桦树花粉过敏中安慰剂注射与无注射队列的临床结局：一项探索性跨研究比较

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中文摘要

背景/目的： 安慰剂反应可能使过敏原免疫治疗（AIT）试验的解读复杂化，因为基于症状和药物的结局除治疗特异性效应外，还可能受到试验背景的影响。在传统双盲、安慰剂对照AIT试验中，无注射对照队列很少可得。因此，我们对两个安慰剂注射队列和一个无注射队列的桦树花粉过敏参与者的临床结局进行了探索性事后跨研究比较。方法：汇集来自三项评估甘露聚糖偶联桦树花粉类变应原EP-088-T502-T502-SIT-020、T502-SIT-045和T502-SIT-068的前瞻性临床研究的数据用于本跨研究比较。将研究T502-SIT-020和T502-SIT-045的安慰剂注射队列与研究T502-SIT-068的无注射队列进行比较。临床结局包括联合症状与药物评分（CSMS）、每日症状评分（dSS）和每日药物评分（dMS）。结果：主要峰值期分析分别纳入来自T502-SIT-020、T502-SIT-045和T502-SIT-068的60、93和160名参与者。在研究中心特异性的14天桦树花粉峰值期，无注射队列的CSMS中位数为2.14，而T502-SIT-020和T502-SIT-045安慰剂注射队列分别为1.34和1.07。这些数值描述性地对应于相对于无注射队列分别约低37%和50%的队列中位数。在三项源研究中定义一致的dSS中位数在无注射队列为1.22，而两个安慰剂注射队列分别为0.78和0.70。dMS中位数分别为0.93与0.39和0.36。在次要的固定4月1日至30日分析中观察到相同的队列间模式。结论：两个安慰剂注射队列均显示出低于无注射队列的CSMS和dSS值。由于这些队列非同期且来自不同研究，所观察到的差异不能确立安慰剂注射的因果效应。

英文摘要

Background/Objectives: Placebo responses can complicate the interpretation of allergen immunotherapy (AIT) trials because symptom- and medication-based outcomes may be influenced by the trial context in addition to treatment-specific effects. Injection-free comparison cohorts are rarely available in conventional double-blind, placebo-controlled AIT trials. We therefore conducted an exploratory post hoc cross-study comparison of clinical outcomes in two placebo-injection cohorts and an injection-free cohort of birch pollen-allergic participants. Methods: Data from three prospective clinical studies evaluating the mannan-conjugated birch pollen allergoid EP-088-T502-T502-SIT-020, T502-SIT-045, and T502-SIT-068-were assembled for this cross-study comparison. Placebo-injection cohorts from studies T502-SIT-020 and T502-SIT-045 were compared with the injection-free cohort from study T502-SIT-068. Clinical outcomes included the Combined Symptom and Medication Score (CSMS), daily Symptom Score (dSS), and daily Medication Score (dMS). Results: The primary peak-period analysis included 60, 93, and 160 participants from T502-SIT-020, T502-SIT-045, and T502-SIT-068, respectively. During the site-specific 14-day peak birch pollen periods, median CSMS was 2.14 in the injection-free cohort compared with 1.34 and 1.07 in the T502-SIT-020 and T502-SIT-045 placebo-injection cohorts, respectively. These values corresponded descriptively to approximately 37% and 50% lower cohort medians, respectively, relative to the injection-free cohort. Median dSS, which was defined consistently across the three source studies, was 1.22 in the injection-free cohort compared with 0.78 and 0.70 in the two placebo-injection cohorts. Median dMS was 0.93 compared with 0.39 and 0.36, respectively. The same between-cohort pattern was observed in the secondary fixed 1-30 April analysis. Conclusions: Both placebo-injection cohorts showed lower CSMS and dSS values than the injection-free cohort. Because the cohorts were non-concurrent and derived from separate studies, the observed differences do not establish a causal effect of placebo injections.