2385-2395.
[18] YOKOTA S, IMAGAWA T, MORI M, et al. Long-term treatment of systemic juvenile idiopathic arthritis with tocilizumab:results of an open-label extension study in Japan[J]. Ann Rheum Dis,2013,72(4):627-628.
[19] KOSTIK M M, DUBKO M F, MASALOVA V V, et al.Successful treatment with tocilizumab every 4 weeks of a low disease activity group who achieve a drug-free remission in patients with systemic-onset juvenile idiopathic arthritis[J/OL]. Pediatr Rheumatol Online J,2015,13:4.
[20] YOKOTA S, IMAGAWA T, MORI M, et al.Longterm safety and effectiveness of the anti-interleukin 6 receptor monoclonal antibody tocilizumab in patients with systemic juvenile idiopathic arthritis in Japan[J]. J Rheumatol,2014,41(4):759-767.
[21] BRUNNER H I, RUPERTO N, ZUBER Z, et al. Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis:results from a phase 3, randomised, double-blind withdrawal trial[J]. Ann Rheum Dis,2015,74(6):1110-1117.
[22] MARITSI D N, ONOUFRIOU M, VARTZELIS G, et al. Complete clinical remission with tocilizumab in two infants with systemic juvenile idiopathic arthritis:a case series[J]. Scand J Rheumatol,2017,46(1):75-76. |
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