Department Campus Charité Mitte, Universitätsmedizin Berlin, Berlin, Germany.
Allergy Therapeutics, Worthing, UK.
Allergy. 2018 Sep;73(9):1812-1822. doi: 10.1111/all.13478. Epub 2018 Jun 19.
The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose.
The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction in Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modeling analysis was used to test for the dose response, shape of the curve and estimation of the median effective dose (ED ), a measure of potency.
Statistically significant dose responses (P < .01 & .001) were seen, respectively. The highest cumulative dose in PQBirch204 (27 300 standardized units [SU]) approached a plateau. Potency of the PQBirch was demonstrated by an ED 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups.
Increasing the cumulative dose of PQBirch 5.5-fold from 5100 to 27 300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase in efficacy of 50%, without compromising safety. The cumulative dose response was confirmed to be curvilinear in shape.
白桦过敏原、酪氨酸吸附物、单磷酰脂质 A（POLLINEX Quattro Plus 1.0 毫升白桦 100%）是一种有效且耐受性良好的短期皮下免疫治疗药物。我们进行了两项 2 期研究，以确定其最佳累积剂量。
这些研究在德国、奥地利和波兰进行（EudraCT 编号：2012-004336-28 PQBirch203 和 2015-000984-15 PQBirch204），使用了广泛的累积剂量。在两项研究中，受试者在花粉季节外每周接受 6 次治疗注射。在筛查、基线和完成治疗后 3-4 周进行结膜激发试验，以量化每个累积剂量下总症状评分（作为主要终点）的降低。使用多重比较程序和模型分析来测试剂量反应、曲线形状和中位有效剂量（ED）的估计值，ED 是效力的衡量标准。
分别观察到具有统计学意义的剂量反应（P <.01 和.001）。PQBirch204 中的最高累积剂量（27 300 标准化单位 [SU]）接近平台。PQBirch 的效力通过 ED 2723 SU 得到证明，略高于当前剂量的一半。活性剂量的治疗出现不良事件的发生率相似，大多数不良事件是短暂的和轻度的。所有组的依从性均超过 85%。
将 PQBirch 的累积剂量从 5100 增加到 27 300 SU，增加了 5.5 倍，与安慰剂相比，绝对差异为 1.91，相对差异为 32.3%，疗效提高了 50%，而不影响安全性。累积剂量反应被确认为曲线形状。
