Kingsbury Daniel J, Bader-Meunier Brigitte, Patel Gina, Arora Vipin, Kalabic Jasmina, Kupper Hartmut
Randall Children's Hospital at Legacy Emanuel, 501 N Graham, Suite 355, Portland, OR, 97227, USA,
Clin Rheumatol. 2014;33(10):1433-41. doi: 10.1007/s10067-014-2498-1. Epub 2014 Feb 2.
The objective of this study was to assess the safety of adalimumab in patients aged 2 to <4 years old or ≥4 years old weighing <15 kg with moderately to severely active polyarticular juvenile idiopathic arthritis (JIA). Clinical effectiveness and pharmacokinetics (PK) of adalimumab were also evaluated. This was an international, multicenter, open-label, phase 3b study in 32 patients with active JIA that were treated with adalimumab 24 mg/m(2) (maximum = 20 mg/dose) every other week up to 120 weeks, with or without concomitant methotrexate. Adverse events (AEs) were summarized for completed visits. Efficacy endpoints included American College of Rheumatology pediatric (PedACR) 30/50/70/90 responses and JIA core components. Adalimumab serum trough concentrations were measured in a subset of patients. Among the patients, 88 % were female. Baseline mean age, weight, and JIA duration were 3 years, 13 kg, and 12 months, respectively; 39 % had elevated C-reactive protein. AE incidence rates included any AEs (29/32, 91 %), serious AEs (5/32, 16 %), infectious AEs (25/32, 78 %), and serious infections (3/32, 9 %). No deaths, malignancies, or opportunistic infections were reported. Growth was not adversely impacted. At week 96, 92 % of patients achieved PedACR30, and 77 % achieved PedACR70. Improvements in JIA core components were observed. Mean steady-state serum adalimumab trough concentrations were 7-8 μg/mL at weeks 12 and 24. Adalimumab was well tolerated in JIA patients aged 2 to <4 years old or ≥4 years old weighing <15 kg. The efficacy and PK of adalimumab were comparable to those seen in older JIA patients.
本研究的目的是评估阿达木单抗在年龄为2至<4岁或≥4岁且体重<15 kg的中度至重度活动性多关节型幼年特发性关节炎（JIA）患者中的安全性。同时还评估了阿达木单抗的临床疗效和药代动力学（PK）。这是一项国际多中心、开放标签的3b期研究，入组了32例活动性JIA患者，每两周接受一次24 mg/m²（最大剂量=20 mg/剂）的阿达木单抗治疗，疗程长达120周，部分患者联合使用甲氨蝶呤。对完成访视的不良事件（AE）进行总结。疗效终点包括美国风湿病学会儿科（PedACR）30/50/70/90反应以及JIA核心指标。在部分患者中测定了阿达木单抗的血清谷浓度。患者中88%为女性。基线时平均年龄、体重和JIA病程分别为3岁、13 kg和12个月；39%的患者C反应蛋白升高。AE发生率包括任何AE（29/32，91%）、严重AE（5/32，16%）、感染性AE（25/32，78%）和严重感染（3/32，9%）。未报告死亡、恶性肿瘤或机会性感染。生长未受到不利影响。在第96周时，92%的患者达到PedACR30，77%的患者达到PedACR70。观察到JIA核心指标有所改善。在第12周和第24周时，阿达木单抗的平均稳态血清谷浓度为7 - 8 μg/mL。阿达木单抗在年龄为2至<4岁或≥4岁且体重<15 kg的JIA患者中耐受性良好。阿达木单抗的疗效和PK与年龄较大的JIA患者相当。
