Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a challenging condition that substantially impacts the quality of life of patients. The biologic drug, dupilumab, received Food and Drug Administration (FDA) approval in 2019 for treating CRSwNP when conventional therapy or surgery is ineffective. Real-world studies have demonstrated the promising results of dupilumab; however, additional data regarding its effectiveness and safety profile are required. We retrospectively gathered data on the effectiveness and safety of dupilumab in patients with CRSwNP a Saudi Arabian tertiary care setting, specifically focusing on patients that met the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020) criteria for biologic treatment. Methods: Focusing on the efficacy and safety of the medication, 22 adult patients diagnosed with CRSwNP and treated with dupilumab at Dr. Sulaiman Al Habib Hospitals between January 2020 and December 2023 were retrospectively analyzed based on post treatment improvement in: olfaction visual analogue scale (VAS) score, sinonasal outcome test 22 (SNOT22), eosinophil (ESO) count, total immunoglobin E (IgE) levels and total nasal polyp score (NPS). Results: Positive outcomes in terms of median improvement changes in various parameters such as olfaction (VAS) score from 10 to 0 , (SNOT22) from 45 to 15.5, (ESO) count from, total (IgE) levels from 134.7 to 19, and total (NPS) from 4 to 0 were identified. No participant required rescue interventions, the most common side effects were arthralgia and injection site erythema in a mean duration of follow up of 1. 8 years. Conclusion: Dupilumab is a safe and effective treatment for CRSwNP patients in Saudi Arabia, aligning with EPOS2020 criteria for biologic treatment. However, further research and follow-ups are necessary to confirm these initial findings.

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