MedicalResearch.com Interview with:
Prof. Claus Bachert
Prof Dr. Dr. h.c. Claus Bachert
Head Upper Airways Research Laboratory (URL)
Chief of Clinics ENT-Department
University Hospital Ghent
Medical Research: What is the background for this study? What are the main findings?
Prof. Bachert: Chronic sinusitis with nasal polyposis represents mucosal inflammation, and polyps in the nasal cavity and sinuses, which result in long-term symptoms of nasal obstruction and congestion, reduction in or loss of sense of smell, and loss of quality of life. Patients with nasal obstruction or congestion have a two-fold higher risk of sleep dysfunction, increased fatigue, and decreased work productivity. About 40 percent of chronic sinusitis with nasal polyps patients develop asthma, which often is non-allergic late-onset disease. Treatment options consist of nasal and systemic glucocorticosteroids; long-term or repeated treatment with oral GCS carries a great risk of side effects in these patients. Surgery of the sinuses is another option, but recurrence of polyps is frequent. Further treatment options are highly needed.
About 85% of nasal polyps represent a type 2 inflammation, with increased eosinophils and IgE formation. Dupilumab is an investigational therapy that inhibits signaling of IL-4 and IL-13, two key cytokines required for type 2 (Th2) immune responses. Dupilumab has been successfully administered in patients with asthma and atopic dermatitis.
The current randomized, double-blind, placebo-controlled group study enrolled 60 adult patients with chronic sinusitis with nasal polyposis refractory to intranasal corticosteroids at 13 sites in the United States and Europe. Following four weeks of mometasone furoate nasal spray (MFNS) run-in, patients in the study received 300 milligrams (mg) of dupilumab or placebo once per week subcutaneously for 16 weeks, after an initial loading dose of 600 mg. All patients in the study continued to receive daily MFNS. Eligible patients had bilateral nasal polyposis and showed chronic symptoms of sinusitis, despite treatment with an intranasal corticosteroid for at least two months. Fifty-eight percent of patients in the study had received prior nasal surgery for their condition.
We found that dupilumab treatment was associated with significant improvements in endoscopic, clinical, radiographic, and pharmacodynamic end points after 16 weeks.
Significant improvements in quality of life and in major symptoms, such as sense of smell, nasal congestion, and nocturnal awakenings,were reported. In those patients with asthma, also lung function and asthma control were significantly better with Dupilumab compared to placebo. Dupilumab was generally well tolerated, and no serious adverse events were considered to be related to dupilumab.