Prevalence of Allergy and Type 2 Inflammatory Comorbidities in Adolescents With Uncontrolled, Moderate-to-Severe Asthma

Background: Asthma prevalence in adolescents has increased in recent years yet remains under studied. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2-mediated inflammation in multiple diseases. In the phase 3, LIBERTY ASTHMA QUEST study (NCT02414854), add-on dupilumab 200mg or 300mg every 2 weeks vs matched placebo reduced annualized rates of severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients aged ≥12 years with uncontrolled, moderate-to-severe asthma. Similar efficacy was observed between adults and adolescents and in subgroups of patients with evidence of allergic asthma or type 2 comorbidities, such as allergic rhinitis and chronic rhinosinusitis with nasal polyps. This post hoc analysis compared the proportions of adolescent and adult patients enrolled in the LIBERTY ASTHMA QUEST study who met allergic criteria or had type 2 inflammatory comorbid disease. Methods: Adolescent (aged ≥12 to 17 years) and adult (aged ≥18 years) patients were eligible for enrollment in the study. The proportions of adolescents and adults meeting allergic criteria per the most commonly used criteria in clinical practice in the USA (≥1 perennial aeroallergen-specific IgE ≥0.35 IU/mL and total IgE ≥30 IU/mL), or with history of type 2 inflammatory comorbid disease (atopic dermatitis, allergic conjunctivitis, allergic rhinitis, chronic rhinosinusitis, nasal polyposis, eosinophilic esophagitis, food allergy, or hives) were assessed. Results: Overall, 81% of adolescent patients in the combined dupilumab 200mg/300mg groups and 87% of adolescent patients in the combined placebo groups met allergic criteria, compared with 56% and 55% of adult patients, respectively (Table). Similarly, proportions of patients with history of type 2 inflammatory comorbidities were much higher in the adolescent subgroups (dupilumab: 93%; placebo: 97%) compared with the adult groups (dupilumab: 78%; placebo: 79%). The most frequently observed perennial aeroallergen-specific IgE ≥ 0.35 IU/mL were seen in higher proportions of adolescent patients than adult patients: Aspergillus fumigatus (adolescents: 79–87% across groups vs adults: 55–56%); Alternaria tenuis/alternata (81–87% vs 55–56%); cat dander (76–87% vs 55%); Cladosporium herbarum/hormodendrum (72–82% vs 49–50%); German cockroach (72–82% vs 49–50%); and dog dander (76–87% vs 55%). Conclusion: In the LIBERTY ASTHMA QUEST study, dupilumab improved asthma symptoms and lung function in patients with uncontrolled asthma. Although a comparably small number of adolescents were enrolled in the study (n=107), a higher proportion of adolescents met allergic criteria or had history of type 2 inflammatory comorbidities compared with adults.