2025/10/29 by Stéphanie Wanin, Rola Abou Taam, Lisa Giovannini Chami +10 · 1 voice
Medicine · Immunology and Microbiology · #Asthma and respiratory diseases #Dermatology and Skin Diseases #IL-33, ST2, and ILC Pathways
paper · pdf · doi:10.1111/all.70119
openalex publication_date 2025/10/29 · openalex created_date 2025/10/30 · openalex updated_date 2026/07/22
In France, the prevalence of asthma in children is 9%–10% [1], with 2%–10% of those having severe asthma [2]. Severe asthma in adolescents (age 12–18 years) is characterized by the precocity and accumulation of sensitizations and allergic comorbidities [3]. The French COBRAPed severe asthma cohort reported allergy in 85% of the patients, with high healthcare resource utilization and impaired quality of life [4]. Biologics have revolutionized the management of severe asthma [2], and accurate phenotyping of severe asthma, through assessment of allergic status and eosinophil counts, for example, enables more personalized treatment [5]. Dupilumab is a human monoclonal antibody that blocks the shared receptor component for interleukins 4/13, key and central drivers of type 2 inflammation in multiple diseases [6]. It is approved in the European Union for patients aged ≥ 12 years with severe asthma associated with type 2 inflammation and in children aged ≥ 6 years with asthma inadequately controlled with other treatments. However, the characteristics of children who benefit from dupilumab in the real world are not well understood. PEDIASTHMA (NCT05070663) is a 52-week, multicenter, observational, prospective, retrospective, real-world study conducted at 15 sites across metropolitan France. Adolescents (age 12–17 years) who were already treated with or started dupilumab treatment for severe uncontrolled asthma were eligible to enroll (severe asthma in children is defined as asthma that remains uncontrolled despite optimized treatment with high-dose inhaled corticosteroids [ICS]-long-acting beta-agonists [LABA] or requires high-dose ICS-LABA to prevent it from becoming uncontrolled) [7]. After a protocol amendment (October 27, 2022), children (age 6–11 years) were also included in the study. The primary objective of PEDIASTHMA is to describe the characteristics of enrolled children and adolescents, including demographic and disease characteristics, quality of life, medical and asthma history, and treatments for asthma at initiation of dupilumab (including previous treatment with other biologics). This pre-specified interim analysis of PEDIASTHMA describes the characteristics (as defined in the primary endpoint) of the first 50 adolescents (age 12–17 years) enrolled. All data are descriptive and presented as mean (standard deviation [SD]). Detailed information on study background, design, ethical considerations, inclusion and exclusion criteria, secondary endpoints, statistical analysis, and investigators can be found in Appendices I–III, Table S1, and Figure S1. At enrollment, 66% (n = 33) of patients were male (Table 1). They were 3.9 (3.9) years old at the diagnosis of severe asthma based on the clinical expertise of the investigator and 14.7 (1.7) years at the first administration of dupilumab. They had 3.2 (2.9) severe exacerbations in the year before enrollment and spent 1.3 (3.4) days in an intensive care unit due to exacerbations since their diagnosis of severe asthma. Fifty-eight percent (29/50) of patients were sensitized to ≥ 2 aeroallergens, and almost two-thirds (64%) had ≥ 1 coexisting type 2 inflammatory condition (Figure 1A). Almost a third of the patients had regular passive exposure to tobacco smoke, but only 1 patient reported active tobacco consumption (Table S2). Patients presented with impaired lung function, with a pre-bronchodilator forced expiratory volume in 1 s (FEV1) z-score of −1.43 (1.61); a pre-bronchodilator FEV1/FVC (forced vital capacity) z-score of −0.52 (2.48); and elevated type 2 inflammatory biomarkers, including a blood eosinophil count of 442.0 (332.9) cells/μL (Table 1). In all, 27 (54%) of the enrolled patients had previously been treated with biologic therapy for asthma, with 7 (26%) of these having received more than 1 biologic (Figure 1B). Half (24/50) of enrolled patients reported previous use of conventional inhaler therapy at the initiation of dupilumab (data not reported for all