Background Hypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT). Objective To investigate whether genetic and type 2 (T2) inflammatory biomarkers correlate with disease severity in subjects with allergic asthma, and whether this can be modified by AIT. Methods MITRA ([NCT01433523][1]) was a phase III, randomised, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT)-tablets in adults with HDM allergic asthma. Post hoc analyses of the study population (N=742) evaluated associations between T2 inflammatory (blood eosinophils, eosinophil cationic protein (ECP), total IgE and tryptase) and genetic (single-nucleotide polymorphisms, SNP) biomarkers (n=582) for the primary study endpoint (time to first moderate/severe asthma exacerbation). SNP associations were verified in HDM-positive subgroup from an independent 3-year Severe Asthma Research Programme (SARP3) subject cohort. Results An increased asthma exacerbation risk in subjects homozygous for SNP rs7216389 (chromosomal locus 17q12-21) was reduced (p = 0.037) by treatment with HDM SLIT (HR=0.37 (95% CI 0.22 to 0.64), p<0.001). The associations between exacerbation risk and 17q12-21 SNPs were replicated in the SARP3 HDM-positive subgroup. High levels of T2 biomarkers were associated with increased risk of asthma exacerbations in the placebo group. HDM SLIT-tablet treatment reduced this risk (blood eosinophils: HR=0.50 (95% CI 0.30 to 0.85); ECP: HR=0.45 (95% CI 0.29 to 0.87); tryptase: HR=0.45 (95% CI 0.25 to 0.80)). The treatment effect was higher (p = 0.006) for subjects with a higher number of elevated T2 biomarkers. Conclusions HDM SLIT-tablet AIT is efficacious in HDM-sensitised asthma subjects with a genetic asthma predisposition and/or an underlying T2 endotype. Trial registration number [NCT01433523][1]. Data are available on reasonable request. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01433523&atom=%2Fthoraxjnl%2F79%2F4%2F332.atom

中文翻译：

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遗传和 T2 生物标志物与 HDM 舌下免疫治疗哮喘的疗效相关

背景 对屋尘螨 (HDM) 过敏原的过敏是过敏性哮喘症状的常见原因，可以通过过敏免疫疗法 (AIT) 有效治疗。目的 探讨遗传和 2 型 (T2) 炎症生物标志物是否与过敏性哮喘受试者的疾病严重程度相关，以及 AIT 是否可以改变这种关系。方法 MITRA ([NCT01433523][1]) 是一项针对 HDM 过敏性哮喘成人患者的 HDM 舌下免疫治疗 (SLIT) 片剂的 III 期、随机、双盲、安慰剂对照试验。对研究人群 (N=742) 的事后分析评估了 T2 炎症（血液嗜酸性粒细胞、嗜酸性粒细胞阳离子蛋白 (ECP)、总 IgE 和类胰蛋白酶）与遗传（单核苷酸多态性，SNP）生物标志物 (n=582) 之间的关联主要研究终点（第一次中度/重度哮喘恶化的时间）。SNP 关联在独立的 3 年严重哮喘研究计划 (SARP3) 受试者队列的 HDM 阳性亚组中得到验证。结果 通过 HDM SLIT 治疗，SNP rs7216389（染色体位点 17q12-21）纯合受试者的哮喘发作风险增加降低（p = 0.037）（HR=0.37（95% CI 0.22 至 0.64），p<0.001）。恶化风险与 17q12-21 SNP 之间的关联在 SARP3 HDM 阳性亚组中得到了复制。安慰剂组中高水平的 T2 生物标志物与哮喘恶化风险增加相关。HDM SLIT 片剂治疗降低了这种风险（血液嗜酸性粒细胞：HR=0.50（95% CI 0.30 至 0.85）；ECP：HR=0.45（95% CI 0.29 至 0.87）；类胰蛋白酶：HR=0.45（95% CI 0.25 至 0.80） ））。对于 T2 生物标志物升高数量较多的受试者，治疗效果较高 (p = 0.006)。结论 HDM SLIT 片剂 AIT 对具有遗传性哮喘易感性和/或潜在 T2 内型的 HDM 敏感哮喘受试者有效。试用注册号[NCT01433523][1]。可根据合理要求提供数据。[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01433523&atom=%2Fthoraxjnl%2F79%2F4%2F332.atom