Thaçi D, Papp K, Marcoux D, Weibel L, Pinter A, Ghislain P-D, Landells I, Hoeger P H, Unnebrink K, Seyger M M B, Williams D A, Rubant S, Philipp S
Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Ratzeburger Allee 160, 23435, Lübeck, Germany.
K Papp Clinical Research and Probity Medical Research, University of Western Ontario, Waterloo, ON, Canada.
Br J Dermatol. 2019 Dec;181(6):1177-1189. doi: 10.1111/bjd.18029. Epub 2019 Jul 25.
Adalimumab (ADA) (Humira , AbbVie Inc., U.S.A.) is approved by the European Medicines Agency for children aged ≥ 4 years with severe plaque psoriasis.
To evaluate the long-term efficacy and safety of ADA in children with severe plaque psoriasis.
Results are presented from the 52-week long-term extension (LTE) of the randomized, double-blind, double-dummy, phase III trial, in children with severe plaque psoriasis (results from prior periods have been published). Patients aged ≥ 4 and < 18 years were randomized 1 : 1 : 1 to ADA 0·8 mg kg (40 mg maximum) or 0·4 mg kg (20 mg maximum) every other week or to methotrexate (MTX) 0·1-0·4 mg kg (25 mg maximum) weekly. The 16-week initial treatment (IT) period was followed by a 36-week withdrawal period and a 16-week retreatment period. Patients could enter the LTE at prespecified time points to receive ADA 0·8 mg kg (blinded or open label) or ADA 0·4 mg kg (blinded), or to remain off treatment. Efficacy is reported for patient groups according to doses received in the IT and LTE periods.
Of the 114 patients randomized in the IT period, 108 entered the LTE (n = 36 in each group); 93 received ADA 0·8 mg kg . Efficacy (≥ 75% improvement from baseline in Psoriasis Area and Severity Index) was maintained or improved from entry to the end of the LTE: MTX(IT)/ADA 0·8(LTE) 31-86% of patients; ADA 0·4(IT)/0·4 or 0·8(LTE) 28-47%; ADA 0·8(IT)/0·8(LTE) 50-72%. No serious infections occurred in the LTE.
After 52 weeks of long-term ADA treatment in children aged 4-18 years with severe plaque psoriasis, disease severity was reduced and maintained or further improved, as demonstrated by efficacy outcomes. No new safety risks were identified. What's already known about this topic? The results from the first three periods of this phase III trial in children aged 4-18 years with severe plaque psoriasis suggest that adalimumab is a safe and efficacious treatment option in this population. What does this study add? This is the first study to evaluate long-term treatment of adalimumab in children with severe psoriasis, and the first to evaluate switching from methotrexate to adalimumab in this population.
阿达木单抗（ADA）（修美乐，艾伯维公司，美国）已获欧洲药品管理局批准用于治疗年龄≥4岁的重度斑块状银屑病儿童。
评估ADA治疗重度斑块状银屑病儿童的长期疗效和安全性。
本文给出了一项针对重度斑块状银屑病儿童的随机、双盲、双模拟III期试验52周长期延长期（LTE）的结果（前期结果已发表）。年龄≥4岁且<18岁的患者按1∶1∶1随机分组，分别接受每两周一次的ADA 0.8 mg/kg（最大剂量40 mg）或0.4 mg/kg（最大剂量20 mg），或每周一次的甲氨蝶呤（MTX）0.1 - 0.4 mg/kg（最大剂量25 mg）。16周的初始治疗（IT）期之后是36周的撤药期和16周的再治疗期。患者可在预先指定的时间点进入LTE，接受ADA 0.8 mg/kg（盲法或开放标签）或ADA 0.4 mg/kg（盲法），或继续停药。根据患者在IT期和LTE期接受的剂量报告各患者组的疗效。
在IT期随机分组的114例患者中，108例进入LTE（每组36例）；93例接受ADA 0.8 mg/kg。从进入LTE开始到LTE结束，疗效（银屑病面积和严重程度指数较基线改善≥75%）得以维持或提高：MTX（IT）/ADA 0.8（LTE）组为31% - 86%的患者；ADA 0.4（IT）/0.4或0.8（LTE）组为28% - 47%；ADA 0.8（IT）/0.8（LTE）组为50% - 72%。LTE期未发生严重感染。
在4 - 18岁重度斑块状银屑病儿童中进行52周的ADA长期治疗后，疾病严重程度降低且得以维持或进一步改善，疗效结果证明了这一点。未发现新的安全风险。关于该主题已知的信息有哪些？这项针对4 - 18岁重度斑块状银屑病儿童的III期试验前三个阶段的结果表明，阿达木单抗在该人群中是一种安全有效的治疗选择。本研究增加了什么内容？这是第一项评估阿达木单抗治疗重度银屑病儿童长期疗效的研究，也是第一项评估该人群从甲氨蝶呤转换为阿达木单抗治疗情况的研究。
