Effectiveness and Safety of Dupilumab in Patients with Chronic Rhinosinusitis with Nasal Polyps and Associated T2 Comorbidities: One-Year Real Life Round

<b>Background/Objectives:</b> Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a common and debilitating inflammatory disorder primarily driven by type 2 immune mechanisms. Its frequent overlap with asthma, allergic rhinoconjunctivitis and atopic dermatitis highlights the need for therapeutic strategies able to address multimorbidity within the same pathogenic spectrum. The development of monoclonal antibodies targeting signaling pathways provides an effective and well-tolerated option that addresses common comorbidities. Targeting the IL-4 receptor alpha subunit, dupilumab is a completely human IgG4 monoclonal antibody that reduces type 2 inflammation in many organ systems by blocking IL-4 and IL-13 signaling. This study aimed to assess the long-term effectiveness and safety of dupilumab in a real-world cohort of patients with severe CRSwNP, stratified according to the presence of common type 2 comorbidities, over a 52-week treatment period. <b>Methods:</b> We conducted a prospective, multicenter, observational study across ten Italian secondary care centers for Allergy and Clinical Immunology and Otolaryngology. All participating centers were affiliated with the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). Enrolled adult subjects with severe CRSwNP received dupilumab treatment in the context of standard care for 52 weeks. Several efficacy parameters were used. <b>Results:</b> A significant improvement was detected for all the applied efficacy parameters, i.e., 22-item Sinonasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the first second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI), Atopic Dermatitis Control Toll (ADCT) and Dermatology Life Quality Index (DLQI) scores for AD. Dupilumab was well-tolerated, with no new safety signals. <b>Conclusions:</b> This multicenter real-world study demonstrates that dupilumab provides sustained, clinically meaningful, and safe benefits for patients with severe CRSwNP and coexisting type 2 comorbidities, supporting its role as an integrated therapeutic option in precision management of type 2 inflammatory diseases.