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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Rhinosinusitis With Nasal Polyps
• Intervention / Treatment: Drug: Dupilumab 300 MG/2 ML Subcutaneous Solution [DUPIXENT]

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy
    • AUSL Bologna
  • Catania, Italy
    • Azienda Ospedaliero-Universitaria Policlinico S. Marco
  • Latina, Italy
    • AUSL Latina
  • Milan, Italy
    • ASST Santi Paolo e Carlo - Presidio San Paolo
  • Milano, Italy
    • IRCCS San Raffaele
  • Milano, Italy
    • IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Modena, Italy
    • Azienda Ospedaliero-Universitaria di Modena
  • Napoli, Italy
    • A.O.R.N. Ospedali dei Colli
  • Napoli, Italy
    • Azienda Ospedaliera Policlinico Federico II
  • Novara, Italy
    • Ospedale Maggiore di Novara
  • Orbassano, Italy
    • Ospedale S.Luigi Gonzaga, Università di Torino
  • Padova, Italy
    • Azienda Ospedaliero-Universitaria di Padova
  • Pavia, Italy
    • Policlinico San Matteo-Università di Pavia
  • Pisa, Italy
    • Azienda Ospedaliero-Universitaria Pisana
  • Reggio Emilia, Italy
    • Azienda USL - IRCCS di Reggio Emilia
  • Roma, Italy
    • Università La Sapienza
  • Roma, Italy
    • ASL Roma 5
  • Roma, Italy
    • Fondazione Policlinico Universitario A.Gemelli IRCCS
  • Sassari, Italy
    • Azienda Ospedaliero-Universitaria di Sassari

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

We included all the patients that were referred to Dupilumab therapy, prescribed accordingly to the plan provided by Italian Agency of Drugs.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe, uncontrolled CRSwNP patients in therapy with Dupilumab	Drug: Dupilumab 300 MG/2 ML Subcutaneous Solution [DUPIXENT]; Dupilumab 300mg in pre-filled injector Q2W

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2021
• Primary Completion (Actual): October 1, 2022
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: September 2, 2022
• First Submitted That Met QC Criteria: September 6, 2022
• First Posted (Actual): September 7, 2022

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: February 16, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Nose Diseases; Polyps; Nasal Polyps; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: 0034704/21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No