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.
Annina Lyly, Johanna Sahlman, Karoliina Pajala, Maija Salminen, Saara Sillanpää, Jura Numminen, Tanzeela Hanif, Anu Laulajainen-Hongisto, Mika Mäkelä, Paula Kauppi, Iiris Kangasniemi, Markus Lilja, Sari Hammaren-Malmi, Paula Virkkula, Sanna Toppila-Salmi
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Abstract
Background: Chronic 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.
Methods: The 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.
Discussion: The 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 registration: ClinicalTrials.gov ID NCT04823585. Registered on 28.3.2021.
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