Abstract Context In pediatrics, access to biologic therapies targeting type 2 inflammation remains limited by age and indication restrictions within marketing authorizations (MA). Real-world data on off-label use are lacking. We aimed to describe national prescribing practices, efficacy, and safety of anti-Th2 biologics used outside MA recommendations in French pediatric pulmonology and allergy centers. Methods We conducted a retrospective, observational, multicenter study including children (0-18 yrs) treated off-label between 2005 and 2025 with omalizumab, dupilumab, mepolizumab, or tezepelumab. Data were collected through a standardized anonymized form across seven tertiary hospitals affiliated with the RespiRare® network and the French Society of Allergy. The primary endpoint was characterization of off-label prescribing circumstances (indication, rationale, and regulatory framework). Secondary endpoints were clinical efficacy and safety. Results Eighty-eight children were included (omalizumab = 78 89%, dupilumab = 8 9%, mepolizumab = 1, tezepelumab = 1). Off-label prescriptions involved food allergy (35), severe asthma (32), vernal keratoconjunctivitis (10), allergic bronchopulmonary aspergillosis in cystic fibrosis (6), chronic urticaria (3), nasal polyposis (1), and macrophage activation syndrome (1). Sixty percent concerned diseases without any pediatric MA in France; 40% did not meet eligibility criteria (mainly age 6 years or IgE/eosinophil levels outside authorized ranges). All prescribers justified off-label use by lack of therapeutic alternatives (59% inefficacy or intolerance to standard care; 41% absence of approved therapy). Prescriptions were validated in multidisciplinary meetings (local 53%, national 34%). Adverse events occurred in 14% of omalizumab-treated patients (mainly mild injection-site pain, fatigue, headache); three discontinued treatment. No serious events were reported with other biologics. Among asthmatic children (n = 32), severe exacerbations decreased from a median 3 2-8 to 0 0-1.2 per year (p 0.0001), with significant improvement in AQLQ (1.7→6.1; p 0.0001) and c-ACT scores (12→22; p = 0.003). In food-allergic children, the tolerated milk protein dose rose from 16.5 g to 255 g (p = 0.002), with smaller skin-prick diameters. Conclusions This first French nationwide cohort documents real-world off-label use of Th2-targeted biologics in children with severe or rare respiratory/allergic disorders. Off-label prescribing was medically driven, well-tolerated, and associated with meaningful clinical improvement. These findings support the development of prospective registries and may inform future pediatric MA extensions and personalized treatment strategies in severe pediatric asthma and allergic diseases. This abstract is funded by: No
Josserand et al. (Fri,) studied this question.