Comparative real-world outcomes of dupilumab versus endoscopic sinus surgery in the treatment of severe CRSwNP patients.

INTRODUCTION: Management of severe chronic rhinosinusitis with nasal polyps (CRSwNP) has changed significantly in recent years, with different treatments now available including biologics and endoscopic sinus surgery (ESS), although there are still few comparative studies. We aimed to compare 1-year outcomes of patients with severe CRSwNP treated with dupilumab or ESS plus intranasal corticosteroids (INCS). METHODS: In this retrospective, real-life, observational, cohort study, we enrolled 101 patients with severe CRSwNP who were treated with INCS and either ESS (n = 49) or dupilumab (n = 52). The following outcomes were considered: nasal polyp score (NPS), Sino Nasal Outcome Test-22 (SNOT-22), visual analogue scale (VAS) for specific symptoms, Sniffin' Sticks identification test (SSIT), need for oral corticosteroids (OCS) and local eosinophilia detected by nasal cytology. RESULTS: ΔNPS was significantly higher in the surgery group up to 12 months when the difference with dupilumab group was no longer significant (ΔNPS: 4 vs. 4.1). ΔVAS rhinorrhoea, ΔVAS smell and ΔSNOT-22 were significantly higher in the dupilumab group at 12 months (p < .05). SSIT scores were significantly better in the dupilumab group starting from the first month of follow-up (p < .05). In the dupilumab group, only 6.1% of patients had detectable local eosinophilia compared to 57% in the surgery group alongside with a lower need for OCS (16.3% vs. 61%). CONCLUSIONS: Both dupilumab and ESS were effective in improving outcomes in patients with severe CRSwNP over 12 months. Nevertheless, patients treated with dupilumab had greater improvement in terms of SNOT-22, VAS rhinorrhoea, VAS smell and SSIT scores, with better control of local inflammation and less need for OCS.

Proposal for a Structured Outpatient Clinic for Dupilumab Treatment in Chronic Rhinosinusitis with Nasal Polyps in the First Year of Treatment.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease of the nose and paranasal sinuses with important economic and sanitary burdens, as well as having a great impact on patients' quality of life. In this field, a new therapeutic approach for those patients who have been described as affected by severe uncontrolled CRSwNP, resistant to medical and best surgical treatment, is represented by subcutaneous human monoclonal antibodies (including dupilumab) that block specific targets involved in the type 2 inflammatory pathway which most commonly drives CRSwNP pathophysiology. This paper aims to report our experience in the management of severe uncontrolled CRSwNP and, in particular, describe our diagnostic workup including baseline evaluation and follow-up visits in the first year of treatment. We also describe into detail our multidisciplinary approach to the disease. We finally report the outcomes of treatment in a real-life setting. In this outpatient real-life setting, our results confirmed the effectiveness of dupilumab in reducing the volume of nasal polyps and restoring nasal obstruction and sense of smell, as well as improving patients' quality of life. The adherence to the dupilumab treatment was very high. The dose of administration was never modified in patients in the first year of treatment. All the patients respected the plan of the visits at proposed time points. We believe that the structural organization of our outpatient clinic appears to be functional: it allows us to study patients thoroughly before starting treatment and to make a proper follow-up after it starts. We believe that sharing both our strict clinical flowchart and growing experience with dupilumab with the medical community can lead to more standardized and effective pathways of care for CRSwNP patients.

Effectiveness of Dupilumab in the Treatment of Patients with Severe Uncontrolled CRSwNP: A "Real-Life" Observational Study in the First Year of Treatment.

The aim of this study was to evaluate the efficacy of dupilumab in the treatment of severe uncontrolled Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), with or without asthma as add-on therapy with intra-nasal corticosteroids in a real-life setting over the first year of treatment. Our data demonstrated that subcutaneous 300 mg dupilumab administered at home via a pre-filled auto-injector every two weeks, based on indications set by the Italian Medicines Agency, was rapidly effective in reducing the size of polyps, decreasing symptoms of disease, improving quality of life, and recovering olfaction. Significant improvement was observed after only 15 days of treatment, and it progressively increased at 6 and 12 months. Dupilumab was also effective in reducing the local nasal eosinophilic infiltrate, in decreasing the need for surgery and/or oral corticosteroids, and in improving control of associated comorbidities such as chronic eosinophilic otitis media and bronchial asthma. After 12 months of treatment, 96.5% of patients had a moderate/excellent response. From our data, it was evident that there was a group of patients that showed a very early response within one month of therapy, another group with early response within six months from baseline, and a last group that improved later within 12 months. The results of this study support the use of dupilumab as an effective option in the current standard of care for patients affected by severe uncontrolled CRSwNP.