美泊利珠单抗治疗嗜酸性粒细胞增多综合征患者中，基线治疗与缓解发作的相关性。
Association Between Baseline Therapy and Flare Reduction in Mepolizumab-Treated Patients With Hypereosinophilic Syndrome.
机构信息
Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany.
Université de Lille, Centre Hospitalier Universitaire de Lille (CHU Lille), Institut d'Immunologie, Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Institute for Translational Research in Inflammation Infinite-U1286. Inserm, Lille, France.
出版信息
Front Immunol. 2022 Apr 13;13:840974. doi: 10.3389/fimmu.2022.840974. eCollection 2022.
BACKGROUND
Current standard-of-care treatments for hypereosinophilic syndrome (HES) include oral corticosteroids (OCS) and immunosuppressive/cytotoxic (IS/CT) therapies. The anti-IL-5 monoclonal antibody mepolizumab has also recently been approved for patients with this disease. The objective of this analysis was to assess the relationship between baseline therapy and flare reduction in patients with HES treated with mepolizumab, using data from the Phase III 200622 study (NCT02836496).
METHODS
In the double-blind, parallel-group 200622 study, eligible patients were ≥12 years old and had HES for ≥6 months, ≥2 flares in the previous 12 months, blood eosinophils ≥1000 cells/μL at screening and ≥4 weeks' stable HES therapy. Patients were randomised (1:1) to receive mepolizumab 300 mg subcutaneously or placebo every 4 weeks for 32 weeks plus their existing HES therapy. This , descriptive analysis assessed the effect of baseline HES therapy [IS/CT (± OCS), OCS No IS/CT, and No IS/CT/OCS] on the proportion of patients with ≥1 flare during the study period, the annualised rate of flares, time to first flare, and the proportion of patients with ≥1 flare during Weeks 20─32, with mepolizumab versus placebo.
RESULTS
Mepolizumab treatment was associated with a decrease in the proportion of patients who experienced ≥1 flare during the study period in all baseline therapy groups versus placebo (32-96% reduction). Similarly, the probability of a flare was lower with mepolizumab (14.3-31.4%) than placebo (35.7-74.1%) in all baseline therapy groups, as was the annualised flare rate (0.22-0.68 vs 1.14-1.62). The proportion of patients who experienced ≥1 flare during Weeks 20-32 was reduced with mepolizumab versus placebo for all baseline therapy groups (55-85% reduction). For all endpoints, the greatest effect of mepolizumab treatment was seen in the IS/CT (± OCS) group.
CONCLUSIONS
Patients with poorly controlled HES are likely to achieve clinical benefit with mepolizumab in terms of flare reduction, regardless of their baseline therapy.
CLINICAL TRIAL REGISTRATION
背景
嗜酸性粒细胞增多症（HES）的当前标准治疗方法包括口服皮质类固醇（OCS）和免疫抑制/细胞毒性（IS/CT）治疗。抗 IL-5 单克隆抗体美泊利珠单抗最近也已被批准用于治疗这种疾病的患者。本分析的目的是使用来自 III 期 200622 研究（NCT02836496）的数据评估 HES 患者接受美泊利珠单抗治疗时基线治疗与缓解的关系。
方法
在这项双盲、平行组 200622 研究中，符合条件的患者年龄≥12 岁，患有 HES 时间≥6 个月，在过去 12 个月中有≥2 次发作，筛选时血液嗜酸性粒细胞≥1000 个/μL，且接受 HES 治疗稳定≥4 周。患者被随机分配（1:1）接受美泊利珠单抗 300 mg 皮下注射或安慰剂，每 4 周一次，共 32 周，同时接受现有 HES 治疗。本描述性分析评估了基线 HES 治疗[IS/CT（±OCS）、OCS 无 IS/CT 和无 IS/CT/OCS]对研究期间≥1 次发作患者比例、发作年发生率、首次发作时间以及美泊利珠单抗与安慰剂相比在第 20─32 周期间≥1 次发作患者比例的影响。
结果
与安慰剂相比，在所有基线治疗组中，美泊利珠单抗治疗与研究期间≥1 次发作患者比例降低有关（32%-96%）。同样，在所有基线治疗组中，美泊利珠单抗的发作概率（14.3%-31.4%）低于安慰剂（35.7%-74.1%），发作年发生率也低于安慰剂（0.22-0.68 比 1.14-1.62）。与安慰剂相比，在所有基线治疗组中，美泊利珠单抗治疗在第 20-32 周期间≥1 次发作的患者比例降低（55%-85%）。对于所有终点，美泊利珠单抗治疗的最大效果见于 IS/CT（±OCS）组。
结论
无论基线治疗如何，控制不佳的 HES 患者使用美泊利珠单抗治疗可能会获得临床获益，从而降低发作。
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