Nucala controls systemic EGPA, but sinus disease may persist
Real-world study found nasal polyps often remained after 2 years
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Long-term treatment with Nucala (mepolizumab) was linked to systemic disease remission in more than 90% of people with eosinophilic granulomatosis with polyangiitis (EGPA) in a real-world study in Italy, but sinonasal disease often persisted.
Sinonasal manifestations affect the nasal cavity and the paranasal sinuses, the air-filled spaces within the facial bones located near the nasal cavity.
While numbers of immune cells called eosinophils, which are usually high in EGPA, and standard disease activity scores dropped significantly during treatment, many patients continued to have sinonasal manifestations, and nearly one-third required additional sinus surgery to manage the condition.
ENT evaluation may remain important during Nucala treatment
These results suggest that “comprehensive assessment should combine systemic markers with dedicated ENT [ear, nose, and throat] evaluation, while management may require integrated biologic–surgical strategies in chronic structural disease,” the researchers wrote.
The study, “Chronic Rhinosinusitis With Nasal Polyposis in EGPA: A Real-Life Multidimensional Analysis Through Mepolizumab Dosing and Role of Adjunctive Endoscopic Sinus Surgery (ESS),” was published in the International Forum of Allergy & Rhinology.
EGPA is the rarest form of ANCA-associated vasculitis (AAV), a group of autoimmune diseases marked by inflammation and damage to small blood vessels.
This rare type is characterized by granulomas (immune cell clumps), high eosinophil counts, and ENT manifestations. It commonly presents with adult-onset asthma and sinonasal disease, most often chronic inflammation of the nasal passages and paranasal sinuses with noncancerous growths called polyps.
Despite the availability of targeted treatments, sinonasal disease in EGPA patients frequently remains resistant to treatment and may require endoscopic sinus surgery (ESS) — a minimally invasive procedure to remove polyps in the sinuses through the nostrils.
GlaxoSmithKline’s Nucala is an antibody-based therapy that targets interleukin-5 (IL-5), a signaling molecule that promotes eosinophil growth and survival. “Evidence on ENT trajectories under anti-IL5 treatment and role of endoscopic sinus surgery (ESS) remains limited and is often described without standardized assessment tools,” the researchers wrote.
Researchers tracked sinonasal disease over 2 years
To learn more, a team of researchers in Italy retrospectively analyzed data from 52 adults with EGPA, 63.5% of whom were women, who were treated with Nucala for at least two years at a single Italian hospital between September 2017 and September 2025.
Participants had a mean age of 49.6 years when they were diagnosed with EGPA and 57.3 years at the start of Nucala treatment (baseline).
At baseline, 92.31% of patients had ENT manifestations marked by sinusitis (inflammation of the sinuses) and/or nasal polyps, and most had asthma (86.54%) and allergies (61.5%). Most participants were also receiving systemic corticosteroids (92%), and many were on immunosuppressive medications.
Most patients (86.5%) started Nucala at the approved dose of 300 mg, once every four weeks. Seven patients (13.46%) received a dose of 100 mg once every four weeks, as treatment had been initiated previously for another approved indication of Nucala and provided satisfactory disease control. During follow-up, eight patients underwent a dose reduction from 300 to 100 mg (step-down group).
Results showed that systemic disease remission was achieved by more than 90% of the patients, with marked reductions of eosinophil counts and a Birmingham Vasculitis Activity Score (BVAS) of zero. BVAS is a tool used to assess vasculitis disease activity.
However, sinonasal manifestations persisted in 92% of evaluable participants, with 64% still showing nasal polyps. Across the overall study population, there were no significant changes in visible nasal polyp extension and severity, as assessed with the Nasal Polyp Score (NPS).
Sinonasal improvement varied by Nucala dose group
There was a progressive reduction in mean NPS from baseline to one and two years in the 100 mg dose group, from 3.2 to 1.0 and 0.75, and this difference nearly reached statistical significance. In the same group, inflammation seen during nasal endoscopy also significantly improved over time. In contrast, NPS remained stable in the 300 mg dose and step-down groups.
Additionally, patients in the 100 mg group reported a clinically meaningful score reduction in the Sino-Nasal Outcome Test, which measures sinonasal symptom severity and its impact on daily life, although score differences were not significant in any group. Patient-reported outcomes were significantly associated with nasal polyp burden and sinonasal inflammation.
Almost half of the participants (46%) underwent ESS before starting Nucala, and 28.8% required adjunctive ESS while on Nucala.
In an exploratory analysis, the dosing strategy appeared to be associated with adjunctive ESS. The step-down group showed the highest proportion of patients requiring adjunctive surgery (62.5%), followed by the 300 mg group (27%), and the 100 mg group (0%).
“In this real-life EGPA cohort, [Nucala] was associated with improvement in patient-reported sinonasal burden and endoscopic inflammation; however, objective sinonasal disease frequently persisted over 24 months, with a substantial proportion of patients retaining nasal polyps and chronic endoscopic signs, despite robust and sustained control of systemic EGPA activity,” the researchers wrote.
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