Dupin Clairelyne, Belhadi Drifa, Guilleminault Laurent, Gamez Anne-Sophie, Berger Patrick, De Blay Frédéric, Bonniaud Philippe, Leroyer Christophe, Mahay Guillaume, Girodet Pierre-Olivier, Raherison Chantal, Fry Stéphanie, Le Bourdellès Geneviève, Proust Alain, Rosencher Lise, Garcia Gilles, Bourdin Arnaud, Chenivesse Cécile, Didier Alain, Couffignal Camille, Taillé Camille
Groupe Hospitalier Universitaire AP-HP Nord-Université de Paris, Hôpital Bichat, Service de Pneumologie et Centre de Référence constitutif des Maladies Pulmonaires Rares, Inserm UMR 1152, Paris, France.
Groupe Hospitalier Universitaire AP-HP Nord-Université de Paris, Hôpital Bichat, Département d'Epidémiologie, Biostatistiques et Recherche Clinique Unité de Recherche Clinique, Paris, France.
Clin Exp Allergy. 2020 Jul;50(7):789-798. doi: 10.1111/cea.13614. Epub 2020 May 29.
Dupilumab is a monoclonal anti-IL-4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side-effects and/or life-threatening exacerbations.
To assess changes in asthma control between baseline and 12 months of treatment.
Multi-centre (n = 13) retrospective real-life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447).
Overall, 64 patients with SA (median age 51, interquartile range [44-61]; 53% females) received dupilumab as add-on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7-16] to 22 [17-24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47-75] to 68% [58-88] (P = .001); and daily prednisone dose was reduced from 20 [10-30] to 5 [0-7] mg/d (P < .001). Annual exacerbations decreased from 4 [2-7] to 1 [0-2] (P < .001). Hypereosinophilia ≥1500/mm was observed at least once during follow-up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection-site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators.
CONCLUSION & CLINICAL RELEVANCE: In this first real-life cohort study of predominantly steroid-dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long-term prognosis of sustained dupilumab-induced hypereosinophilia.
度普利尤单抗是一种开发用于治疗重度哮喘（SA）的抗白细胞介素-4受体α单克隆抗体。在法国，针对经历不可接受的类固醇副作用和/或危及生命的病情加重的重度哮喘患者启动了度普利尤单抗早期准入计划。
评估治疗基线至12个月期间哮喘控制情况的变化。
多中心（n = 13）回顾性真实世界队列研究。本研究已在ClinicalTrials.gov注册（NCT04022447）。
总体而言，64例重度哮喘患者（中位年龄51岁，四分位间距[44 - 61]；53%为女性）接受度普利尤单抗作为最大标准治疗的附加疗法；76%的患者在基线时接受每日口服类固醇治疗。12个月后，哮喘控制测试中位评分从14[7 - 16]提高至22[17 - 24]（P < 0.001）；1秒用力呼气容积中位值从58%[47 - 75]增至68%[58 - 88]（P = 0.001）；每日泼尼松剂量从20[10 - 30]降至5[0 - 7]mg/d（P < 0.001）。年度病情加重次数从4[2 - 7]降至1[0 - 2]（P < 0.001）。16例患者（25%）在随访期间至少有一次观察到嗜酸性粒细胞增多≥1500/mm³，其中8例（14%）在6个月后仍持续存在。在研究期间，血液嗜酸性粒细胞计数增加并未改变临床反应。注射部位反应是最常见的副作用（14%）。观察到3例死亡，调查人员认为均与治疗无关。
在这项以类固醇依赖为主的重度哮喘患者的首次真实世界队列研究中，度普利尤单抗显著改善了哮喘控制和肺功能，减少了口服类固醇的使用和病情加重率。尽管由于回顾性研究存在局限性，但这些结果与对照试验的疗效数据一致。需要进一步研究来评估度普利尤单抗诱导的持续性嗜酸性粒细胞增多的临床意义和长期预后。