patients; Table 1). This interim analysis of the first 50 patients who initiated dupilumab in a real-world setting in France reveals disease characteristics and prior treatments in adolescents with severe asthma. Over half of these patients were previously treated with another biologic, illustrating a potential unmet need for effective treatments in this population. The adolescents in the PEDIASTHMA registry had similar demographics and baseline disease characteristics to the adolescents in the QUEST phase 3 clinical trial (aged 12–17 years; similar sex, body mass index, age, age at diagnosis, and lung function), though the PEDIASTHMA population had slightly higher mean (SD) number of severe exacerbations in the previous year, 3.2 (2.9) compared with 1.91 (1.56) in QUEST, and PEDIASTHMA adolescents also had a slightly higher eosinophil and immunoglobulin E (IgE) levels [7]. With regard to comorbidities, more patients in QUEST had comorbid allergic rhinitis, while more in PEDIASTHMA had comorbid atopic dermatitis, food allergy, and allergic conjunctivitis [8]. While some age-related and geographical characteristics vary between PEDIASTHMA (France) and the adolescent and adult asthma registries, such as ProVENT [9] (Germany, Austria, and Switzerland) and RAPID [10] (global), disease characteristics are relatively similar. Adolescents enrolled in PEDIASTHMA had a mean (SD) pre-bronchodilator percent predicted FEV1 of 82.9 (19.3), while participants in the ProVENT and RAPID registries had 70.81 (23.67) and 70.3 (20.3), respectively. Total blood eosinophil and FeNO levels were comparable between adolescents in PEDIASTHMA and patients in the other registries; however, the total IgE levels were over four-fold higher in adolescents in the PEDIASTHMA registry. The ongoing follow-up of this cohort will provide valuable insights into the real-world effectiveness of dupilumab in adolescents with severe asthma and an understanding of the characteristics of patients who have benefited from switching biologics. Christele Da Silva, Jérôme Msihid, Olivier Ledanois, Rebecca Gall, Harry J. Sacks, Juby A. Jacob-Nara, and Capucine Daridon contributed to the study concept and design; Stéphanie Wanin, Rola Abou Taam, Lisa Giovannini Chami, Christophe Marguet, Jocelyne Just, and Antoine Deschildre contributed to data collection and data interpretation. All authors contributed to the writing of this manuscript and had full access to all the data. All authors participated in the interpretation of the data, provided critical feedback, and took responsibility for the accuracy, completeness, and protocol adherence of the data and analyses; all authors gave final approval of this version to be published. Medical writing/editorial assistance was provided by Lola MacRae, PhD, and Ayse Gurpinar, PhD, of Excerpta Medica, and was funded by Sanofi and Regeneron Pharmaceuticals Inc., according to the Good Publication Practice guidelines. S.W.: Aimmune, ALK, AstraZeneca, GSK, Novartis, Sanofi, Stallergenes—personal fees. R.A.T.: ALK, AstraZeneca, GSK, Novartis, Sanofi, Stallergenes—speaker/consulting fees. L.G.C.: ALK, AstraZeneca, Novartis, Sanofi, Stallergènes—speaker/consulting fees. C.M.: ALK, GSK, Novartis, Sanofi—speaker/consulting fees. J.J.: ALK-Abello, AstraZeneca, GSK, Novartis, Sanofi, Stallergènes, Zambon—speaker/consulting fees. C.D.S., J.M., O.L., J.A.J.-N., C.D.: Sanofi—employees, may hold stock and/or stock options in the company. R.G.: Regeneron Pharmaceuticals Inc.—employee and shareholder. H.J.S.: Regeneron Pharmaceuticals Inc.—employee; Optinose—shareholder. A.D.: Aimmune Therapeutics, ALK, AstraZeneca, Celltrion, DBV Technologies, GSK, Novartis, Regeneron Pharmaceuticals Inc., Sanofi, Stallergenes Greer, Viatris–speaker/consulting fees. Qualified researchers may request access to patient-level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient-level data will be anonymized, and study documents will be redacted to protect the privacy of our trial participants. Further details on Sanofi's data-sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org/. Table S1: PEDIASTHMA registry investigators. Table S2: Tobacco exposure (passive and active) of adolescents participating in PEDIASTHMA. Figure S1: PEDIASTHMA study design (NCT05070663). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.