Biomarkers of type 2 inflammation as predictors of response to biologics for severe eosinophilic asthma.

Abstract

Background: The relationship between pre-treatment levels of blood eosinophil count (BEC), fractional exhaled nitric oxide (F _ENO) and sputum eosinophils (Sp-EOS) and treatment response to monoclonal antibodies (mAbs) in severe eosinophilic asthma (SEA) remains unclear. We evaluated pre-treatment levels of BEC, F _ENO, Sp-EOS and their combinations as predictors of treatment responses in patients with SEA undergoing anti-interleukin (IL)-5/IL-5Rα or anti-IL-4Rα antibody therapies.

Methods: The study included 153 adult patients with SEA (59 anti-IL-5/IL-5Rα and 94 anti-IL-4Rα users). Logistic regression models were used to evaluate the association between predictors and 12-month treatment responses and clinical remission across four domains: exacerbation rate, maintenance of oral corticosteroid dose, forced expiratory volume in 1 s (FEV₁) and asthma control test (ACT) improvement.

Results: Pre-treatment BEC and Sp-EOS were not associated with treatment responses in either mAb group. For combined data from anti-IL-5/IL-5Rα and anti-IL-4Rα users, the adjusted odds ratios (95% confidence intervals) for a 1-unit increase in log-transformed F _ENO were 1.8 (1.21-2.74) for FEV₁ response and 2.15 (1.29-3.75) for ACT response. For anti-IL-4Rα users, these values were 2.34 (1.39-4.17) and 3.6 (1.73-8.84), respectively. No significant association between F _ENO and treatment response was found among anti-IL-5/IL-5Rα users. Additionally, no associations were observed between BEC, Sp-EOS or F _ENO and clinical remission across mAb categories. Combining biomarkers did not significantly enhance predictive ability.

Conclusion: In patients with SEA treated with anti-IL-4Rα antibodies, pre-treatment F _ENO may be a good predictor for certain treatment response domains.