Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial.

Importance: Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases.

Objective: To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis.

Design, Setting, And Participants: A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up.

Targeting key proximal drivers of type 2 inflammation in disease.

Systemic type 2 inflammation encompassing T helper 2 (TH2)-type responses is emerging as a unifying feature of both classically defined allergic diseases, such as asthma, and a range of other inflammatory diseases. Rather than reducing inflammation with broad-acting immunosuppressants or narrowly targeting downstream products of the TH2 pathway, such as immunoglobulin E (IgE), efforts to target the key proximal type 2 cytokines - interleukin-4 (IL-4), IL-5 and IL-13 - represent a promising strategy to achieve therapeutic benefit across multiple diseases. After several initial disappointing clinical results with therapies targeting IL-4, IL-5 or IL-13 in asthma, applying a personalized approach achieved therapeutic benefit in an asthma subtype exhibiting an 'allergic' phenotype.