Severe Asthma Exacerbations Controlled with Dupilumab in Patients With Comorbid Chronic Rhinosinusitis and/or Nasal Polyposis

By Jenny Powers

PARIS -- September 19, 2018 -- Dupilumab consistently reduced the rate of severe exacerbations in moderate to severe asthma and showed comparative efficacy in patients with and without comorbid chronic rhinosinusitis or nasal polyposis (CRS/NP), according to a post hoc analysis of the phase 3 Liberty Asthma QUEST trial presented here at the 2018 International Congress of the European Respiratory Society (ERS).

Dupilumab 200 mg significantly reduced the relative risk of severe asthma exacerbation over a 52-week period compared with placebo in patients with CRS/NP, patients without CRS/NP, and the overall intent-to-treat (ITT) population (all P< .0001).

At 300 mg, dupilumab significantly reduced the relative risk of severe asthma exacerbation over 52 weeks compared with placebo in patients with CRS/NP (P< .0002), patients without CRS/NP (P< .0002), and the ITT cohort (all P< .0001).

“Both chronic rhinosinusitis and nasal polyposis are characterised by a type 2 inflammatory reaction; asthma patients with chronic rhinosinusitis with or without nasal polyps tend to show poorer asthma control than patients without comorbidities,” explained Ian Pavord, MD, Oxford Respiratory Biomedical Research Centre, Oxford, United Kingdom, on September 16. “Typically, the more severe the CRS, the more severe the asthma.”

The phase 3 Liberty Asthma QUEST trial enrolled 1,902 patients who were randomised 2:2:1:1 to dupilumab 300 or 200 mg administered subcutaneously or to dual placebo administered at 2 or 1.14 mL. The study duration was 52 weeks.

Dr. Pavord and colleagues assessed the efficacy of dupilumab in a subgroup of 382 patients with comorbid chronic rhinosinusitis with or without nasal polyposis compared with patients without comorbid CRS/NP. The dupilumab 200-mg cohort included 126 patients with CRS/NP and the placebo group included 63 patients. In the non-CRS/NP cohort, 505 patients received dupilumab 200 mg and 254 received placebo.

The dupilumab 300-mg cohort included 123 and 70 patients with CRS/NP on dupilumab and placebo, respectively, versus 510 and 251 patients without CRS/NP in the respective treatment groups.

“At baseline, the patients with CRS/NP had a higher number of severe exacerbations within the past year than patients without CRS/NP,” Dr. Pavord pointed out.

The change from baseline in forced expiratory volume (FEV1) was nearly doubled with dupilumab 200 and 300 mg compared with placebo as early as the second week of treatment in patients with CRS/NP, at 0.3 L least squares mean compared with 0.05 L with both placebo doses, respectively. Non-CRS/NP patients showed similar FEV1 results.

The change from baseline to week 12 with dupilumab 200 mg versus placebo was 0.200 L (P = .0034) in patients with CRS/NP, 0.110 L (P< .0001) in patients without CRS/NP, and 0.125 L (P< .0001) in the ITT population. With dupilumab 300 mg, the respective cohorts showed an FEV1 change of 0.150 L (P = .0092), 0.125 L (P< .0001), and 0.140 L (P< .0001).

“Dupilumab was generally well tolerated in the ITT population,” Dr. Pavord noted.

Serious adverse events occurred in <8.5% of the ITT population, and injection-site reactions were the most commonly occurring adverse event.

“Consistent with greater disease severity, asthma patients with CRS/NP had a significantly greater severe exacerbation history than patients without CRS/NP,” Dr. Pavord concluded.

Funding for this study was provided by Sanofi, Paris, France, and Regeneron, Tarrytown, New York.

[Presentation title:Dupilumab Efficacy in Asthma Patients With Comorbid Chronic Rhinosinusitis or Nasal Polyposis in Liberty Asthma QUEST. Abstract OA1651]
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