Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations.
Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations.
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DOI：
10.1016/j.jaci.2015.09.008
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发表时间：
2015-12
期刊：
影响因子：
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通讯作者：
Szefler SJ
中科院分区：
文献类型：
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作者：
Teach SJ;Gill MA;Togias A;Sorkness CA;Arbes SJ Jr;Calatroni A;Wildfire JJ;Gergen PJ;Cohen RT;Pongracic JA;Kercsmar CM;Khurana Hershey GK;Gruchalla RS;Liu AH;Zoratti EM;Kattan M;Grindle KA;Gern JE;Busse WW;Szefler SJ
短期靶向治疗有可能预防秋季哮喘的恶化，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)奥马珠单抗与吸入皮质类固醇(ICS)助推剂在返校前4至6周开始使用时，跌倒恶化的发生率。一项三组随机、双盲、双安慰剂对照的多中心临床试验在市中心6至17岁的哮喘儿童中进行，这些儿童最近有一次或更多的哮喘发作(Clincaltrials.gov#NCT01430403)。在4至9个月的磨合阶段和4个月的干预阶段，继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中鼻病毒的干扰素-α反应的影响。在2012年和2013年秋季之前，727名儿童参加了调查，513名儿童被随机抽取，478名儿童进行了分析。与安慰剂组相比，奥马珠单抗组的跌倒恶化发生率显著降低(11.3%比21.0%；优势比[OR]，0.48；%CI，0.25-0.92)，但奥马珠单抗和ICS Boost组没有显著差异(8.4%比11.1%；OR，0.73；95%CI，0.33-1.64)。在预先指定的亚组分析中，在磨合期病情恶化的参与者中，奥马珠单抗显著优于安慰剂(6.4%比36.3%；OR，0.12；95%CI，0.02-0.64)和ICS Boost(2.0%比27.8%；OR，0.05；95%CI，0.002-0.98)。奥马利单抗可改善干扰素-α对鼻病毒的应答，在奥马利单抗组中，干扰素-α的增加与较少的病情恶化有关(OR，0.14；95%CI，0.01-0.88)。不良事件很少见，而且在军队中类似。在市中心的年轻人中，在返校前将奥马珠单抗加入正在进行的基于指南的护理中，可以减少秋季哮喘的恶化，特别是在那些最近病情恶化的人中。
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; % CI, 0.25–.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.