Dual REmission in Moderate-to-SEvere asthMa and Nasal Polyps (DREAM-NP)
Dual Remission in Patients With Moderate-to-Severe Asthma and CRSwNP Treated With Dupilumab: A 24-Month Real-World Study
Studieoversigt
Status
Intervention / Behandling
Detaljeret beskrivelse
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.
- Ethical Considerations The study will be conducted in accordance with the Declaration of Helsinki. Participation is subject to obtaining free and informed consent, safeguarding data protection rights under GDPR (General Data Protection Regulation) EU (European Union) 679/2016. Researchers report no potential conflicts of interest.
Undersøgelsestype
Tilmelding (Faktiske)
Kontakter og lokationer
Studiesteder
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Treviso
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Montebelluna, Treviso, Italien, 31044
- Azienda ULSS 2 Marca Trevigiana
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Prøveudtagningsmetode
Studiebefolkning
Beskrivelse
Inclusion Criteria:
- All patients with comorbid severe asthma and CRSwNP who initiated treatment with dupilumab at Multidisciplinary Unit during the study period and met the pre-defined inclusion criteria ( diagnosis of severe asthma according to GINA guidelines and concomitant CRSwNP eligible for biological treatment)
- Minimum age 18 years
- Signature of informed consent
Exclusion Criteria:
- Conditions that contraindicate dupilumab therapy (eosinophilic conditions, rheumatologic conditions, helminthic infection, restrictive or interstitial lung disease)
- Diagnosis of clinically significant bronchiectasis (overt diagnosis of bronchiectasis on chest CT)
- Inability or lack of informed consent to participate in the study
- Pregnancy
- Breastfeeding
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
Intervention / Behandling |
|---|---|
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205 patients with comorbid moderate-to-severe asthma and CRSwNP.
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observational study
Retrospective multicentric observational study was performed on a cohort of 205 consecutive adult outpatients with comorbid asthma and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP).
The study involved a total of 13 clinical centers across Italy, coordinated by the Multidisciplinary Pulmonology and Otolaryngology Unit of the S. Valentino Hospital in Montebelluna, Italy.
All participating satellite centers followed a follow-up schedule similar to that of the coordinating center to ensure data consistency.
All patients received dupilumab 300 mg every 15 days.
A 600 mg loading dose was administered exclusively to the severe asthma group, following the approved summary of product characteristics.
Clinical Endpoints and Definitions Data were collected at baseline (T0), 6 months (T6), 12 months (T12), and 24 months (T24).
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Achievement of Dual Remission
Tidsramme: 24 months
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Achievement of Dual Remission: Asthma Remission was defined according to the Severe Asthma Network Italy (SANI) criteria as the simultaneous presence of: (1) no OCS use, (2) no exacerbations, (3) ACT score ≥ 20, and (4) stable pulmonary function (FEV1); CRSwNP Remission was defined according to EPOS/EUFOREA guidelines as: (1) an NPS ≤ 1 and (2) a SNOT-22 score < 40.
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24 months
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Francesco Menzella, Medicine and Surgery, Azienda ULSS 2 Marca Trevigiana
Publikationer og nyttige links
Generelle publikationer
- Fokkens WJ, De Corso E, Backer V, Bernal-Sprekelsen M, Bjermer L, von Buchwald C, Chaker A, Diamant Z, Gevaert P, Han J, Hopkins C, Hox V, Klimek L, Lund VJ, Lee S, Luong A, Mullol J, Peters A, Pfaar O, Reitsma S, Toppila-Salmi S, Scadding GK, Sedaghat AR, Viskens AS, Wagenmann M, Hellings PW. EPOS2020/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP. Rhinology. 2024 Jun 1;62(3):287-298. doi: 10.4193/Rhin23.415.
- Canonica GW, Blasi F, Carpagnano GE, Guida G, Heffler E, Paggiaro P, Allegrini C, Antonelli A, Aruanno A, Bacci E, Bagnasco D, Beghe B, Bonavia M, Bonini M, Brussino L, Caiaffa MF, Calabrese C, Camiciottoli G, Caminati M, Caruso C, Cavallini M, Chieco Bianchi F, Conte ME, Corsico AG, Cosmi L, Costantino M, Costanzo G, Crivellaro M, D'Alo S, D'Amato M, Detoraki A, Di Proietto MC, Facciolongo NC, Ferri S, Fierro V, Foschino MP, Latorre M, Lombardi C, Macchia L, Milanese M, Montagni M, Parazzini EM, Parente R, Passalacqua G, Patella V, Pelaia G, Pini L, Puggioni F, Ricciardi L, Ridolo E, Rolo J, Scichilone N, Scioscia G, Senna G, Solidoro P, Varricchi G, Vianello A, Yacoub MR, Yang B. Severe Asthma Network Italy Definition of Clinical Remission in Severe Asthma: A Delphi Consensus. J Allergy Clin Immunol Pract. 2023 Dec;11(12):3629-3637. doi: 10.1016/j.jaip.2023.07.041. Epub 2023 Aug 7.
- De Corso E, Pasquini E, Trimarchi M, La Mantia I, Pagella F, Ottaviano G, Garzaro M, Pipolo C, Torretta S, Seccia V, Cantone E, Ciofalo A, Lucidi D, Fadda GL, Pafundi PC, Settimi S, Montuori C, Anastasi F, Pagliuca G, Ghidini A, Cavaliere C, Maffei M, Bussu F, Gallo S, Canevari FRM, Paludetti G, Galli J; Dupireal Italian Study Group. Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL). Allergy. 2023 Oct;78(10):2669-2683. doi: 10.1111/all.15772. Epub 2023 May 26.
- De Corso E, Montuori C, Pipolo C, La Mantia I, Pasquini E, Ghidini A, Seccia V, Ottaviano G, Cantone E, Dane G, Garzaro M, Fadda GL, Torretta S, Anastasi F, Canevari FRM, Pagella F, Lucidi D, Cavaliere C, Pagliuca G, Maffei M, Bussu F, Corbo M, D Auria LM, De Maio G, Loperfido A, Gallo S, D Agostino G, Giannarelli D, Galli J; DUPIREAL Italian Study Group. Two-Year Turning Point With Dupilumab in Chronic Rhinosinusitis with Nasal Polyps: Control, Remission, and Tapering Dosage. Allergy. 2026 Feb;81(2):388-401. doi: 10.1111/all.70032. Epub 2025 Aug 30.
- Menzella F, Berti A, Cestaro W, Bosi A, Munari S, Gialdini F, Scandiuzzi Piovesan T, Cottini M, Lombardi C, Corsi L, De Corso E. Dual Remission in Patients with Moderate-to-Severe Asthma and CRSwNP Treated with Dupilumab: A 24-Month Real-World Study. J Clin Med. 2026 Apr 7;15(7):2787. doi: 10.3390/jcm15072787.
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
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Opdateringer af undersøgelsesjournaler
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Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 2025-43 PROT N. 0015184/25
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