Phenotypic Predictors of Response to IL-5 Pathway Inhibitors in Severe Eosinophilic Asthma: A Retrospective Real-World Cohort

ObjectiveTo identify real-world clinical and phenotypic predictors of treatment response to interleukin-5 (IL-5) pathway inhibitors in adults with severe eosinophilic asthma.MethodsIn this retrospective cohort study, 128 adults with severe eosinophilic asthma treated with mepolizumab or benralizumab were followed for at least 12 months between June 2019 and June 2025. Treatment response was evaluated using a multidimensional composite outcome incorporating asthma control, exacerbation frequency, and oral corticosteroid reduction. Independent predictors of response were identified using multivariable logistic regression and sensitivity analyses.ResultsDuring follow-up, most patients achieved clinically meaningful improvement. In adjusted analyses, baseline blood eosinophil counts were excluded from the primary multivariable model because they may have been influenced by systemic corticosteroid use. Nasal polyposis (OR = 5.01; 95% CI: 1.28-19.59) and earlier age at asthma onset (OR = 0.92 per year; 95% CI: 0.86-0.98) were independently associated with treatment response. Obesity and total IgE levels were not independently associated with response in the fully adjusted model. Sensitivity analyses incorporating baseline blood eosinophil counts and prior exacerbation frequency yielded consistent findings.ConclusionsNasal polyposis and earlier disease onset represent key phenotypic markers associated with a favorable response to IL-5-targeted biologic therapy. These findings support phenotype-oriented strategies for biologic selection and personalized management in routine clinical practice.