Long-term effectiveness and safety of dupilumab in severe asthma: a 5-year real-life multicenter observational cohort study

Dupilumab is a monoclonal anti-IL-4Rα antibody for severe asthma (SA). An early access program (EAP) allowed 64 patients facing therapeutic dead end to be initiated in late 2017 (Dupin et al, Clin Exp Allergy 2020). We conducted an observational multicenter (n=13) retrospective real-life cohort study to assess effectiveness and tolerance of dupilumab 5 years after treatment initiation. 47 (73%) patients of the EAP still on treatment after 12 months were included in the cohort. Investigators collected annual data until M60. At M60, 35 patients (75%) were still being treated with dupilumab. Treatment was discontinued because of poor asthma control (n=7), patient’s preference (n=2), asymptomatic hypereosinophilia (n=1), memory loss (n=1), missing information (n=1). At M60 vs M0, asthma remained controlled (ACT score 20 [16-24] vs 14 [8-17]), annual exacerbation rate had decreased (0 [0-2] vs 5 [3-10]), and median pre-BD FEV1 increased (66% [48-87] vs 59 [46-76]). 17/21 of oral corticosteroids dependent patients at M12 were weaned at M60. 13 patients had been weaned between M0 and M12. Of 15 patients with nasal polyps, only 1 had required re-operation at M60. 12 patients complained of anosmia at M0, none at M60. Eosinophilia remained noteworthy at M60 with 9 patients (53%) with Eos>500/mm3, 1 patient (6%) with Eos>1500/mm3. Median eosinophilia was 540 [220-870] vs 200 [90-370] at M0. No organ complications were reported in any patient. Dupilumab remains effective and well tolerated 5 years after initiation in a real life setting. Switch rate is low. A small number of patients maintain a hypereosinophilia after 5 years, which justifies continued monitoring.