Teach Stephen J, Gill Michelle A, Togias Alkis, Sorkness Christine A, Arbes Samuel J, Calatroni Agustin, Wildfire Jeremy J, Gergen Peter J, Cohen Robyn T, Pongracic Jacqueline A, Kercsmar Carolyn M, Khurana Hershey Gurjit K, Gruchalla Rebecca S, Liu Andrew H, Zoratti Edward M, Kattan Meyer, Grindle Kristine A, Gern James E, Busse William W, Szefler Stanley J
Division of Emergency Medicine and the Department of Pediatrics, Children's National Health System, Washington, DC.
Departments of Pediatrics and Immunology, University of Texas Southwestern Medical Center, Dallas, Tex.
J Allergy Clin Immunol. 2015 Dec;136(6):1476-1485. doi: 10.1016/j.jaci.2015.09.008. Epub 2015 Oct 27.
Short-term targeted treatment can potentially prevent fall asthma exacerbations while limiting therapy exposure.
We sought to compare (1) omalizumab with placebo and (2) omalizumab with an inhaled corticosteroid (ICS) boost with regard to fall exacerbation rates when initiated 4 to 6 weeks before return to school.
A 3-arm, randomized, double-blind, double placebo-controlled, multicenter clinical trial was conducted among inner-city asthmatic children aged 6 to 17 years with 1 or more recent exacerbations (clincaltrials.gov #NCT01430403). Guidelines-based therapy was continued over a 4- to 9-month run-in phase and a 4-month intervention phase. In a subset the effects of omalizumab on IFN-α responses to rhinovirus in PBMCs were examined.
Before the falls of 2012 and 2013, 727 children were enrolled, 513 were randomized, and 478 were analyzed. The fall exacerbation rate was significantly lower in the omalizumab versus placebo arms (11.3% vs 21.0%; odds ratio [OR], 0.48; 95% CI, 0.25-0.92), but there was no significant difference between omalizumab and ICS boost (8.4% vs 11.1%; OR, 0.73; 95% CI, 0.33-1.64). In a prespecified subgroup analysis, among participants with an exacerbation during the run-in phase, omalizumab was significantly more efficacious than both placebo (6.4% vs 36.3%; OR, 0.12; 95% CI, 0.02-0.64) and ICS boost (2.0% vs 27.8%; OR, 0.05; 95% CI, 0.002-0.98). Omalizumab improved IFN-α responses to rhinovirus, and within the omalizumab group, greater IFN-α increases were associated with fewer exacerbations (OR, 0.14; 95% CI, 0.01-0.88). Adverse events were rare and similar among arms.
Adding omalizumab before return to school to ongoing guidelines-based care among inner-city youth reduces fall asthma exacerbations, particularly among those with a recent exacerbation.
短期靶向治疗有可能预防秋季哮喘发作，同时限制治疗暴露。
我们试图比较（1）奥马珠单抗与安慰剂，以及（2）奥马珠单抗与吸入性糖皮质激素（ICS）强化治疗在返校前4至6周开始使用时的秋季发作率。
在6至17岁、近期有1次或更多次发作的市中心哮喘儿童中进行了一项三臂、随机、双盲、双安慰剂对照的多中心临床试验（临床研究注册号#NCT01430403）。在4至9个月的导入期和4个月的干预期内持续进行基于指南的治疗。在一个亚组中，研究了奥马珠单抗对PBMC中鼻病毒IFN-α反应的影响。
在2012年和2013年秋季之前，共纳入727名儿童，513名被随机分组，478名被分析。奥马珠单抗组的秋季发作率显著低于安慰剂组（11.3%对21.0%；优势比[OR]，0.48；95%可信区间[CI]，0.25 - 0.92），但奥马珠单抗与ICS强化治疗之间无显著差异（8.4%对11.1%；OR，0.73；95%CI，0.33 - 1.64）。在预先设定的亚组分析中，在导入期有发作的参与者中，奥马珠单抗比安慰剂（6.4%对36.3%；OR，0.12；95%CI，0.02 - 0.64）和ICS强化治疗（2.0%对27.8%；OR，0.05；95%CI，0.002 - 0.98）都显著更有效。奥马珠单抗改善了对鼻病毒的IFN-α反应，在奥马珠单抗组内，更大的IFN-α增加与更少的发作相关（OR，0.14；95%CI，0.01 - 0.88）。不良事件很少见，各治疗组相似。
在市中心青少年返校前，在基于指南的持续治疗中添加奥马珠单抗可减少秋季哮喘发作，特别是在近期有发作的患者中。
