Mepolizumab in the Treatment of Patients With Severe Uncontrolled CRSwNP: a Multicentric Real Life Observational Study (MEPOREAL)

Effectiveness of Mepolizumab in the Treatment of Patients With Severe Uncontrolled CRSwNP: a Multicentric Real Life Observational Study

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a complex chronic inflammatory disease of the nasosinusal mucosa that has a significant negative impact on patients' quality of life.

In CRSwNP, chronic inflammation is primarily driven by type 2 pro-inflammatory interleukins (ILs )such as IL-5, IL-4, and IL-13 along- side high levels of eosinophils in the surrounding tissue. Mepolizumab is a targeted, humanized anti-IL-5 antibody that prevents IL-5 from binding to its receptor on eosinophils and selectively inhibits eosinophilic inflammation.

So far, randomized clinical trials have assessed efficacy and safety of Mepolizumab in a large number of patients, whereas evidences in real life clinical practice are limited to few monocentric series.

Herewith, we present a multicenter, observational, prospective/retrospective nationwide real-life study with the aim to confirm the effectiveness and the safety of Mepolizumab over the first year of treatment in a real life setting.

The primary objective of this study is to evaluate the reduction of dimension of nasal polyps and the improvement of quality of life in the patient measured through symptomatologic questionnaires.

The secondary objective is to evaluate improvements in terms of smell dysfunction, comorbidities, biomarkers (nasal cytology and blood eosinophilia), need of surgery or systemic steroids.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Rhinosinusitis With Nasal Polyps
• Intervention / Treatment: Drug: Mepolizumab Auto-Injector

• Study Type: Observational
• Enrollment (Estimated): 199

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy
    • Ospedali PO di Venere e San Paolo
  • Bari, Italy
    • Policlinico Universitario di Bari, Ospedale Giovanni XXIII,
  • Bologna, Italy
    • AUSL Bologna
  • Brescia, Italy
    • ASST degli spedali civili di Brescia,
  • Catania, Italy
    • Azienda Ospedaliero Universitaria Policlinico - S. Marco,
  • Firenze, Italy
    • Azienda Ospedaliero Universitaria Careggi
  • Genova, Italy
    • Ospedale Policlinico San Martino,
  • Lecce, Italy
    • Ospedale Vito Fazzi, ASL Lecce
  • Milano, Italy
    • IRCCS Ospedale San Raffaele
  • Milano, Italy
    • ASST Santi Paolo e Carlo
    • Contact: Carlotta Pipolo
  • Milano, Italy
    • IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Modena, Italy
    • Azienda Ospedaliero-Universitaria di Modena - Modena
    • Contact: Daniela Lucidi
  • Napoli, Italy
    • Azienda ospedaliera policlinico Federico II di Napoli
  • Novara, Italy
    • Ospedale Maggiore della Carità di Novara,
  • Orbassano (TO), Italy
    • Azienda Ospedaliera Universitaria San Luigi Gonzaga,
  • Padova, Italy
    • Azienda Ospedaliera Universita di Padova
  • Pavia, Italy
    • Fondazione I.R.C.C.S. Policlinico San Matteo
    • Contact: Fabio Pagella
  • Pisa, Italy
    • Azienda Ospedaliero-Universitaria Pisana - Pisa
  • Reggio Emilia, Italy
    • Azienda USL - IRCCS di Reggio Emilia
  • Roma, Italy
    • Azienda Ospedaliera San Camillo-Forlanini
  • Roma, Italy
    • Fondazione Policlinico Universitario A.Gemelli IRCCS
    • Contact: Eugenio De Corso; Phone Number: 0630154439; Email: eugenio.decorso@policlinicogemelli.it
  • Roma, Italy
    • Ospedaliero- Universitaria Policlinico Umberto I
  • Roma, Italy
    • Policlinico Tor Vergata: Fondazione PTV
  • Roma, Italy
    • Presidio Ospedaliero San Filippo Neri,
  • Siena, Italy
    • Azienda Ospedaliero- Universitaria Senese
  • Tivoli, Italy
    • i ASL ROMA 5 - Distretto Sanitario di Tivoli
  • Varese, Italy
    • ASST sette laghi Varese,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

We included all patients that were referred to Mepolizumab therapy, prescribed accordingly to the plan provided by AIFA

Description

Inclusion Criteria:

• Patients over 18 years of age who can sign a written informed consent Confirmed clinical / radiological diagnosis of chronic rhinosinusitis with diffuse naso-sinusal polyposis by nasal endoscopy and/or massive facial CT scan without contrast medium carried out within 6 months prior to the start of therapy;
• Blood eosinophils >150
• Severe disease stage, defined by Nasal Polyp Score (NPS) ≥ 5 or nasal obstruction symptom visual analogue scale (VAS) score of >5 and/or Sinonasal outcome tests-22 (SNOT-22) ≥ 50);
• Inadequate symptom control with intranasal local corticosteroid therapy;
• Failure of previous medical treatments (at least 2 cycles in the last year of systemic corticosteroid) and failure of previous surgical treatment through nasal endoscopic surgery (FESS), with no clinical benefit or postoperative complications.

Exclusion Criteria:

• Age <18 years;
• Patients undergoing immunosuppressive therapies;
• Patients undergoing radio/chemotherapy treatments for cancer in the 12 months before the start of therapy;
• Patients on 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 Mepolizumab	Drug: Mepolizumab Auto-Injector; Mepolizumab 100 mg in pre-filled injector; Other Names: Mepolizumab 100 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasal Polyp Score	Evaluation of polyps volume from 0 (minimum) to 4 (maximum) points for each nasal cavity. Reduced score indicates improvement	24 months
Sinonasal Outcome Test - 22	Questionnaire measuring health-related quality of life. The score is from 0 (minimum) to 110 (maximum). Reduced score indicates improvement	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analogue Scale for nasal obstruction	Evaluation of nasal obstruction from 0 (minimum) to 10 (maximum) ;reduced score indicates improvement	24 moths
Nasal Congestion Score (NCS); score (range 0-3);	Evaluation of nasal congestion educed score indicates improvement	24 months
Visual Analogue Scale for smell	Evaluation of olfaction impairment from 0 (minimum) to 10 (maximum); reduced score indicates improvement	24 months
Sniffing sticks identification test	Test of nasal chemosensory performance based on pen-like odor dispensing devices. From 0 (minimum ) to 16 (maximum); increased score indicates improvement.	24 months
Change in blood eosinophil count	Change in blood eosinophil count in a complete blood count (CBC)	24 months
Adherence to drug therapy with Mepolizumab	Number of missing injection in a year	24 months
Need for rescue oral corticosteroids	Number of oral corticosteroids cycles during therapy	24 months
Need for surgery	Number of surgeries performed during therapy	24 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): February 5, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: February 2, 2024
• First Submitted That Met QC Criteria: February 12, 2024
• First Posted (Estimated): February 14, 2024

Study Record Updates

• Last Update Posted (Estimated): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Nose Diseases; Polyps; Nasal Polyps
• Other Study ID Numbers: 6231

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
• product manufactured in and exported from the U.S.: No