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. 2025 Jun;62(6):1007-1012.
doi: 10.1080/02770903.2025.2451691. Epub 2025 Jan 17.

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

Bruno Sposato  1 , Marco Scalese  2 , Gianna Camiciottoli  3 , Giovanna Elisiana Carpagnano  4 , Corrado Pelaia  5 , Pierachille Santus  6 , Girolamo Pelaia  7 , Paolo Cameli  8 , Elena Bargagli  8 , Leonardo Gianluca Lacerenza  9 , Dejan Radovanovic  6   10 , Paola Rogliani  11 , Mauro Maniscalco  12   13 , Simonetta Masieri  14 , Carlo Cavaliere  15 , Angelo Guido Corsico  16 , Nicola Scichilone  17 , Stefano Baglioni  18 , Antonio Perrella  1 , Pierluigi Paggiaro  19 , Alberto Ricci  20
Affiliations

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

Bruno Sposato et al. J Asthma. 2025 Jun.

Abstract

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.

Keywords: FeNO; Severe asthma; anti-IL-5; anti-IL-5Rα; benralizumab; biologic; mepolizumab; real-life; response.

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