Dupilumab Reduces Asthma Disease Burden and Recurrent SCS Use in Patients with CRSwNP and Coexisting Asthma

Abstract

Purpose: Dupilumab significantly reduced the requirement for systemic corticosteroids (SCS) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with CRSwNP and coexisting asthma typically have a higher disease burden and have more difficulty in managing disease. Here, we report an analysis of asthma outcomes and SCS use in patients with CRSwNP and coexisting asthma. Patients and Methods: This was a post hoc analysis of the randomized, placebo-controlled SINUS-24 and SINUS-52 studies (NCT02912468/NCT02898454) in patients with severe CRSwNP and coexisting asthma (patient self-reported) from the pooled intention-to-treat population randomized to dupilumab 300 mg every 2 weeks or placebo. On-treatment SCS use was estimated using Kaplan–Meier analysis. Forced expiratory volume in 1 s (FEV1), percent predicted FEV1, and the 6-item Asthma Control Questionnaire (ACQ-6) were assessed at baseline and Week 24 (pooled SINUS-24/52) in patients with/without history of asthma exacerbation or prior SCS use. Results: Of 337 patients with coexisting asthma, 88 (26%) required on-treatment SCS use. The requirement for on-treatment SCS use for any reason was significantly lower with dupilumab (20/167 patients; 12%) vs placebo (68/170; 40%); hazard ratio (95% confidence interval) 0.248 (0.150–0.409); p < 0.0001. The most frequent reasons for SCS use were nasal polyps (dupilumab 3% and placebo 27%) and asthma (2% and 9%, respectively). FEV1, percent predicted FEV1, and ACQ-6 were all significantly improved at Week 24 with dupilumab vs placebo irrespective of history of asthma exacerbation or prior SCS use (all p < 0.01). Conclusion: Dupilumab significantly reduced the requirement for SCS and improved asthma outcomes irrespective of history of asthma exacerbation or prior SCS use vs placebo in patients with CRSwNP and coexisting asthma, demonstrating concomitant reduction of SCS use and asthma disease burden in these patients. Plain Language Summary: Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are type 2 inflammatory conditions that often coexist. Patients with both CRSwNP and asthma generally have worse symptoms that are more difficult to treat. Their standard treatment is topical (inhaled/intranasal) corticosteroids, but where this is ineffective, systemic corticosteroids, also called SCS, are used. SCS are effective at reducing nasal polyp size and improving symptoms, but this effect often does not last, and many patients experience side effects when SCS are used for a long time. Dupilumab, a drug that targets type 2 inflammation, is approved for treating both uncontrolled CRSwNP and moderate-to-severe asthma. Here, we investigate whether dupilumab changes how often patients with CRSwNP and asthma need to use SCS and its effect on their asthma. We found that dupilumab-treated patients were 75% less likely to need SCS than patients treated with placebo and also had significantly greater improvements in measures of their asthma severity, irrespective of their history of previous asthma attacks or previous SCS use. These results show that, in patients with CRSwNP and asthma, dupilumab can improve asthma symptoms and reduce the need for SCS use. Using fewer SCS may help patients avoid the side effects associated with SCS use.