屋尘螨舌下过敏原免疫治疗在成人过敏性哮喘的疗效：一项随机临床试验
2016/07/07
摘要
重要性：屋尘螨(HDM)舌下过敏原免疫治疗(SLIT)是HDM过敏相关性哮喘的一种新的治疗选择。
目的：评估HDM SLIT vs安慰剂在吸入糖皮质激素（ICS）减量期间对哮喘急性加重的防治疗效和不良反应。
设计、设定 和参与者：这项双盲、随机、安慰剂对照试验于2011年8月至2013年4月在109个欧洲研究中心进行。受试者包括834名成年患者，他们经ICS或其联合制剂治疗仍然控制不佳，且伴有HDM相关性过敏性鼻炎。以及患有HDM过敏性鼻炎的成年患者。主要排除标准FEV1小于70%或在随机前3个月内有因哮喘而住院。评估疗效时间选择在研究最后的6个月，前三个月ICS减少50%以及之后三个月ICS完全撤退。
干预措施：在ICS和短效β2-激动剂沙丁胺醇基础上，受试者按1:1:1随机分配到三组，每日一次的安慰剂治疗方案（n=277）或HDM SLIT（剂量组：6 SQ-HDM [N = 275 ]或12 SQ-HDM [N = 282 ]）。
主要的结果和测量：主要终点：ICS减量期间开始到首次中、重度哮喘急性加重发作的时间。次要终点是哮喘症状的恶化、过敏原特异性免疫球蛋白G4（IgG4）的改变、哮喘控制或哮喘生活质量问卷的变化和不良反应。
结果：834名随机患者（平均年龄：33岁[范围：17-83岁]；女性：48%），693名完成了研究。与安慰剂组相比，6 SQ-HDM和12 SQ-HDM剂量组均显著降低了中度或重度哮喘急性发作的风险（对6 SQ-HDM组：风险比[HR]：0.72 [95% CI：0.52-0.99]，P = 0.045；对12 SQ-HDM组：HR：0.69 [95% CI：0.50-0.96]，P = 0.03）。基于实测数据（全分析数据集）的绝对风险差异在治疗组与安慰剂组分别为：6SQ-HDM组0.09（95% CI：0.01-0.15）和12 SQ-HDM组0.10（95% CI：0.02-0.16），两治疗组间无显著差异。与安慰剂相比，治疗组的哮喘症状的恶化风险降低（6 SQ-HDM组 HR: 0.72 [95% CI：0.49-1.02]，P =0.11；12 SQ-HDM组 HR: 0.64 [95% CI，0.42-0.96]，P = 0.03），且过敏原特异性IgG4显著增加。然而，各组在或ACQ、哮喘生活质量问卷的改变没有显著差异。研究期间未出现严重的全身性过敏反应的报告。最常见的不良反应为轻至中度口腔瘙痒（6 SQ-HDM组13%，12 SQ-HDM组20%和安慰剂组3%）、口腔水肿和咽喉发炎。
结论与关联：经ICS或其联合制剂治疗仍然控制不佳且伴有HDM相关性过敏性鼻炎的成人患者，增加用于维持治疗的HDM SLIT能延长ICS减量期间出现第一次中度或重度哮喘发作时间，估计在6个月绝对减少9至10个百分点；这种减少主要考虑与中度发作减少有关。两治疗组均出现治疗相关的不良反应。长期的有效性和安全性尚需要进一步的研究。
试验注册：clinicaltrialsregister.eu
（南方医科大学南方医院 彭显如 赵海金）
JAMA. 2016 Apr 26;315(16):1715-25.
Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma: ARandomized Clinical Trial.
Virchow JC1, Backer V2, Kuna P3, Prieto L4, Nolte H5, Villesen HH6, Ljørring C6, Riis B6, de Blay F7.
Virchow JC1, Backer V2, Kuna P3, Prieto L4, Nolte H5, Villesen HH6, Ljørring C6, Riis B6, de Blay F7.
