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.

The complex pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP) generates a spectrum of phenotypes with a wide variety of inflammatory states. We enrolled 44 very-likely-to-be type 2 CRSwNP patients in order to evaluate the load of inflammation and to analyze human interleukins in nasal secretion. Clinical data were collected to evaluate the severity of the disease. High levels of IL-5, IL-4, IL-6, and IL-33 were detected in all type 2 CRSwNP patients. By analyzing type 2 cytokine profiles and local eosinophil count, we identified two coherent clusters: the first was characterized by high levels of IL-4, IL-5, IL-6, and a high-grade eosinophil count (type 2-high); the second had lower levels of cytokines and poor or absent eosinophilic inflammation (type-2 low). IL-5 levels were significantly higher within the type 2 cytokine and it was the most reliable biomarker for differentiating the two clusters. In type 2-high inflammatory profile clinical scores, the mean number of previous surgeries and need for systemic corticosteroids were significantly higher compared to type 2-low. Our research demonstrated the potential role of type 2 biomarkers, and in particular, of IL-5 in identifying patients with a more severe phenotype based on a high inflammatory load.

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is resistant to conventional treatments and strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of our study is to evaluate the effectiveness of biologics drugs in the control of EOM. This is a retrospective no-profit real-life observational study, involving patients affected by refractory EOM and in treatment with different biologics for concomitant severe eosinophilic asthma or severe uncontrolled CRSwNP (Dupilumab: n = 5; Omalizumab: n = 1; Mepolizumab: n = 1; Benralizumab: n = 1). We analyzed data at baseline and at the 6-month follow-up, including specific nasal and otological parameters. We observed an improvement of all nasal outcomes, including NPS, SNOT-22, VAS, and smell function. Regarding specific otological parameters, we observed a significant reduction in the mean value of COMOT-15 score and of Otitis Severity Score at 6-month follow-up compared to baseline (p < 0.05). Finally, we observed an improvement in terms of air conduction hearing levels during the treatment. Our results demonstrated that anti type-2 inflammatory pathway biologics can be effective in improving symptoms control and in reducing the severity of eosinophilic otitis media when treating coexisting type-2 diseases, such as asthma and or CRSwNP.

Objective. The aim of this study was to evaluate the clinical relevance of absolute eosinophil blood count and eosinophil count by nasal cytology in the context of real-life clinical practice and to determine if they correlate with the severity of symptoms in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Methods. We enrolled 425 patients with CRSwNP followed between January 2015 and April 2023 at the A. Gemelli Hospital Foundation-IRCCS, Rome, Italy. We gathered data on blood and local eosinophil count and correlated the results with clinical features. All patients underwent endoscopy, Visual Analogical Scale (VAS) for main symptoms, and SinoNasal Outcome Test 22 (SNOT-22). Results. We observed significantly higher mean levels of eosinophils in serum and at nasal cytology in patients with CRSwNP and comorbidities (asthma, non-steroidal anti-inflammatory drugs - exacerbated respiratory disease and allergy) compared to those without. Blood eosinophilia was not associated with severity of symptoms, whereas patients with nasal eosinophil count > 5 eosinophils per high-power field at nasal cytology had a significantly higher median specific VAS for nasal symptoms and significantly higher SNOT 22 scores. Conclusions. We demonstrated that blood eosinophil count and nasal cytology may represent useful tools in routine clinical practice to define Type 2 inflammation and that their levels are usually higher in patients with comorbidities. We also showed that blood eosinophilia was not correlated with severity of symptoms, whereas local eosinophil count was associated with high severity of symptoms and high burden on quality of life.

Background/Objectives: Benralizumab is a monoclonal antibody that targets the interleukin-5 receptor (IL-5Rα), leading to the rapid depletion of blood eosinophils. RCTs have demonstrated efficacy in patients with severe eosinophilic asthma (SEA). The aim of this study was to assess the efficacy of benralizumab on sinonasal outcomes in a real-life setting in patients with SEA and concomitant chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: We included 25 patients (mean age: 57.47 years, range: 35–77, F/M = 12:13) who were prescribed 30 mg benralizumab every month for the first three administrations and then every 2 months. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test-22 (SNOT-22) and nasal polyp score (NPS) over a 24-month treatment period. Secondary endpoints included measuring the effects on nasal obstruction and impaired sense of smell. Results: The mean NPS score decreased significantly from 5.11 ± 1.84 at baseline to 2.37 ± 1.96 at 24 months. The mean SNOT-22 decreased from 57 ± 15.30 at baseline to 26 ± 16.73 at 24 months. The SSIT-16 mean score improved with an increase in olfactory performance from 5.23 ± 2.58 at baseline to 7 ± 3.65 at 24 months. Moreover, 8/25 patients (32%) required rescue treatment with systemic steroids and 2 patients required endoscopic sinus surgery. Conclusions: While the improvement may not seem optimal at 12 months, a progressive enhancement was noted during the second year of treatment. Despite our data showing an improvement in quality of life and a reduction in the size of nasal polyps, no significant improvement in olfactory sensitivity was observed. In addition, in several patients, rescue treatments were required to maintain control of nasal and sinus symptoms. A careful risk–benefit assessment is therefore needed when deciding to continue treatment, weighing the potential for further improvement against the risks of complications. Such decisions should always be made in the context of a multidisciplinary team.