Mepolizumab effectiveness for patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps in Italy (MEPOREAL): a real-life, multicentre, phase 4 trial.

BACKGROUND: Real-life data on mepolizumab in chronic rhinosinusitis with nasal polyps (CRSwNP) remain heterogeneous. This large, multicentre study aimed to evaluate mepolizumab effectiveness and safety in patients with severe, uncontrolled CRSwNP. Here, we present the results from the first 12-month treatment. METHODS: This real-life, multicentre, ambispective, phase 4 study was conducted across 25 Italian tertiary referral rhinology clinics experienced in the management of severe, uncontrolled CRSwNP and biological therapies. Patients with severe, uncontrolled CRSwNP who started mepolizumab 100 mg every 4 weeks were enrolled. Demographics and clinical data (symptom scores, olfactory measures, endoscopic findings, laboratory parameters, and comorbidities) were collected at baseline and after 1, 3, 6, 9, and 12 months. Primary outcomes were changes in nasal polyp score and sino-nasal outcome test-22 (SNOT-22). Secondary outcomes and exploratory analyses included changes in symptoms, olfactory function, blood eosinophils, disease control rate, and progression towards remission. We also included subpopulation analyses according to asthma, non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD), and previous exposure to biologics. This study is registered with ClinicalTrials.gov, NCT06258772, and is completed. FINDINGS: Between Dec 1, 2023, and March 15, 2024, 621 patients treated with mepolizumab were enrolled. At 12 months, the median nasal polyp score and SNOT-22 score decreased significantly from baseline (p<0·0001). All major symptoms and olfaction improved, although 186 (38%) of 495 patients remained anosmic. Patients with comorbid asthma showed either greater or more rapid improvements in SNOT-22 and self-reported symptoms. Disease control was reached by 206 (42%) of 519 patients at 12 months, and at the same timepoint, 104 (20%) of 519 patients met the definition of being on the way to remission (ie, patients who met the remission criteria but had not yet completed the required 12-month duration for remission definition). Higher visual analogue scale smell score and lower SSIT-16 score at baseline negatively predicted control at 3-12 months, whereas a lower baseline nasal polyp score was the only independent predictor of progression towards remission at 12 months (odds ratio 0·72, 95% CI 0·59-0·87; p=0·0008). Mepolizumab was well-tolerated: 29 (5%) of 621 patients developed adverse events, with grade 1 adverse events being the most common. INTERPRETATION: Mepolizumab progressively improved outcomes during the first 12 months of treatment. Long-term, prospective studies are warranted to further elucidate the rate of remission and control after 12 months. FUNDING: None.