背景:在慢性自发性荨麻疹(CSU)中,白细胞介素(IL)-4和IL-13可能通过IL-4受体的表达直接促进肥大细胞的活化,或间接通过上调免疫球蛋白E(IgE)的产生。Dupilumab在3期随机,显着改善CSU体征和症状,安慰剂对照LIBERTY-CSUCUPID研究A.本分析探讨了dupilumab对LIBERTY-CSUCUPID研究A患者的CSU体征和症状以及血清IgE水平的影响,其中血清总IgE在基线时高于和低于100IU/mL。
方法:H1-抗组胺难治性CSU患者接受dupilumab(n=70)或安慰剂(n=68)治疗24周。疗效终点为血清总IgE水平从基线到第12周和第24周的变化,超过7天的瘙痒严重程度评分(ISS7),荨麻疹活动评分超过7天(UAS7),在基线时血清总IgE高于和低于100IU/mL的dupilumb或安慰剂治疗的患者中,HSS7天以上的Hives严重程度评分(HSS7)。
结果:Dupilumab治疗在第12周[dupilumab:-31.9%(-41.9;-22.6);安慰剂:-6.3%(-21.3;14.9)]和第24周[dupilumab:-48.2%(-56.8;-39.5);安慰剂:-6.3%(-34.5;14.8)无论基线IgE水平如何,在dupilumab治疗的患者中观察到类似的IgE相对于基线的降低。Dupilumab治疗在12和24周内改善了ISS7,UAS7和HSS7,无论基线血清IgE水平如何(通过亚组比较,所有治疗的相互作用p≥0.59),在IgE水平变化与ISS7,UAS7和HSS7结局之间观察到弱相关性(r<0.2)。
结论:Dupilumab显著改善CSU体征和症状,降低血清IgE,无论基线IgE水平如何。在目前的分析中,在CSU中,基线总IgE作为dupilumab治疗应答生物标志物没有预测价值.IgE下调,肥大细胞活化和组胺释放的关键介质,可能至少部分解释了dupilumab在减少CSU体征和症状方面的有效性.
背景:ClinicalTrials.gov标识符:NCT04180488。
BACKGROUND: In chronic spontaneous urticaria (CSU), interleukin (IL)-4 and IL-13 may promote mast cell activation directly via IL-4 receptor expression, or indirectly via upregulated immunoglobulin E (
IgE) production. Dupilumab significantly improved CSU signs and symptoms in the phase 3, randomized, placebo-controlled LIBERTY-CSU CUPID Study A. This analysis explores the impact of dupilumab on CSU signs and symptoms and serum
IgE levels in patients from LIBERTY-CSU CUPID Study A with serum total
IgE above and below 100 IU/mL at baseline.
METHODS: Patients with H1-antihistamine-refractory CSU received dupilumab (n = 70) or placebo (n = 68) for 24 weeks. Efficacy endpoints were change from baseline to weeks 12 and 24 in serum total IgE levels, Itch Severity Score over 7 days (ISS7), Urticaria Activity Score over 7 days (UAS7), and Hives Severity Score over 7 days (HSS7) in dupilumab- or placebo-treated patients with serum total IgE above and below 100 IU/mL at baseline.
RESULTS: Dupilumab treatment significantly reduced median (interquartile range) IgE levels at week 12 [dupilumab: -31.9% (-41.9; -22.6); placebo: -6.3% (-21.3; 14.9)] and week 24 [dupilumab: -48.2% (-56.8; - 39.5); placebo: - 6.3% (-34.5; 14.8)]. Similar IgE reductions relative to baseline were observed in dupilumab-treated patients regardless of baseline
IgE level. Dupilumab treatment improved ISS7, UAS7, and HSS7 over 12 and 24 weeks, regardless of baseline serum IgE level (interaction p ≥ 0.59 for all treatment by subgroup comparisons), with weak correlations (r < 0.2) observed between IgE level changes and ISS7, UAS7, and HSS7 outcomes.
CONCLUSIONS: Dupilumab significantly improved CSU signs and symptoms and reduced serum IgE, regardless of baseline
IgE levels. In the current analysis, baseline total IgE had no predictive value as a dupilumab treatment response biomarker in CSU. Downregulation of IgE, a key mediator of mast cell activation and histamine release, may at least partially explain the effectiveness of dupilumab in reducing CSU signs and symptoms.
BACKGROUND: ClinicalTrials.gov Identifier: NCT04180488.