度普利尤单抗可抑制多种特应性、过敏性疾病的 2 型炎症生物标志物。

Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases.

机构信息

Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.

Sanofi, Bridgewater, NJ, USA.

出版信息

Clin Exp Allergy. 2021 Jul;51(7):915-931. doi: 10.1111/cea.13954. Epub 2021 Jun 26.

BACKGROUND

Type 2 inflammation is common in numerous atopic/allergic diseases and can be identified by elevated biomarker levels. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation.

OBJECTIVE

Assessment of dupilumab effect on type 2 inflammatory biomarkers in atopic dermatitis (AD), asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis (EoE).

METHODS

Data were extracted from three randomized placebo-controlled trials of dupilumab in AD (NCT02277743, N = 671; NCT02277769, N = 708; NCT02260986, N = 740); and one each in asthma (NCT02414854, N = 1902); CRSwNP (NCT02898454, N = 448); and EoE (NCT02379052, N = 47). Biomarkers assessed were serum thymus and activation-regulated chemokine (TARC), plasma eotaxin-3, serum total immunoglobulin E (IgE), serum periostin and blood eosinophil count.

RESULTS

Dupilumab versus placebo significantly suppressed most type 2 inflammatory biomarker levels across all studies/indications where data were assessed. Reductions in serum TARC, plasma eotaxin-3 and serum periostin occurred rapidly, whereas reductions in serum total IgE were more gradual. Across diseases, at the end of treatment, median percentage change from baseline in TARC levels ranged from -24.8% to -88.6% (placebo +2.6% to -53.6%); -38.2% to -51.5% (placebo +8.3% to -0.16%) in eotaxin-3; -24.8% to -76.7% (placebo +8.3% to -4.4%) in total IgE; and -13.6% to -41.1% (placebo +10.1% to -6.94%) in periostin levels. Blood eosinophil responses to dupilumab varied by disease, with minimal changes in AD in the SOLO studies (median percentage change from baseline to end of treatment: 0% [95% CI: -15.8, 0]); transient increases followed by decreases to below-baseline levels in asthma (-14.6% [-20.0, -7.7]) and CRSwNP (-29.4% [-40.0, -16.3]); and significant decreases in EoE (-50.0% [-50.0, -33.3]).

CONCLUSION AND CLINICAL RELEVANCE

Dupilumab reduced levels of type 2 biomarkers across clinical studies in patients with AD, asthma, CRSwNP and EoE.

背景

2 型炎症常见于多种特应性/过敏性疾病，可通过升高的生物标志物水平来识别。度普利尤单抗是一种完全人源化的单克隆抗体，可阻断白细胞介素-4 和白细胞介素-13 的共同受体成分，这是 2 型炎症的关键和主要驱动因素。

目的

评估度普利尤单抗对特应性皮炎（AD）、哮喘、伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）和嗜酸性食管炎（EoE）中 2 型炎症生物标志物的影响。

方法

从三项度普利尤单抗治疗 AD 的随机安慰剂对照试验（NCT02277743，N=671；NCT02277769，N=708；NCT02260986，N=740）和一项哮喘（NCT02414854，N=1902）、CRSwNP（NCT02898454，N=448）和 EoE（NCT02379052，N=47）中各提取数据。评估的生物标志物包括血清胸腺和激活调节趋化因子（TARC）、血浆嗜酸性粒细胞趋化因子-3、血清总免疫球蛋白 E（IgE）、血清骨膜蛋白和血液嗜酸性粒细胞计数。

结果

与安慰剂相比，度普利尤单抗在所有评估数据的研究/适应症中均显著抑制了大多数 2 型炎症生物标志物水平。血清 TARC、血浆嗜酸性粒细胞趋化因子-3 和血清骨膜蛋白的降低迅速发生，而血清总 IgE 的降低则较为缓慢。在各种疾病中，治疗结束时，TARC 水平从基线的中位数百分比变化范围为-24.8%至-88.6%（安慰剂+2.6%至-53.6%）；-38.2%至-51.5%（安慰剂+8.3%至-0.16%）在嗜酸性粒细胞趋化因子-3 中；-24.8%至-76.7%（安慰剂+8.3%至-4.4%）在总 IgE 中；和-13.6%至-41.1%（安慰剂+10.1%至-6.94%）在骨膜蛋白水平。度普利尤单抗对血液嗜酸性粒细胞的反应因疾病而异，在 SOLO 研究中 AD 的变化最小（从基线到治疗结束时的中位数百分比变化：0%[95%CI：-15.8，0]）；哮喘（-14.6%[-20.0，-7.7]）和 CRSwNP（-29.4%[-40.0，-16.3]）中短暂增加后下降至低于基线水平；EoE 中显著下降（-50.0%[-50.0，-33.3]）。