Dupilumab Reduces Exacerbations and FeNO Levels and Improves Asthma Control with Inhaled Corticosteroid Withdrawal: a Phase 2 Study

<bold>BACKGROUND:</bold> Inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) dose reduction is recommended in patients who respond to biologics, but little evidence exists on the safety of this tapering. <bold>AIMS/OBJECTIVES:</bold> This analysis assessed the impact of ICS-LABA withdrawal on exacerbations, asthma control, and FeNO in patients with moderate-to-severe asthma and baseline blood eosinophil count ≥300 cells/µL in a phase 2 clinical trial (<ext-link>NCT03387852</ext-link>). <bold>METHODS:</bold> Patients (≥18 years) using ICS and LABA were randomized to dupilumab 300 mg or placebo every 2 weeks (q2w). After randomization, patients were instructed to discontinue LABA at Week 4, and ICS was tapered over Weeks 6 to 9; no use of ICS or LABA was permitted from Weeks 9 to 12. This analysis assessed adjusted annualized severe exacerbation rates over the treatment period and change from baseline to Week 12 in asthma control (5-item Asthma Control Questionnaire [ACQ-5] score) and FeNO. <bold>RESULTS:</bold> 31 patients received dupilumab and 41 placebo. Dupilumab vs placebo significantly reduced severe exacerbation rates over the treatment by 74.7% (<italic>P</italic>=0.015) and ACQ-5 scores at Week 12 from baseline (<italic>P</italic>=0.0493). Furthermore, FeNO levels decreased significantly in dupilumab vs placebo (<italic>P</italic>=0.0085), and these decreases were sustained. Safety findings were consistent with the known dupilumab safety profile. <bold>CONCLUSION:</bold> Dupilumab significantly reduced severe exacerbation rates over the treatment period and sustainably improved asthma control and reduced FeNO levels in patients with moderate-to-severe asthma with blood eosinophil counts ≥300 cells/mL and without ICS or LABA background therapy for at least 3 weeks.