Subjects with physician-diagnosed aspirin-exacerbated respiratory disease (AERD) who remain unacceptably symptomatic with a SNOT 22 score > 18 despite routine medical therapy will be enrolled in this single center, single-blinded study assessing the efficacy of dupilumab in AERD.

This is a single blind, placebo controlled trial to be conducted in adult patients with AERD to determine the efficacy and safety of dupilumab in treating symptoms of chronic rhinosinusitis.

All subjects will be treated with the FDA-approved and the commercially available dose for adult atopic dermatitis of 300 mg every 2 weeks administered subcutaneously, based on the observed efficacy and safety of this dose. In addition to atopic dermatitis, this dose has also been shown to be efficacious in adult asthma.15 Patients will not be treated with a loading dose since other studies of dupilumab in asthma and chronic rhinosinusitis with nasal polyposis have not used a loading dose.

There will be a one month screening period to determine the patient's eligibility and establish symptom control and baseline parameters.

Patients will continue their background medications for chronic rhinosinusitis with nasal polyposis and asthma. These medications may include nasal corticosteroids, nasal antihistamines, systemic antihistamines, leukotriene receptor antagonists, 5 lipo-oxygenase inhibitors, inhaled corticosteroids, long-acting beta agonists, and long acting muscarinic antagonists. These controller medications will not be dispensed or supplied by the sponsor.

Inclusion Criteria:

1. Patients 18 years and older with a physician diagnosis of aspirin-exacerbated respiratory disease, as defined by a physician diagnosis of asthma, chronic rhinosinusitis with nasal polyposis, and a convincing clinical history of NSAID sensitivity
2. All subjects must have a SNOT 22 score ≥ 19 despite standard medical therapy. This minimal SNOT 22 was calculated by taking the range of SNOT 22 scores in studies of normal controls plus 8.9, which is the minimal clinically meaningful improvement in SNOT 22 score detected by patients.
3. Able to understand and willingness to sign informed consent
4. Able to comply with study procedures

Exclusion Criteria:

1. Patient < 18 years of age
2. Pregnancy or breast feeding
3. Current tobacco use
4. Significant, uncontrolled medical conditions
5. Ongoing malignancy or history of malignancy in remission within the past 12 months
6. Current treatment with immunosuppressive medications except chronic oral steroids
7. Currently increasing dose of aeroallergen immunotherapy (patients on stable dose of aeroallergen immunotherapy will be allowed to participate)
8. Treatment with omalizumab, reslizumab, mepolizumab within 4 months of enrollment