Persistent eosinophilic inflammation is not a feature of Type 2 CRS patients failing anti-IL-5R therapy and requiring class switching to Anti-IL-4/13

Background: Type 2 inflammation dominates eosinophilic chronic rhinosinusitis (eCRS) and adult onset asthma. IL-4, -5, and -13 are prominent disease mediators. Disease control can be achieved with biologic therapies. However, despite some patients entering remission, others experience poor control. Aim: We aimed to describe eCRS patients treated with anti-IL-5R antibody (benralizumab) and assess characteristics between responders and those requiring class switching to anti-IL-4/13R (dupilumab). Method: A retrospective cohort study was performed on consecutive adult patients with eCRS and asthma who had commenced benralizumab. Disease control was defined as controlled or poorly controlled (EPOS2020 partly control/uncontrolled). Poorly controlled patients were switched to dupilumab. Baseline and post-IL-5R characteristics including age, sex, 22-item Sinonasal Outcome Test (SNOT-22), Asthma Control Questionnaire (ACQ) score, and serum/tissue eosinophilia were assessed. Disease control post-class switching was reassessed. Factors predicting poorly controlled disease on anti-IL-5R therapy were sought. Results: Fifty patients were assessed (51.44 ± 12.73 years, 56% female). Poorly controlled disease on anti-IL-5R requiring class switch to dupilumab was seen in 42%. Poorly controlled patients were younger (46.14 ± 10.76 vs. 55.28 ± 12.83 years, p = 0.01) with higher baseline SNOT-22 (61.42 ± 19.19 vs. 42.32 ± 21.55, p < 0.01). Baseline ACQ scores and eosinophil count (0.78 ± 0.49 vs. 0.62 ± 0.34 × 10⁹cells/L, p = 0.23) and were similar between groups. In the poorly controlled patients on anti-IL-5R therapy, eosinophilia had reduced in both serum (0.78 ± 0.5 vs. 0.02 ± 0.1 × 10⁹cells/L, p < 0.01) and tissue (>100 cells/HPF: 100% vs. 29%, p = 0.01). Class switching resulted in disease control for 65%. Conclusion: Neither eosinophilia nor its reduction predicted a non-responder group to anti-IL-5R therapy. While the eosinophil population may be a good marker for the CRS phenotype seen in nasal polyps, it is unlikely to be the cell population driving the disease process.