IL-5/IL-5R blockade enables safe non-steroidal anti-inflammatory agent reintroduction in non-steroidal anti-inflammatory exacerbated respiratory disease
FRONTIERS IN IMMUNOLOGY, vol.17, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 17
- Publication Date: 2026
- Doi Number: 10.3389/fimmu.2026.1950229
- Journal Name: FRONTIERS IN IMMUNOLOGY
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Directory of Open Access Journals, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Health Research Premium Collection (ProQuest)
- Open Archive Collection: AVESIS Open Access Collection
- Istanbul University Affiliated: Yes
Abstract
Background Biologic therapies targeting the interleukin-5 (IL-5) pathway improve asthma control and chronic rhinosinusitis with nasal polyposis (CRSwNP) in patients with non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD). However, their effect on NSAID tolerance remains insufficiently characterized.Objective This study aimed to investigate whether anti-IL-5/IL-5 receptor (IL-5R) treatments could improve NSAID tolerance in patients with NERD and Blended Reactions (BRs).Method Clinical parameters, including the Asthma Control Test (ACT), 22-item Sino-Nasal Outcome Test (SNOT-22), visual analog scale (VAS) scores for quality of life, nasal polyp grade, and inhaled corticosteroid/long-acting beta 2-agonist (ICS/LABA) dose, were compared before and after biologic therapy. ASA provocation tests were repeated during biologic treatment and compared with prior challenge results; outcomes were also compared between the biologic-treated group and the biologic-naive comparison group.Results Patients who received biological treatments showed significant improvements compared to baseline, with eosinophil counts decreasing from 695 (590-892.5) to 50 (30-60), ACT scores increasing from 12 (8.7-18) to 24 (20.7-24.2), SNOT-22 scores declining from 56 (51-73) to 16 (5.7-28.7), and VAS scores improving from 1 (0-2.2) to 9 (7-10), all with p=0.001. ASA provocation positivity decreased to 28.5% (p=0.002), and all patients stepped down from high-dose to medium/low-dose ICS/LABA. Among the four patients who remained intolerant, reactions occurred at higher cumulative doses, with delayed onset and milder symptoms.Conclusion Our study indicated that blockade of IL-5 pathway significantly improved clinical outcomes and reduced ASA hypersensitivity in patients with NERD/BRs, highlighting their potential role in modifying disease phenotype beyond asthma control.