Pre-biologic FeNO might predict anti-IL-5/IL-5Rα response to treatment in severe asthmatics

Objective: It remains unclear whether baseline FeNO levels can predict response to anti-IL5/5R biologic treatment in patients with severe asthma. Methods: We recruited 104 patients with severe eosinophilic asthma treated with anti-IL5/anti-IL5R for at least one year who had measured FeNO values before the beginning of anti-eosinophilic treatment. Population was divided into subjects with FeNO < 25 and ≥25 ppb. In each group we evaluated the changes in pulmonary function (FEV1% and FEF25-75%), clinical (ACT and exacerbations) and steroid-sparing effect, expressed as the modification of daily dosage of inhaled corticosteroids (ICS) and oral corticosteroids (OC), after anti-IL5/anti-IL5R. Results: FEV1 changes after treatment were 3.34 ± 15,97% in subjects with low baseline FeNO, whereas 11.2 ± 16.1% in individuals with FeNO ≥ 25 ppb (p = 0.012). Also, FEF25-75% variations after treatment were different in the two groups: 2.1 ± 10.7% vs 9.6 ± 18% in individuals with FeNO < 25 and ≥25 respectively (p = 0.05). Conversely, ACT (4.4 ± 4.2 vs 5.9 ± 4.6; p = 0.147), exacerbation changes (-2.46 ± 1.5 vs -2.9 ± 1.6; p = 0.137) after treatment were similar in both groups where ICS dosages reduction was alike. On the contrary, the percentage of subjects that reduced/stopped OC treatment after anti-IL5/anti-IL5R was 71.7% in the group with FeNO < 25 ppb whereas 94.1% in individuals with FeNO ≥ 25 (p = 0.06). Multivariate analysis adjusted for all confounding factors also confirmed the relationship between FeNO ≥ 25 and improvement in FEV1%/FEF25-75% (β = 8.372, p = 0.013 and β = 8.883; p = 0.062 respectively) and the increased probability of discontinuing/reducing OC use (OR:17.838 [95%CI:3.159-100.730]; p = 0.001) in the high FeNO group. Conclusion: Pre-biologic FeNO might predict a greater response to treatment with anti-IL-5/5R especially in terms of lung function and OC sparing in subjects with severe eosinophilic/allergic asthma. This could likely be a biomarker that can better guide in choosing an anti-IL5/5R in severe overlapping asthma (eosinophilic/allergic) to maximize treatment effects.