Chronic rhinosinusitis with nasal polyps: mechanistic insights from targeting IL-4 and IL-13 via IL-4Rα inhibition with dupilumab

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex immunological upper airway disease . CRSwNP, particularly in Caucasians, often has a more distinct T2 inflammatory endotype. IL-4 and IL-13 are key upstream cytokines that help establish and sustain T2 inflammation as well as strongly influencing tissue remodeling. They have a shared signaling receptor IL-4R alpha. An attractive and novel therapeutic approach is by way of blocking IL-4 and IL-13 simultaneously via inhibiting IL-4R alpha. Dupilumab is a murine derived fully human monoclonal inhibitory antibody directed against IL-4R alpha which thereby prevents IL-4/IL-13 cell signaling. Following successful Phase 3 studies dupilumab has become the first licensed biologic for treating CRSwNP. Areas covered: This review covers the essential immunology of CRSwNP in the context of IL-4 and IL-13 signaling via IL-4R alpha. The potential mechanisms by which therapeutic improvements occur with dupilumab are evaluated. IL-4, IL-13, dupilumab and rhinosinusitis were used as the search terms in PubMed and Google Scholar through to August 2020. Expert commentary: Dupilumab has the potential to transform the care for patients with CRSwNP. It is essential that further studies are conducted promptly to identify disease-specific biomarkers and clinical traits to guide clinicians on best patient selection thereby ensuring optimal dupilumab outcomes.