BACKGROUND: Monoclonal antibodies have been proposed as a novel therapy in patients suffering from chronic rhinosinusitis with nasal polyposis (CRSwNP). The purpose of this systematic review was to evaluate their efficacy and safety.METHODOLOGY: A literature search was performed in MEDLINE, Web of Science, the Cochrane Library and multiple trial registries followed by extensive hand-searching for the identification of relevant studies. Only randomized controlled trials (RCTs) comparing the use of monoclonal antibodies with placebo or another therapy in adult patients with CRSwNP were included.RESULTS: Anti-immunoglobin E (IgE) therapy with omalizumab was assessed in two studies, anti-interleukin (IL)-5 therapy in three studies (1 reslizumab, 2 mepolizumab) and finally anti-IL-4 and anti-IL-13 therapy in only one. With the exception of one study, biologic therapy was proved to be effective in reducing total nasal endoscopic polyp score (TPS) in treatment as compared to placebo groups. Monoclonal antibodies brought about improvement in several other outcomes, such as opacification in computed tomography (CT), quality of life measures, nasal airflow, olfaction and type 2 helper T-cell (Th2) associated biomarkers. Overall, the use of these agents was deemed safe and well-tolerated.CONCLUSIONS: This is the first systematic review showing encouraging results for the use of all three main categories of monoclonal antibodies in CRSwNP patients and highlights the need for further well-designed and with larger sample sizes RCTs.