DUPILUMAB Anti-IL-4R alpha monoclonal antibody Treatment of atopic dermatitis Treatment of asthma

摘要

The cytokines interleukin-4 (IL-4) and IL-13 are associated with type 2 helper T-cell (Th2) immunity and are known to play roles in allergic disease. The ability to block IL-4 and IL-13 downstream signaling at the same time is possible as the cytokines signal through different but overlapping receptors which each contain an a subunit of the IL-4 receptor. To this end, the human monoclonal antibody dupilumab was synthesized. Dupilumab has been found to antagonize IL-4 and IL-13 signaling in vitro and to reduce levels of chemokines associated with atopy and IgE in patients with atopic dermatitis and asthma. The monoclonal antibody has demonstrated acceptable safety and has been associated with improvements in pruritus, disease severity scores and quality of life in patients with atopic dermatitis and improvements in lung function and asthma control in individuals with asthma. Dupilumab has progressed to phase III development for both these indications, and the results of a proof-of-concept study have encouraged further clinical development for treating patients with chronic sinusitis with nasal polyps.