JAMA. 2016 Apr 26;315(16):1715-25.
Abstract
IMPORTANCE:The housedustmite (HDM) sublingual allergenimmunotherapy (SLIT) tablet is a potential novel treatment option for HDM allergy-related asthma.
OBJECTIVES:To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticosteroid (ICS) reduction period.
DESIGN, SETTINGS, AND PARTICIPANTS:Double-blind, randomized, placebo-controlled trial conducted between August 2011 and April 2013 in 109 European trial sites. The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products, and with HDM allergy-related rhinitis. Key exclusion criteria were FEV1 less than 70% of predicted value or hospitalization due to asthma within 3 months before randomization. Efficacy was assessed during the last 6 months of the trial when ICS was reduced by 50% for 3 months and then completely withdrawn for 3 months.
INTERVENTIONS:1:1:1 randomization to once-daily treatment with placebo (n = 277) or HDM SLIT tablet (dosage groups: 6 SQ-HDM [n = 275] or 12 SQ-HDM [n = 282]) in addition to ICS and the short-acting β2-agonist salbutamol.
MAIN OUTCOMES AND MEASURES:Primary outcome was time to first moderate or severe asthma exacerbation during the ICS reduction period. Secondary outcomes were deterioration in asthma symptoms, change in allergen-specific immunoglobulin G4 (IgG4), change in asthma control orasthma quality-of-life questionnaires, and adverse events.
RESULTS:Among 834 randomized patients (mean age, 33 years [range, 17-83]; women, 48%), 693 completed the study. The 6 SQ-HDM and 12 SQ-HDM doses both significantly reduced the risk of a moderate or severe asthma exacerbation compared with placebo (hazard ratio [HR]: 0.72 [95% CI, 0.52-0.99] for the 6 SQ-HDM group, P = .045, and 0.69 [95% CI, 0.50-0.96] for the 12 SQ-HDM group, P = .03). The absolute risk differences based on the observed data (full analysis set) in the active groups vs the placebo group were 0.09 (95% CI, 0.01-0.15) for the 6 SQ-HDM group and 0.10 (95% CI, 0.02-0.16) for the 12 SQ-HDM group. There was no significant difference between the 2 active groups. Compared with placebo, there was a reduced risk of an exacerbation with deterioration in asthma symptoms (HR, 0.72 [95% CI, 0.49-1.02] for the 6 SQ-HDM group, P = .11, and 0.64 [95% CI, 0.42-0.96] for the 12 SQ-HDM group, P = .03) and a significant increase in allergen-specific IgG4. However, there was no significant difference for change in asthma control questionnaire or asthma quality-of-life questionnaire for either dose. There were no reports of severe systemic allergic reactions. The most frequent adverse events were mild to moderate oral pruritus (13% for the 6 SQ-HDM group, 20% for the 12 SQ-HDM group, and 3% for the placebo group), mouth edema, and throat irritation.
CONCLUSIONS AND RELEVANCE:Among adults with HDM allergy-related asthma not well controlled by ICS, the addition of HDM SLIT to maintenance medications improved time to first moderate or severe asthma exacerbation during ICS reduction, with an estimated absolute reduction at 6 months of 9 to 10 percentage points; the reduction was primarily due to an effect on moderate exacerbations. Treatment-related adverse events were common at both active doses. Further studies are needed to assess long-term efficacy and safety.
TRIAL REGISTRATION:clinicaltrialsregister.eu Identifier: 2010-018621-19.
上一篇：
母乳喂养婴儿早期引入致敏食物（Allergenic Foods）可以预防1-3岁食物过敏？-一项大样本随机对照试验
下一篇：
Dupilumab治疗中到大剂量吸入糖皮质激素加长效β2受体激动剂仍未能控制持续性哮喘成年患者的疗效和安全性:一项随机双
