Real-World Experience of Dupilumab for the Treatment of Severe Asthma in the United Kingdom: a retrospective study

Abstract

Introduction Dupilumab binds to the alpha subunit of the interleukin (IL)-4 receptor (IL-4Ra), inhibiting both IL-4 and IL-13, key and central drivers of type 2 inflammation. In the QUEST phase 3 clinical trial, treatment of patients with uncontrolled moderate-to-severe asthma with dupilumab resulted in reduced rates of severe asthma exacerbations, improved lung function, and improved asthma control. DUPIAZA (NCT06064526), a retrospective observational realworld evidence study, is the first real-world, multi-site study of dupilumab treatment for severe asthma in the UK. Methods 144 dupilumab-treated patients across 9 tertiary centers were assessed for patient demographics and clinical characteristics, safety, and efficacy. Recruited patients had either failed to respond to or were ineligible for other biologics. Data reported are from the pre-first biologic baseline, predupilumab baseline, 12 months post-dupilumab initiation, and last recorded visit. Results Comparing 12 months post-dupilumab to pre-dupilumab baseline, overall, patients experienced a 69% reduction in severe exacerbations (rate ratio: 0.31; P<0.0001), a 260-mL improvement in forced expiratory volume in 1 second (mean ratio: 1.14; P<0.06), a 0.80-point improvement in 6-item Asthma Control Questionnaire score (mean ratio: 0.76; P<0.002) and a 0.74-point improvement in Mini Asthma Quality of Life Questionnaire score (mean ratio: 1.23; P<0.26). At baseline, in patients dependent on oral corticosteroids (OCS), there was a 44% reduction in maintenance OCS (mean ratio: 0.56; P<0.0001), whilst also achieving a 58% reduction in severe exacerbations (rate ratio: 0.42; P<0.0001). In non-OCS dependent patients, at baseline, there was an 87% reduction in exacerbations (mean ratio: 0.13; P<0.0001). Additionally, in the overall population, 36 patients (25%) met Delphi-defined super-responder criteria. Safety was consistent with the known adverse event profile of dupilumab from previous studies. Conclusion In a real-world severe asthma population in the UK, dupilumab treatment led to a significant reduction in exacerbations and the need for maintenance OCS, as well as improvements in symptomatic asthma control and asthmarelated quality of life. Notably, these positive outcomes were observed in patients with a high disease burden, not responding to other biologics or were ineligible for them, thereby highlighting the importance of treatment formularies to include biologics that target multiple pathways, including IL- 4Ra signaling.