Dupilumab Effect on Exacerbations and Lung Function Despite Withdrawal of Inhaled Corticosteroids/long-Acting Beta Agonists

Abstract

Background Dupilumab reduces severe exacerbations, improves lung function in patients with moderate-to-severe asthma, and demonstrates an acceptable safety profile. Reduction of inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) dose is recommended in patients who respond to biologics, but little evidence is available regarding the safety of such reduction. This analysis evaluated the impact of ICS/LABA withdrawal on exacerbations and lung function in patients with asthma and baseline eosinophils >=300 cells/muL in 2 clinical studies (Phase 2a NCT01312961] and Phase 2 NCT03387852]). Method Patients (>=18 years) received dupilumab 300 mg weekly (Phase 2a) or dupilumab 300 mg every 2 weeks (Phase 2) for 12 weeks or placebo. LABA was discontinued at Week 4, and ICS tapered over Weeks 6 to 9. Adjusted annualized exacerbation rates, changes from baseline to Week 12 and from Week 4 to 12 in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1), and proportions of patients who maintained 5-item Asthma Control Questionnaire (ACQ- 5) scores ), and proportions of patients who maintained 5-item Asthma Control Questionnaire (ACQ- 5) scores 1 significantly improved from baseline to Week 12 in both studies. No further improvements in pre-BD FEV1 were observed from Week 4 (after LABA discontinuation) to Week 12 (table 1). By Week 12, 62.0/61.3% (dupilumab) and 38.3/36.6% (placebo) of patients in Phase2a/Phase 2 studies were able to withdraw ICS while maintaining asthma control (ACQ-5 <1.5). Conclusion Dupilumab reduced exacerbations and significantly improved lung function despite ICS/LABA withdrawal in patients with moderate-to-severe asthma. (Table Presented).