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

Rationale: 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. Dupilumab blocks the shared receptor component for IL-4/IL-13, key and central drivers of type 2 inflammation, improves lung function, reduces the rate of severe exacerbations in patients (≥ 12 years) with moderate-to-severe asthma for up to 3 years, and demonstrates an acceptable safety profile. 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 (NCT03387852).

Methods: Patients (≥ 18 years) using ICS and LABA were randomized to receive 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.

Results: 31 patients received dupilumab and 41 placebo. Dupilumab vs placebo significantly reduced severe exacerbation rates over the treatment by 74.7% (P=0.015) and ACQ-5 scores at Week 12 from baseline (mean [SD]:−1.18 [0.79] vs−0.70 [0.87]; P=0.0493). Furthermore, FeNO levels decreased significantly at Week 12 from baseline in dupilumab vs placebo (median [Q1–Q3]:−7.0 [−9.0 to−1.0] ppb vs 2.0 [−5.0 to 23.0] ppb; P=0.0085), and these decreases were sustained.

Conclusion: 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 without ICS or LABA background therapy for at least 3 weeks.

Publikationsverlauf

Artikel online veröffentlicht:
18. März 2025