Dupilumab Improves Outcomes in Patients with Chronic Rhinosinusitis with Nasal Polyps and Coexisting Asthma Irrespective of Baseline Asthma Characteristics

Abstract

Purpose Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease frequently coexisting with other type 2 conditions including asthma and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD). Coexisting asthma leads to increased CRSwNP symptom burden. Dupilumab, a monoclonal antibody that blocks the shared receptor component for interleukin-4 and -13, demonstrated efficacy in adults with severe CRSwNP in the Phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies, including in patients with coexisting asthma/NSAID-ERD. However, the impact of different asthma characteristics on dupilumab treatment in this population is unknown. We report CRSwNP and asthma outcomes with dupilumab in patients with CRSwNP and coexisting asthma according to baseline asthma characteristics. Methods Change from baseline at Week 24 (pooled studies) and Week 52 (SINUS-52) in CRSwNP outcomes (nasal polyp score, nasal congestion, 22-item Sino-Nasal Outcome Test [SNOT-22], loss of smell score, University of Pennsylvania Smell Identification Test) and asthma outcomes (5-item Asthma Control Questionnaire [ACQ-5], pre-bronchodilator forced expiratory volume in 1 second [FEV 1 ]) were analyzed post hoc for placebo and dupilumab 300 mg every 2 weeks according to baseline blood eosinophils ≥150/≥300 cells/µL, ACQ-5 scores <1.5/≥1.5, and FEV 1 <80%. Results In the pooled studies, 428/724 patients (59.1%) had coexisting asthma, of which 181/428 (42.3%) had coexisting NSAID-ERD. Dupilumab significantly improved all CRSwNP and asthma outcomes vs placebo at Week 24 (P < 0.001) regardless of baseline eosinophil or ACQ-5 category, or FEV 1 <80%. Similar magnitude of improvement was seen at Week 52 (SINUS-52) and in patients with NSAID-ERD (pooled studies, Week 24). By Week 24, improvements with dupilumab exceeded the minimum clinically important differences for ACQ-5 and SNOT-22 in 35.2% to 74.2% and 72.0% to 78.7% of patients, respectively. Conclusion Dupilumab improved CRSwNP outcomes in patients with CRSwNP and coexisting asthma, and improved asthma outcomes, regardless of differences in baseline asthma characteristics.

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

“… 12 However, the results presented here suggest that dupilumab represents a viable therapeutic alternative for these difficult-to-treat patients with NP. Another recent analysis of the SINUS population demonstrated dupilumab efficacy in patients with CRSwNP and coexisting asthma irrespective of the severity of their asthma at baseline, 13 while the TRAVERSE study demonstrated dupilumab efficacy in patients with Global Initiative for Asthma (GINA)-defined type 2 asthma and CRSwNP. 14 The efficacy of dupilumab in CRSwNP and asthma may be explained by its mechanism of action in targeting IL-4 and IL-13, which are key drivers of type 2 inflammation in both diseases, 5 , 6 with more than 95% of the overall SINUS population having type 2 inflammatory disease on the basis of a range of biomarkers and clinical measures.…”

Asthma Phenotypes in the Era of Personalized Medicine

“…Clinical trials evaluating dupilumab's efficacy in asthma underscore a reduction in asthma exacerbation rates [14], attributed to substantial lung function enhancement and favorable tolerability, including glucocorticoid withdrawal [177,182,183]. Recent data showcasing dupilumab's positive impact on CRSwNP outcomes render it an effective choice for the concurrent treatment of Type 2 diseases [184]. Dupilumab's consistent effectiveness and safety span all age groups, extending even to pediatric patients [185][186][187][188].…”

Asthma Phenotypes in the Era of Personalized Medicine

“…Clinical trials of dupilumab for asthma demonstrated a reduction in asthmatic exacerbation rates [14], which can be attributed to a very significant improvement in lung function and favorable tolerability with glucocorticoid withdrawal [153,158,159]. Recent data demonstrating a positive effect of dupilumab on CRSwNP outcomes make this biological an effective option for treating patients with type 2 diseases concomitantly [160]. Due to its consistent efficacy and safety across all age groups, even in pediatric patients [161][162][163][164], this biologic has received the most approvals from regulatory agencies for use in pediatrics.…”