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阿达木单抗联合甲氨蝶呤治疗幼年型特发性关节炎伴发的葡萄膜炎的研究
Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis


Athimalaipet V. Ramanan ... 妇产科和儿科 • 2017.04.27

摘要


背景

阿达木单抗是一种抗肿瘤坏死因子-α的全人源单克隆抗体,可以有效治疗幼年型特发性关节炎(juvenile idiopathic arthritis,JIA)。我们测试了阿达木单抗对JIA相关葡萄膜炎治疗的有效性。

 

方法

在本项多中心、双盲、随机、安慰剂对照试验中,我们评估了阿达木单抗对2岁或2岁以上患活动性JIA相关葡萄膜炎儿童和青少年的疗效和安全性。接受稳定剂量甲氨蝶呤治疗的患者以2∶1的比例被随机分配接受每2周一次皮下注射的阿达木单抗(20~40 mg,根据体重而定)或安慰剂。患者持续接受试验治疗方案,直至18个月或治疗失败。随机分配后,患者随访长达2年。主要终点为到治疗失败(使用由多个部分组成的眼内炎症评分进行定义,该评分是基于葡萄膜炎命名标准化[Standardization of Uveitis Nomenclature,SUN]标准)的时间。

 

结果

原计划招募114例患者,在第90例患者纳入本试验后,试验达到了预先设定的停止标准。我们观察到,使用阿达木单抗的60例患者中有16例治疗失败(27%);对比安慰剂组,30例患者中有18例治疗失败(60%)(风险比为0.25;95%置信区间[CI]为0.12~0.49;P<0.0001 [预先设定的停止边界])。接受阿达木单抗治疗的患者比接受安慰剂治疗的患者不良事件更多发(10.07次/患者年[95% CI,9.26~10.89]对6.51次/患者年[95% CI,5.26~7.77])。严重不良事件也是如此(0.29次/患者年[95% CI,0.15~0.43]对0.19次/患者年[95% CI,0.00~0.40])。

 

结论

阿达木单抗对于正在服用稳定剂量甲氨蝶呤的患活动性JIA相关葡萄膜炎的儿童和青少年,可以控制其炎症并且治疗失败率低于安慰剂组。接受阿达木单抗的患者发生不良事件和严重不良事件的概率远高于安慰剂组(该研究由NIHR医疗技术评估项目[Health Technology Assessment Programme]和英国关节炎研究慈善团体[Arthritis Research UK]资助;SYCAMORE EudraCT注册号为2010-021141-41)。





作者信息

Athimalaipet V. Ramanan, F.R.C.P.C.H., F.R.C.P., Andrew D. Dick, M.B., B.S., M.D., Ashley P. Jones, Ph.D., Andrew McKay, M.Sc., Paula R. Williamson, Ph.D., Sandrine Compeyrot-Lacassagne, M.D., Ben Hardwick, M.Res., Helen Hickey, B.Sc., Dyfrig Hughes, Ph.D., Patricia Woo, F.Med.Sci., Diana Benton, M.A., Clive Edelsten, M.R.C.P., F.R.C.Ophth., and Michael W. Beresford, M.B., Ch.B., Ph.D., for the SYCAMORE Study Group*
From University Hospitals Bristol NHS Foundation Trust (A.V.R., A.D.D., D.B.) and the School of Clinical Sciences, University of Bristol (A.V.R., A.D.D.), Bristol, National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology (A.D.D., P.W.) and Great Ormond Street Hospital (S.C.-L., C.E.), London, Institute of Translational Medicine, University of Liverpool (A.P.J., A.M., P.R.W., B.H., H.H., M.W.B.), and the Department of Paediatric Rheumatology, Alder Hey Children’s NHS Foundation Trust (M.W.B.), Liverpool, and Bangor University, Bangor (D.H.) — all in the United Kingdom. Address reprint requests to Dr. Ramanan at the Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, Bristol BS2 8BJ, United Kingdom, or at avramanan@hotmail.com. *A complete list of the investigators in the SYCAMORE Study Group is provided in the Supplementary Appendix, available at NEJM.org.

 

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