Ellis Anne K, Murrieta-Aguttes Margarita, Furey Sandy, Picard Pascaline, Carlsten Christopher
Division of Allergy and Immunology, Dept of Medicine, Queen's University, Kingston, ON, Canada.
Sanofi Consumer Health Care, Gentilly, France.
ERJ Open Res. 2021 Apr 6;7(2). doi: 10.1183/23120541.00806-2020. eCollection 2021 Apr.
In recent decades, seasonal allergic rhinitis (SAR) prevalence has increased and recent studies have shown that air pollutants, such as diesel exhaust particles (DEP), can increase inflammatory and allergic biomarkers. The aim of this study was to investigate the effects of DEP on SAR symptoms induced by ragweed and to evaluate the efficacy and safety of fexofenadine HCl 180 mg placebo. This phase 3, single-centre, sequential, parallel-group, double-blind, randomised study (NCT03664882) was conducted in an environmental exposure unit (EEU) during sequential exposures: Period 1 (ragweed pollen alone), Period 2 (ragweed pollen+DEP), and Period 3 (ragweed pollen+DEP+single-dose fexofenadine HCl 180 mg or placebo). Efficacy and safety were evaluated in Period 3. Primary endpoints were the area under the curve (AUC) of total nasal symptom score (TNSS) from baseline to hour 12 (AUC) during Period 1 and Period 2; and the AUC of the TNSS from hour 2 to 12 (AUC) during Period 3. 251 out of 257 evaluable subjects were included in the modified intent-to-treat population. Least squares mean difference (95% CI) for TNSS Log AUC in Period 2 Period 1 was 0.13 (0.081-0.182; p<0.0001). Least squares mean difference in TNSS Log AUC for fexofenadine HCl placebo during Period 3 was -0.24 (-0.425--0.047; p=0.0148). One fexofenadine HCl-related adverse event was observed. SAR symptoms evoked by ragweed were aggravated by DEP. Fexofenadine HCl 180 mg was effective in relieving pollen-induced, air pollution-aggravated allergic rhinitis symptoms.
近几十年来，季节性过敏性鼻炎（SAR）的患病率有所上升，最近的研究表明，空气污染物，如柴油尾气颗粒（DEP），可增加炎症和过敏生物标志物。本研究的目的是调查DEP对豚草诱发的SAR症状的影响，并评估180毫克盐酸非索非那定与安慰剂的疗效和安全性。这项3期、单中心、序贯、平行组、双盲、随机研究（NCT03664882）在一个环境暴露单元（EEU）中进行，采用序贯暴露：第1阶段（仅豚草花粉）、第2阶段（豚草花粉+DEP）和第3阶段（豚草花粉+DEP+单剂量180毫克盐酸非索非那定或安慰剂）。在第3阶段评估疗效和安全性。主要终点是第1阶段和第2阶段从基线到第12小时的总鼻症状评分（TNSS）曲线下面积（AUC）；以及第3阶段从第2小时到第12小时的TNSS的AUC。257名可评估受试者中的251名被纳入改良意向性治疗人群。第2阶段与第1阶段相比，TNSS对数AUC的最小二乘均值差异（95%CI）为0.13（0.081-0.182；p<0.0001）。第3阶段盐酸非索非那定与安慰剂相比，TNSS对数AUC的最小二乘均值差异为-0.24（-0.425--0.047；p=0.0148）。观察到1例与盐酸非索非那定相关的不良事件。DEP会加重豚草诱发的SAR症状。180毫克盐酸非索非那定可有效缓解花粉诱发的、空气污染加重的过敏性鼻炎症状。
