AUTHOR=Lyly Annina , Sahlman Johanna , Pajala Karoliina , Salminen Maija , Sillanpää Saara , Numminen Jura , Hanif Tanzeela , Laulajainen-Hongisto Anu , Mäkelä Mika , Kauppi Paula , Kangasniemi Iiris , Lilja Markus , Hammaren-Malmi Sari , Virkkula Paula , Toppila-Salmi Sanna 

TITLE=Study protocol for a randomized double-blinded placebo-controlled trial on mepolizumab for patients with chronic rhinosinusitis with nasal polyps, NSAID exacerbated respiratory disease and asthma

JOURNAL=Frontiers in Allergy

VOLUME=Volume 6 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/allergy/articles/10.3389/falgy.2025.1568081

DOI=10.3389/falgy.2025.1568081

ISSN=2673-6101

ABSTRACT=BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease of the nose and paranasal sinuses that significantly impactshealth-related quality of life. Nonsteroidal anti-inflammatory drug (NSAID) -exacerbated respiratory disease (N-ERD) affects approximately one fifth of CRSwNP patients. N-ERD and asthma increase the risk of uncontrolled CRSwNP as measured by frequent sinus surgeries and rescue treatment. Compared to non-N-ERD patients, those with N-ERD also have higher risk of asthma exacerbations, severe allergic reactions, and anosmia. Mepolizumab is a humanized monoclonal anti-IL-5 antibody shown to be effective in treating severe eosinophilic asthma and CRSwNP. While evidence suggests that mepolizumab alleviates respiratory symptoms in N-ERD patients, placebo-controlled studies remain limited.MethodsThe aim of this prospective randomized, placebo-controlled, multicenter study is to investigate whether mepolizumab reduces polyp size, symptom scores, and exacerbations more than placebo during the 16-week treatment period in patients with uncontrolled CRSwNP, N-ERD and asthma. Additionally, we will examine the effect of mepolizumab on drug dosage and lung and nasal function and evaluate predictive biomarkers.We will recruit 120 patients with N-ERD, nasal polyposis and asthma in three centers in Finland. Patients will be randomized into two 16-week treatment groups in 1:1 ratio (placebo or mepolizumab 100 mg every 4 weeks). The study lasts for 6 months, including recruitment visit 2–4 weeks before randomization. Participants will attend 6 visits, during four of which they will receive a subcutaneous injection of the study product. At each visit, patient-reported outcome tests, clinical examination, airway function tests, and nasal, blood, urine, and stool samples will be conducted.DiscussionThe efficacy of the 16-week anti-IL-5-treatment in this severe patient group will be analyzed, as well as possible predictive biomarkers.Clinical Trial registrationClinicalTrials.gov ID NCT04823585. Registered on 28.3.2021.