30 patients suffering from AERD will be included in this single-center, prospective, explorative study for treatment with dupilumab. Before study initiation, informed consent will be obtained from all subjects. All patients with AERD can be included according to inclusion- and exclusion criteria.~AERD patients who had already obtained a monoclonal antibody for the treatment of asthma or polyps will also be included if at least a wash out period of 5 half -lives or 3 months has passed. The first visit will be performed at screening (day 0, V1/before dupilumab therapy). Clinically significant abnormal laboratory values will be ruled out prior to the first dose.~All patients will be administered subcutaneous doses of dupilumab in a biweekly fashion.~For several reasons comparison with placebo will not be performed:~All patients included are in urgent need for an effective treatment.~The only currently available alternative treatment option is a functional endoscopic sinus surgery (FESS). Usually there is a high recurrence rate after surgery.~All included patients have a long medical history concerning AERD. The rate of a spontaneous improvement or resolution in this patient population is negligible.~Spirometry (peak-flow and FEV1) and an asthma control test will be performed prior to dupilumab therapy, after 1, 3 and 6 months. In addition, the sinonasal outcome test-22 and the total nasal endoscopic polyps score as well as nasal congestion score, disease severity (by visual analogue scale=VAS), total symptom score (TSS) will be performed at baseline, after 1,3 and 6 months. To further evaluate the polyp size, a nasal CT will be performed at screening visit. To evaluate the sense of smell we will perform UPSIT testing before and after 6 months dupilumab.~All patients will have routine laboratory testing (blood chemistry, hematology) before and after 6 months of therapy. Adverse events will be recorded at each visit. Biological activity will be evaluated based on peripheral blood eosinophil counts, serum total Immunoglobulin E (IgE) levels and measurement of eosinophilic cationic protein in patients' sera at baseline and after 6 months.~To assess local changes in the nose caused by dupilumab treatment, nasal secretions, nasal mucosa samples (nasal curette), nasal microbiome as well as nasal biopsies will be collected.~After the end of study, treatment will be continued in all patients with significant improvement in asthmatic symptoms, nasal symptoms as well as a reduction of polyps.~For patients who did not experience clinical improvement, dupilumab treatment will be discontinued after 6 months.
To test the efficacy of dupilumab in patients with AERD regarding the intolerance to salicylic acid after 6 months. This will be evaluated by oral drug provocation testing with low dose salicylic acid after 6 months of dupilumab treatment.~Hypothesis:~After 6 months of therapy, patients will tolerate aspirin dose levels as tested with different dosages (125mg, 250mg and 500 mg).