Dual REmission in Moderate-to-SEvere asthMa and Nasal Polyps (DREAM-NP)

Background and Rationale

Asthma is a heterogeneous chronic inflammatory airway disease affecting approximately 300 million people worldwide. Roughly 5-10% of patients suffer from severe asthma, leading to significant clinical impact and high resource consumption. Patients with severe asthma often present with comorbidities driven by T2-high (Type 2-high) inflammation, characterized by persistent blood hypereosinophilia and increased tissue expression of IL-5 (Interleukin-5). The most frequent comorbidity is CRSwNP (Chronic Rhinosinusitis with Nasal Polyps). This is often explained by the "unified airway theory," suggesting that the upper and lower airways function as a single unit subjected to similar inflammatory insults. While biologic therapies like dupilumab, which targets IL-4/13R (Interleukin-4/13 Receptor), have revolutionized treatment, the goal has shifted toward achieving clinical remission. According to the SANI (Severe Asthma Network Italy), clinical remission in asthma is defined by:

• No further need for OCS (Oral Corticosteroids).
• Absence of exacerbations.
• Stable lung function.
• Absence of symptoms, measured by an ACT (Asthma Control Test) score of 20-25 or an ACQ (Asthma Control Questionnaire) score < 1.5.
• For CRSwNP (Chronic Rhinosinusitis with Nasal Polyps), EUFOREA (European Forum for Research and Education in Allergy and Airway Diseases) defines remission as a condition with an NPS (Nasal Polyp Score) < 4, NCS (Nasal Congestion Severity) < 2, and no need for surgery or systemic corticosteroids after 12 months.

Study Objectives

Primary Objective:

To evaluate the clinical efficacy of dupilumab after 12 months of treatment in patients with comorbid asthma and CRSwNP (Chronic Rhinosinusitis with Nasal Polyps) regarding:

• Percentage of patients in complete clinical remission for asthma according to SANI (Severe Asthma Network Italy) criteria.
• Percentage of patients in complete clinical remission for CRSwNP (Chronic Rhinosinusitis with Nasal Polyps) according to EPOS (European Position Paper on Rhinosinusitis and Nasal Polyps)/EUFOREA (European Forum for Research and Education in Allergy and Airway Diseases) criteria.
• Percentage of patients achieving simultaneous complete clinical remission for both conditions.

Secondary Objectives (at 1, 6, and 12 months):

• Partial clinical remission rates.
• Improvement in disease control scores, specifically ACT (Asthma Control Test) and SNOT-22 (22-Item Sino-Nasal Outcome Test).
• Stabilization of spirometric parameters.
• Reduction in OCS (Oral Corticosteroids) use and annual asthma exacerbation rates.
• Improvement in smell via identification tests.

Study Design and Population This is a no-profit, observational, retrospective, multicenter study. Setting: Adult patients (≥18 years) followed for at least 12 months since starting dupilumab.

Sample Size: Approximately 280 patients across 14 centers. Inclusion Criteria: Diagnosis of CRSwNP (Chronic Rhinosinusitis with Nasal Polyps) per EPOS (European Position Paper on Rhinosinusitis and Nasal Polyps) 2020 and asthma per ERS (European Respiratory Society)/ATS (American Thoracic Society) 2014.

Exclusion Criteria: Conditions contraindicating dupilumab, clinically significant bronchiectasis confirmed by CT (Computed Tomography), or pregnancy/breastfeeding.

Data Management and Statistical Plan Data collection includes four timepoints: baseline, 1 month, 6 months, and 12 months.

Key Variables:

Blood Biomarkers: Blood eosinophils and total IgE (Immunoglobulin E). Functional Tests: FeNO (Fractional exhaled Nitric Oxide) and plethysmography parameters such as FEV1 (Forced Expiratory Volume in 1 second), FVC (Forced Vital Capacity), TLC (Total Lung Capacity), and DLCO (Diffusing Capacity for Carbon Monoxide).

Statistical Analysis:

Descriptive statistics will be used for all baseline and follow-up characteristics. Normality will be assessed via the Shapiro test. A Bayesian method will be applied to manage missing data and cluster the population to control for confounding factors.