Treatment Effect of Omalizumab on Severe Pediatric Atopic Dermatitis: The ADAPT Randomized Clinical Trial
Treatment Effect of Omalizumab on Severe Pediatric Atopic Dermatitis: The ADAPT Randomized Clinical Trial
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DOI：
10.1001/jamapediatrics.2019.4476
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发表时间：
2020-01-01
期刊：
影响因子：
26.1
通讯作者：
Lack, Gideon
中科院分区：
文献类型：
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作者：
Chan, Susan;Cornelius, Victoria;Lack, Gideon
严重儿童特应性皮炎的全身治疗证据有限和/或未经许可。尽管有效的抗IgE药物（omalizumab）在治疗特应性，在儿童特应性皮炎没有大的随机研究已经published.Objective确定omalizumab在治疗儿童严重特应性皮炎的有效性。设计、设置和参与者特应性皮炎抗IgE儿科试验（ADAPT）是一项为期24周的单中心、双盲、安慰剂对照随机临床试验，随访期为24周。本试验于2014年11月20日至2017年8月31日在英国Guy's and St托马斯医院NHS基金会信托基金会和伦敦国王学院进行，在筛选访视后招募受试者。符合条件的参与者（n=62）年龄为4至19岁，患有严重湿疹（客观特应性皮炎评分[SCORAD]指数>40），对最佳治疗无反应。统计分析采用意向治疗原则进行。干预皮下注射奥马珠单抗或安慰剂24周。使用药物制造商的剂量表来确定基于总IgE的剂量（30-1500 IU/mL）和体重主要结果和指标治疗24周后的客观SCORAD指数。（平均[SD]年龄，10.3 [4.2]岁; 32例（52%）为男性）随机分配至omalizumab（n=30）或安慰剂（n=32）组。5名参与者退出治疗（安慰剂组4名[13%]，奥马珠单抗组1名[3%]）。第24周随访率为97%，第48周为98%。校正基线客观SCORAD指数、年龄和IgE水平后，第24周两组间客观SCORAD指数改善的平均差异为-6.9（95%CI，-12.2至-1.5; P= 0.01），显著支持奥马珠单抗治疗，并反映了特应性皮炎严重程度的其他评估结果。通过儿童皮肤病生活质量指数/皮肤病生活质量指数（-3.5; 95% CI，-6.4至-0.5）和儿童过敏性疾病生活质量问卷评分（-0.5; 95% CI，-0.9至-0.0）测量，在奥马珠单抗组中观察到生活质量评分改善。与安慰剂组相比，尽管奥马珠单抗组局部使用的强效皮质类固醇较少，但疾病严重程度仍有所改善（覆盖体表面积的中位数[四分位距（IQR）]百分比，16% [10%-46%] vs 31% [14%-55%];使用天数中位数[IQR]，109 [34-164]天vs 161 [82-171]天）结论和相关性这项随机临床试验发现，奥马珠单抗显著降低了特应性皮炎的严重程度，并改善了患有特应性和严重湿疹的儿童人群的生活质量，尽管奥马珠单抗对特应性皮炎和严重湿疹的治疗效果有很高的提高。基线总IgE水平。该结果与有效的局部皮质类固醇节省效应相关，并可能表明奥马珠单抗是特应性儿童难以管理的严重湿疹的治疗选择。
IMPORTANCE Systemic treatments for severe childhood atopic dermatitis have limited evidence and/or are unlicensed. Despite the efficacy of anti-IgE medication (omalizumab) in the treatment of atopy, no large randomized studies in childhood atopic dermatitis have been published.OBJECTIVE To determine the effectiveness of omalizumab in treating severe atopic dermatitis in children. Design, Setting, and Participants The Atopic Dermatitis Anti-IgE Pediatric Trial (ADAPT) was a 24-week single- center, double-blind, placebo-controlled randomized clinical trial with a 24-week follow-up. Conducted from November 20, 2014, to August 31, 2017, at Guy's and St Thomas' Hospital NHS Foundation Trust and King's College London in the United Kingdom, this trial recruited participants after a screening visit. Eligible participants (n=62) were aged 4 to 19 years and had severe eczema (with objective Scoring Atopic Dermatitis [SCORAD] index >40) that was unresponsive to optimum therapy. Statistical analysis was conducted using the intention-to-treat principle.INTERVENTIONS Subcutaneous omalizumab or placebo for 24 weeks. The drug manufacturer's dosing tables were used to determine the dosage based on total IgE (30-1500 IU/mL) and body weight (in kilograms) at randomization.MAIN OUTCOMES AND MEASURES Objective SCORAD index after 24 weeks of treatment.RESULTS In total, 62 children (mean [SD] age, 10.3 [4.2] years; 32 (52%) were male) were randomized to either omalizumab (n=30) or placebo (n=32). Five participants withdrew from treatment (4 [13%] from the placebo group, and 1 [3%] from the omalizumab group). Follow-up attendance was 97% at week 24 and 98% at week 48. After adjustment for baseline objective SCORAD index, age, and IgE level, the mean difference in objective SCORAD index improvement between groups at week 24 was -6.9 (95% CI, -12.2 to -1.5; P=.01), significantly favoring omalizumab therapy and reflecting the results in other assessments of atopic dermatitis severity. Improved quality-of-life scores were seen in the omalizumab group, as measured by the Children's Dermatology Life Quality Index/Dermatology Life Quality Index (-3.5; 95% CI, -6.4 to -0.5) and Pediatric Allergic Disease Quality of Life Questionnaire score (-0.5; 95% CI, -0.9 to -0.0). Improvements in disease severity occurred despite lower potent topical corticosteroid use in the omalizumab group compared with the placebo group (median [interquartile range (IQR)] percentage of body surface area covered, 16% [10%-46%] vs 31% [14%-55%]; median [IQR] number of days of use, 109 [34-164] days vs 161 [82-171] days).CONCLUSIONS AND RELEVANCE This randomized clinical trial found that omalizumab significantly reduced atopic dermatitis severity and improved quality of life in a pediatric population with atopy and severe eczema despite highly elevated total IgE levels at baseline. The result was associated with a potent topical corticosteroid sparing effect and may suggest that omalizumab is a treatment option for difficult-to-manage severe eczema in children with atopy.