Dupilumab in the Treatment of Severe Uncontrolled CRSwNP: a Multicentre Observational Real-life Study (DUPIREAL)

Study Overview
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Brief Summary
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Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a sino-nasal chronic inflammatory disease that strongly affects patients' quality of life, especially in difficult-to-treat cases. In severe uncontrolled CRSwNP, the inflammation is mostly driven by a type 2 inflammatory pathway and its management has been rapidly changing during the last 2 years due to Dupilumab approval. It is a fully human monoclonal antibody that binds the alpha subunit of IL-4 receptors (IL-4Rα type 1 and type 2) to inhibit IL-4 and IL-13 signaling. So far, randomized clinical trials have assessed efficacy and safety of Dupilumab in a large number of patients, whereas evidences in real life clinical practice are limited to few monocentric series. Herewith, the investigators present a multicenter, observational nationwide retrospective real-life study with the aim to confirm the effectiveness and the safety of Dupilumab over the first year of treatment in a real life setting. The primary objective is to evaluate the volumetric reduction of polyps by measuring the variation of total Nasal Polyp Endoscopic Score (NPS). The secondary objectives are: the evaluation of changes in nasal symptoms, olfactory function and nasal obstruction the assessment of the patients' quality of life the recording of major and minor complications the evaluation of the response to the therapy, according to EPOS2020 criteria and EUFOREA2021 the assessment of efficacy based on concomitant disease (Asthma and ASA triad) the evaluation of potential predictors of clinical response to the therapy

Official Title
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Effectiveness of Dupilumab in the Treatment of Severe Uncontrolled CRSwNP: a Multicentre Observational Real-life Study (DUPIREAL)

Conditions
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Chronic Rhinosinusitis With Nasal Polyps

Intervention / Treatment
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* Drug: Dupilumab 300 MG/2 ML Subcutaneous Solution [DUPIXENT]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: confirmed diagnosis of diffuse CRSwNP by endoscopy and CT scan performed at least 6 months prior of the therapy; severe disease stage defined by NPS ≥5 or SNOT-22 ≥50; inadequate symptom control with INCS therapy; failure or intolerance of previous medical treatments (at least 2 cycles of systemic corticosteroid in the last year), and/or failure of previous surgical treatment through nasal endoscopic surgery (ESS), with postoperative complications or no clinical benefit Exclusion Criteria: pregnant women; immunosuppressive therapy; patients undergoing radio-chemotherapy treatments for cancer in the 12 months before the starting of therapy; concomitant long-term corticosteroid therapy for chronic autoimmune disorders

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Severe, uncontrolled CRSwNP patients in therapy with Dupilumab<br> | Drug: Dupilumab 300 MG/2 ML Subcutaneous Solution [DUPIXENT]<br>* Dupilumab 300mg in pre-filled injector Q2W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nasal Polyp Score (NPS) | Polyps volume. Range 0-4 for each nostril. Higher score describes a worse condition | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nasal Polyp Score (NPS) | Polyps volume. Range 0-4 for each nostril. Higher score describes a worse condition | 24 months | 
| Nasal congestion score (NCS) | Nasal congestion. Range 0-3. Higher score describes a worse condition | 12 months and 24 months | 
| Sinonasal outcome test (SNOT-22) | Symptoms. Range 0-110. Higher score describes a worse condition | 12 months and 24 months | 
| Sniffin' sticks identification test | Olfaction. Range 0-16. Higher score describes a better condition | 12 months and 24 months | 
| Visual Analog Scale (VAS) for nasal congestion | Nasal congestion. Range 0-10. Higher score describes a more severe symptom | 12 months and 24 months | 
| Visual Analog Scale (VAS) for olfaction loss | Olfaction loss. Range 0-10. Higher score describes a more severe symptom | 12 months and 24 months | 
| Visual Analog Scale (VAS) for craniofacial pain | Craniofacial pain. Range 0-10. Higher score describes a more severe symptom | 12 months and 24 months | 
| Visual Analog Scale (VAS) for sleeping disorders | Sleeping disorders. Range 0-10. Higher score describes a more severe symptom | 12 months and 24 months | 
| Visual Analog Scale (VAS) for rhinorrhea | Rhinorrhea. Range 0-10. Higher score describes a more severe symptom | 12 months and 24 months | 
| Visual Analog Scale (VAS) for quality of life | Quality of life. Range 0-10. Higher score describes a worse quality of life | 12 months and 24 months | 
| Need for surgery | Number of surgeries performed during therapy | 12 months and 24 months | 
| Intranasal corticosteroid adherence | Number of days of suspension of intranasal corticosteroids | 12 months and 24 months | 
| Need for rescue oral corticosteroids | Number of short cycles of oral corticosteroids during therapy | 12 months and 24 months |