The MEPOREAL phase 4 study found that mepolizumab improved disease outcomes in severe, uncontrolled CRSwNP, with 42% achieving disease control at 12 months.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
A multicentre phase 4 study published online in The Lancet Respiratory Medicine found that mepolizumab progressively improved clinical outcomes over 12 months in patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). In the 621-patient MEPOREAL study, 42% of evaluable patients achieved disease control at 12 months, while a further 20% were progressing towards remission.
MEPOREAL Evaluated Mepolizumab in Routine Specialist Practice
MEPOREAL (NCT06258772) was a real-life, ambispective phase 4 study conducted across 25 Italian tertiary referral rhinology clinics experienced in severe CRSwNP and biologic therapies. The participating network included university hospitals and specialist otorhinolaryngology and rhinology centres across multiple Italian regions.
Patients with severe, uncontrolled CRSwNP who started mepolizumab 100 mg every four weeks were assessed at baseline and after 1, 3, 6, 9, and 12 months. The study was sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
The primary outcomes were changes in nasal polyp score and the 22-item Sino-Nasal Outcome Test (SNOT-22). Investigators also assessed symptoms, olfactory function, blood eosinophils, disease control, progression towards remission, comorbid asthma, NSAID-exacerbated respiratory disease (NSAID-ERD), and previous biologic exposure.
Nasal Polyps and Sinonasal Symptoms Improved
Between December 1, 2023, and March 15, 2024, 621 patients received mepolizumab and entered the analysis. At 12 months, both median nasal polyp score and SNOT-22 score had decreased significantly from baseline, with p<0.0001.
Major sinonasal symptoms and measures of olfactory function also improved during treatment. However, recovery of smell remained incomplete for many patients. Among 495 patients assessed for anosmia at 12 months, 186 (38%) remained anosmic.
Patients with comorbid asthma generally experienced greater or faster improvements in SNOT-22 scores and self-reported symptoms, indicating that treatment response varied across clinical subgroups.
Disease Control and Remission Remained Important Long-Term Goals
At 12 months, 206 of 519 evaluable patients (42%) had achieved disease control. Another 104 patients (20%) met the study definition of being on the way to remission, meaning they had met remission criteria but had not yet maintained them for the full 12-month period required to establish remission.
Baseline disease characteristics also influenced outcomes. Higher baseline visual analogue scale smell scores and lower SSIT-16 scores negatively predicted disease control between months 3 and 12. A lower baseline nasal polyp score independently predicted progression towards remission at 12 months, with an odds ratio of 0.72 (95% CI, 0.59–0.87; p=0.0008).
IL-5 Inhibition Targets Eosinophilic Inflammation
Mepolizumab is a humanized monoclonal antibody that blocks interleukin-5 (IL-5), a cytokine that supports eosinophil growth, activation, and survival. By inhibiting IL-5 signalling, mepolizumab reduces eosinophilic inflammation, an important component of type 2 inflammatory CRSwNP. This provides the biological rationale for targeting the IL-5 pathway in patients with severe disease and eosinophilic inflammation.
Safety Profile Remained Favorable
Mepolizumab was well tolerated during the 12-month assessment. Adverse events occurred in 29 of 621 patients (5%), with grade 1 events being the most common.
Longer Follow-Up Needed to Define Remission
The MEPOREAL findings show that clinical improvement with mepolizumab continued progressively through the first year of treatment, while a substantial proportion of patients had not yet reached disease control or sustained remission.
The investigators concluded that longer-term prospective studies are needed to determine the durability of disease control, the rate of sustained remission, and the patient characteristics that best predict long-term response to mepolizumab in severe CRSwNP.
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About the Writer
Shaik Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.