Table_2_Characterization of disease flares and impact of mepolizumab in patients with hypereosinophilic syndrome.docx

In patients with hypereosinophilic syndrome (HES), mepolizumab reduces the incidence of HES-related clinical signs and symptoms (flares). However, reports characterizing flare manifestations are limited. The double-blind, parallel-group 200622 trial (NCT02836496) enrolled patients ≥12 years old with HES for ≥6 months, ≥2 flares in the previous year, and screening blood eosinophil count ≥1000 cells/μL. Patients maintained ≥4 weeks stable HES therapy, before randomization (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. This post hoc analysis investigated flare manifestations and duration by re-examining the Core Assessments form and narrative recorded for each flare during the study. Flare symptoms were retrospectively categorized into constitutional, dermatological, respiratory, nasal, gastrointestinal, neurologic and other. The most frequently reported flare symptoms were constitutional (94% of flares), dermatological (82% of flares) and respiratory (72% of flares); flares reported in patients receiving mepolizumab compared with placebo were generally similar in terms of the frequency of symptoms reported. Mepolizumab was associated with a shorter median (range) duration of flares (10.0 [4, 126] days) versus placebo (26.0 [1, 154] days). In patients with HES, flares were associated with symptoms linked to multiple organ systems highlighting the challenges faced for treating flares.
Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02836496, identifier NCT02836496.

嗜酸性粒细胞增多综合征（hypereosinophilic syndrome）患者接受美泊利珠单抗 (mepolizumab) 治疗时，可降低与HES相关的临床体征与症状，即病情急性发作 (flares) 的发生率。然而，目前针对病情急性发作的临床表现特征的相关报道较为有限。
本项双盲平行组试验200622（临床试验编号NCT02836496）纳入了符合以下条件的HES患者：年龄≥12岁、确诊HES时长≥6个月、既往1年内出现≥2次病情急性发作，且筛查时外周血嗜酸性粒细胞计数≥1000个/μL。所有受试者在随机分组前需接受至少4周的稳定HES治疗；随后以1:1的比例随机分配至每4周皮下注射美泊利珠单抗（300mg）组或安慰剂组，两组均联合基线HES治疗，总干预时长为32周。
本项事后分析通过重新审查研究期间记录的每项病情急性发作的核心评估表及相关叙述性记录，对发作的临床表现特征与持续时长进行了分析。研究人员对发作症状进行了回顾性分类，分为全身症状、皮肤症状、呼吸道症状、鼻部症状、胃肠道症状、神经系统症状及其他类别。
报告频次最高的发作症状依次为全身症状（占所有发作事件的94%）、皮肤症状（82%）与呼吸道症状（72%）；与安慰剂组相比，美泊利珠单抗组患者报告的发作症状频率总体相似。美泊利珠单抗组患者的发作中位（范围）持续时间为10.0[4,126]天，显著短于安慰剂组的26.0[1,154]天。
在HES患者中，病情急性发作常伴随多器官系统相关症状，这凸显了发作治疗所面临的挑战。
临床试验注册：https://clinicaltrials.gov/ct2/show/NCT02836496，试验编号NCT02836496。