Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma.

ABSTRACT

BACKGROUND: Dupilumab, an anti-IL-4 receptor α mAb, inhibits IL-4/IL-13 signaling, key drivers of type 2/TH2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting ß2-agonists. OBJECTIVE: To examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR). METHODS: A post hoc analysis reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w) doses under investigation in phase 3 (NCT02414854) was carried out. PAR was defined at study entry as a specific response to typical perennial antigens (IgE ≥0.35 Ku/L). RESULTS: Overall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT-22 total score (least squares mean difference, -5.98; 95% CI, -10.45 to -1.51; P = .009) and all 4 AR-associated symptoms evaluated (nasal blockage, -0.60; 95% CI, -0.96 to -0.25; runny nose, -0.67; 95% CI, -1.04 to -0.31; sneezing, -0.55; 95% CI, -0.89 to -0.21; postnasal discharge, -0.49; 95% CI, -0.83 to -0.16; all P < .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant, decreases in SNOT-22 total score (-1.82; 95% CI, -6.46 to 2.83; P = .443 vs placebo) and in each AR-associated symptom. In patients without PAR, no differences were observed for these measures versus placebo. CONCLUSIONS: Dupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.