Center for Rhinology and Allergology, Wiesbaden, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Allergy. 2016 Jul;71(7):967-76. doi: 10.1111/all.12860. Epub 2016 Mar 29.
The safety and tolerability of a mite allergoid subcutaneous allergen immunotherapy (SCIT) product was previously established. The aim of this study (EudraCT number: 2011-000393-61) was to find the optimally safe and effective allergoid dose by evaluating several dosages in patients with house dust mite (HDM)-induced allergic rhinoconjunctivitis (ARC) using a titrated nasal provocation test (TNPT).
In total, 290 adult ARC patients (148 females; 142 males) with established HDM allergy and with a positive TNPT were randomized to receive placebo or mite allergoid SCIT 6667, 20 000, 50 000 or 100 000 AUeq/ml for 12 months. Patients were updosed weekly, followed by monthly maintenance dosing. The primary study endpoint comprised the clinical response to TNPT after 12 months of treatment. Secondary endpoints included response to TNPT after 6 months, PNIF measurements, symptom and medication scores during the last 8 weeks of treatment, serum immunoglobulins and safety assessments.
After 12 months, a dose-response was observed showing statistically significant improvements in the TNPT with SCIT concentrations of ≥20 000 AUeq/ml, while no significantly different outcomes were reached after 6 months. Specific serum IgG and IgG4 levels were dose dependently increased. In the highest dose group, more treatment-emergent adverse events were observed compared with the lower dose groups.
In this mite allergoid SCIT dose finding study in HDM-induced ARC, concentrations of ≥20 000 AUeq/ml showed both immunological effects and clinical efficacy in the TNPT compared with placebo. The risk-benefit ratio favours 20 000 AUeq/ml and 50 000 AUeq/ml strengths for further clinical development.
先前已经确定了一种螨变应原皮下变应原免疫治疗（SCIT）产品的安全性和耐受性。本研究（EudraCT 编号：2011-000393-61）的目的是通过评估几种剂量在屋尘螨（HDM）诱导的变应性鼻炎结膜炎（ARC）患者中的作用，找到最安全有效的螨变应原剂量，使用滴定鼻激发试验（TNPT）。
共有 290 名成年 ARC 患者（148 名女性；142 名男性）接受了 HDM 过敏确立和 TNPT 阳性的治疗，他们被随机分配接受安慰剂或螨变应原 SCIT 6667、20000、50000 或 100000 AUeq/ml，治疗 12 个月。患者每周进行增量给药，随后每月进行维持剂量给药。主要研究终点包括治疗 12 个月后 TNPT 的临床反应。次要终点包括 6 个月后的 TNPT 反应、PNIF 测量、治疗最后 8 周的症状和药物评分、血清免疫球蛋白和安全性评估。
12 个月后，观察到剂量反应，表明 SCIT 浓度≥20000 AUeq/ml 与 TNPT 有统计学显著改善，而 6 个月后则未达到显著不同的结果。特异性血清 IgG 和 IgG4 水平呈剂量依赖性增加。在最高剂量组中，与低剂量组相比，观察到更多的治疗中出现的不良事件。
在这项 HDM 诱导的 ARC 中进行的螨变应原 SCIT 剂量发现研究中，与安慰剂相比，浓度≥20000 AUeq/ml 的 SCIT 在 TNPT 中显示出免疫效果和临床疗效。风险效益比有利于进一步临床开发 20000 AUeq/ml 和 50000 AUeq/ml 两种浓度。
