Background

Anti–IL-5 therapy is a potential treatment for patients with hypereosinophilic syndrome (HES), although its clinical efficacy is unclear.

Objective

We sought to investigate the clinical efficacy and safety of mepolizumab versus placebo in patients with HES.

Methods

This randomized, multicenter, double-blind, placebo-controlled, phase III trial was conducted across 39 centers in 13 countries. Eligible patients had FIP1L1-PDGFRA-negative HES, experienced 2 or more flares (worsening of HES-related symptoms or blood eosinophil count requiring therapeutic escalation) in the previous 12 months, and had a screening blood eosinophil count greater than or equal to 1000 cells/μL. Patients were randomized (1:1) to subcutaneous mepolizumab (300 mg) or placebo every 4 weeks for 32 weeks, plus existing HES therapy. The primary outcome was the proportion of patients with 1 or more flares (worsening of HES-related symptoms necessitating therapy escalation or ≥2 courses of blinded rescue oral corticosteroids) during the study; in addition, patients who withdrew early from the study were counted as having a flare. Safety end points were also assessed.

Results

The proportion of patients experiencing 1 or more flares/withdrawing from the study was 50% lower with mepolizumab versus placebo (15 of 54 [28%] vs 30 of 54 [56%]; P = .002). Logistic regression analysis was consistent with the primary analysis (odds ratio, 0.28; 95% CI, 0.12-0.64; P = .003). Similar proportions of patients in the mepolizumab and placebo groups experienced on-treatment adverse events (48 of 54 [89%] vs 47 of 54 [87%]).

Conclusions

Compared with placebo, mepolizumab significantly reduced the occurrence of flares in patients with HES, with no new safety signals identified.

中文翻译：

---

美泊利单抗治疗嗜酸性粒细胞增多综合征的疗效和安全性：一项 III 期、随机、安慰剂对照试验。

背景

抗 IL-5 疗法是嗜酸性粒细胞增多综合征 (HES) 患者的一种潜在治疗方法，尽管其临床疗效尚不清楚。

客观的

我们试图调查美泊利单抗与安慰剂在 HES 患者中的临床疗效和安全性。

方法

这项随机、多中心、双盲、安慰剂对照的 III 期试验在 13 个国家的 39 个中心进行。符合条件的患者具有FIP1L1-PDGFRA-HES 阴性，在过去 12 个月内经历过 2 次或更多次发作（HES 相关症状恶化或需要治疗升级的血嗜酸性粒细胞计数），并且筛查血嗜酸性粒细胞计数大于或等于 1000 个细胞/μL。患者被随机分配 (1:1) 皮下注射美泊利单抗 (300 mg) 或安慰剂，每 4 周一次，持续 32 周，加上现有的 HES 疗法。主要结果是研究期间发生 1 次或多次发作（HES 相关症状恶化需要治疗升级或 ≥ 2 个疗程的盲法补救性口服皮质类固醇）的患者比例；此外，早期退出研究的患者被视为有突发事件。还评估了安全终点。

结果

与安慰剂组相比，美泊利单抗组经历 1 次或更多次发作/退出研究的患者比例低 50%（54 人中的 15 人 [28%] 对 54 人中的 30 人 [56%]；P = .002 ）  。逻辑回归分析与主要分析一致（比值比，0.28；95% CI，0.12-0.64；P  = .003）。在美泊利单抗组和安慰剂组中，相似比例的患者经历了治疗期间的不良事件（54 人中有 48 人 [89%] vs 54 人中有 47 人 [87%]）。

结论

与安慰剂相比，美泊利单抗显着降低了 HES 患者发作的发生率，且未发现新的安全信号。