Biomarkers of Response to Mepolizumab Treatment in Patients With Nasal Polyps With or Without Bronchial Asthma

Mepolizumab is a biologic agent already approved for severe asthma. Recently, there is increasing evidence concerning the benefit of anti-IL5 treatments upon patients with nasal polyposis with or without severe asthma. The novelty of this project is that no biologic agent has yet been fully investigated to identify any biomarkers of response for patients with nasal polyps with or without asthma including sinonasal tissue remodeling a key element in the resultant histopathological changes of the inflammation. The investigation of airway remodeling of various locations (nose and bronchus) under mepolizumab treatment will be our primary objective on the long-term basis of 156 weeks of treatment. Endobronchial and nasal biopsies will be performed as routine care for tissue evauation and disease investigation for every patient. Besides, the united airways will provide better guidance for medical treatment of chronic rhinosinusitis (CRS) patients with nasal polyps (CRSwNP) and asthma. The initial idea is based on investigating the characteristics that could predict the effectiveness of mepolizumab on patients with nasal polyposis with or without asthma. Patients will receive 39 doses of mepolizumab for 156 weeks. An additional aim of this study is to identify characteristics of non-responders and responders to mepolizumab. Responders will be identified based on airway remodeling status, biomarkers in tissue and secretion samples and on the reduction of the need of surgery through Lund-Kennedy endoscopic score, Lund-Mackay score and patient's clinical status in the 6th, 12th and 36th month after the initiation of treatment. Regarding the unified airway system, nose and pharyngeal microbiome will be evaluated before and after 52 weeks of mepolizumab treatment in patients with nasal polyps whereas in patients with nasal polyps and asthma bronchus microbiome will also be evaluated. Lung samples will help gain information about the inflammatory profile and local microbiome of CRSwNP patients with asthma through molecular and cellular assays. The human Pharyngeal Microbiome might play a protective role in Respiratory Tract Infections and it has been reported that the microbiome provides critical signals to promote maturation of immune cells and differentiation of the tissue. Thus, we will make an effort to correlate microbiome of various locations with clinical and laboratory characteristics of responders and non-responders to mepolizumab treatment.

NCT Number	NCT05708300
Lead Sponsor	Aristotle University Of Thessaloniki Collaborators: Department of Otorhinolaryngology, Head and Neck Surgery, George Papanikolaou Hospital, Department of Otorhinolaryngology, Democritus University of Thrace, Alexandroupolis, Department of Pulmonology, Democritus University of Thrace, Alexandroupolis, Respiratory Medicine Department, University of Ioannina, Faculty of Medicine, National and Kapodistrian University of Athens, Department of Allergy and Clinical Immunology, 424 General Military Training Hospital, Department of Otolaryngology, Head and Neck Surgery, Sotiria General Hospital
Conditions	Chronic Rhinosinusitis With Nasal Polyps, Asthma
Enrollment	57 participants
Start Date	2024-02-23
Primary Completion	2026-03-01 (estimated)
Study Completion	2027-03-01 (estimated)
Updated on ClinicalTrials.gov	2024-03-08