Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell

Circulating microRNAs In Hereditary Hemorrhagic Telangiectasia: Preliminary Results Identify Significant Differences Among Patients

Objectives: We are investigating the role of circulating microRNAs (miRNAs) in HHT as potential disease biomarkers. The main goal is to define an HHT-related miRNAs signature. Particular attention has been paid on miRNAs-genotype and miRNAs-phenotype correlations. Here we present the preliminary results of this study. Methods: We performed a circulating miRNAs profiling in 15 subjects: 5 HHT1, 5 HHT2 Patients, and 5 controls, age and gender matched. miRNAs profile was analysed by qPCR, using serum/plasma microRNA PCR Panel (I + II), V4.M (Exiqon). Each panel contains 752 LNA™ primer sets of human miRNAs, including different controls. Statistical analyses were performed using parametric and non-parametric methods. miRNAs with a p value\0.05 were considered statistically significant and underwent enrichment analysis. Results: The overall result was the detection of 18 deregulated miRNAs. We observed differences between: HHT Patients versus controls; either HHT1 or HHT2 versus controls; HHT1 versus HHT2 Patients and also comparing Patients’ subgroups showing different clinical features. The enrichment analysis identified the top predicted target genes and the related pathways. Among these, we highlighted different pathways already described in association with HHT or angiogenesis. Conclusions: We obtained a preliminary “HHT signature” for circulating miRNAs, underlying, for the first time, differences between the two disease subtypes and a more peculiar miRNAs profile in HHT2. We also described miRNA-PAVMs (Pulmonary Arteriovenous Malformations) correlations. Confirmation of these results in a larger cohort of patients is therefore mandatory, and Patients enrolment for the second step of this study is ongoin

Guidelines for vascular anomalies by the Italian Society for the study of Vascular Anomalies (SISAV)

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