Sinonasal Outcomes Obtained after 2 Years of Treatment with Benralizumab in Patients with Severe Eosinophilic Asthma and CRSwNP: A "Real-Life" Observational Study.

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.

Dupilumab Improves Facial Pain and Reduces Rescue Treatments in Patients with CRSwNP and Recalcitrant Frontal Sinusitis.

Recalcitrant frontal sinusitis in patients with chronic rhinosinusitis and nasal polyps (CRSwNP) has a negative impact on their quality of life due to frontal pain and a high risk of sinus occlusion, thus necessitating antibiotics, systemic corticosteroids, and multiple surgeries. The aim of this study was to assess the efficacy of dupilumab in reducing frontal pain and the need for rescue treatments for recalcitrant frontal sinusitis in patients with CRSwNP. We enrolled a cohort of 10 patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis associated with severe facial pain measured by MIDAS score who were treated with dupilumab 300 mg every 2 weeks and followed for at least 12 months. The mean MIDAS score decreased from 45.6 ± 10.7 at baseline to 1.3 ± 2.3 at 6 months (p < 0.05). VAS craniofacial pain decreased from 7.3 ± 1.6 at baseline to 1.2 ± 1.5 at 6 months (p < 0.05). No patient needed oral corticosteroids during treatment with dupilumab (p < 0.05), and the use of analgesics decreased from 9.6 ± 3.1 NSAID pills/week in the last 2 months at baseline to 0.6 ± 1.3 at 1 year of follow-up (p < 0.05). Our results demonstrated that use of subcutaneous dupilumab can improve symptom control, including recurrent severe cranio-facial pain, and reduce the need for rescue medical treatments (systemic steroids and NSAID) in patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis.

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.

Targeting IL-4 and IL-13 Receptors on Eosinophils in CRSwNP Patients: The Clinical Efficacy of Dupilumab.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease linked to type 2 inflammation. Several biologics have demonstrated therapeutic potential for the treatment of this pathology in which IL-4, IL-5 and IL-13 represent the major cytokines involved in the control of eosinophilic respiratory inflammation. 25% of CRSwNP patients relapse after the use of oral glucocorticoids or after surgery and often require several surgeries during their lifetime. In our study we enrolled 14 patients, 11 male and 3 female. The inclusion criteria were: age ≥ 18 years; confirmed diagnosis of chronic rhinosinusitis with severe nasal polyposis; disease severity with NPS Nasal Polyposis Endoscopic Score total score ≥ 5 and/or SNOT-22 ≥ 50; previous treatment failure due to lack of efficacy or discontinuation of systemic corticosteroid therapy and/or non-response or recurrence following surgery. The results presented in this study showed the ability of Dupilumab to improve all the parameters analysed. In particular, statistically significant data were obtained for NPS, SNOT-22, NRS, and IgE in patients exposed to Dupilumab treatment for 24 weeks, highlighting the ability of Dupilumab to produce clinical benefit in CRWwNP patients. In light of these data, the administration of dupilumab every two weeks represents a valid clinical strategy that ENT specialists can adopt for the treatment of adults with inadequately controlled CRSwNP.