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

Bruno Sposato; Marco Scalese; Gianna Camiciottoli; Giovanna Elisiana Carpagnano; Corrado Pelaia; Pierachille Santus; Girolamo Pelaia; Paolo Cameli; Elena Bargagli; Leonardo Gianluca Lacerenza; Dejan Radovanovic; Paola Rogliani; Mauro Maniscalco; Simonetta Masieri; Carlo Cavaliere; Angelo Guido Corsico; Nicola Scichilone; Stefano Baglioni; Antonio Perrella; Pierluigi Paggiaro; Alberto Ricci

doi:10.1080/02770903.2025.2451691

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

J Asthma. 2025 Jan 9:1-8. doi: 10.1080/02770903.2025.2451691. Online ahead of print.

Authors

Bruno Sposato¹, Marco Scalese², Gianna Camiciottoli³, Giovanna Elisiana Carpagnano⁴, Corrado Pelaia⁵, Pierachille Santus⁶, Girolamo Pelaia⁷, Paolo Cameli⁸, Elena Bargagli⁸, Leonardo Gianluca Lacerenza⁹, Dejan Radovanovic^{6

10}, Paola Rogliani¹¹, Mauro Maniscalco¹², Simonetta Masieri¹³, Carlo Cavaliere¹⁴, Angelo Guido Corsico¹⁵, Nicola Scichilone¹⁶, Stefano Baglioni¹⁷, Antonio Perrella¹, Pierluigi Paggiaro¹⁸, Alberto Ricci¹⁹

Affiliations

¹ Pneumology Department, Azienda USL Toscana Sud-Est, "Misericordia" Hospital, Via Senese 161, 58100 Grosseto, Italy.
² Clinic Physiology Institute, National Research Centre, 56124 Pisa, Italy.
³ Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence - Severe Asthma Unit, Careggi University Hospital, Florence, Italy.
⁴ Institute of Respiratory Disease, Department of Translational Biomedicine and Neuroscience, University "Aldo Moro", Bari, Italy.
⁵ Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Calabria, Italy.
⁶ Division of Respiratory Diseases, "L. Sacco" University Hospital, Università degli Studi di Milano, 20122 Milano, Italy.
⁷ Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy.
⁸ Respiratory Diseases Unit, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Tuscany 53100, Italy.
⁹ Unit of Local Health, Pharmaceutical Department, USL Toscana Sud Est, Grosseto, Italy.
¹⁰ Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20122 Milano, Italy.
¹¹ Unit of Respiratory Medicine, Department of Experimental Medicine, The University of Rome 'Tor Vergata', Rome, Italy.
¹² Istituti Clinici Scientifici Maugeri IRCCS, Pulmonary Rehabilitation Unit of Telese, Terme Institute, Telese, Italy; Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
¹³ Department of Oral and Maxillofacial Sciences, Sapienza University, 00185 Rome, Italy.
¹⁴ Department of Sense Organs, Sapienza University, 00185 Rome, Italy.
¹⁵ Division of Respiratory Diseases, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
¹⁶ Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), Division of Respiratory Diseases, University of Palermo, Palermo, Italy.
¹⁷ Pulmonary and Respiratory Intensive Care Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.
¹⁸ Department of Surgery, Medicine, Molecular Biology and Critical Care, University of Pisa, Pisa, Italy.
¹⁹ Division of Pneumology, Department of Clinical and Molecular Medicine, Sapienza University of Rome, AOU Sant'Andrea, 00189 Rome, Italy.

PMID: 39783623
DOI: 10.1080/02770903.2025.2451691

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 FEF_25-75%), 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, FEF_25-75% 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%/FEF_25-75% ((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).

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; anti-IL-5; anti-IL-5Rα; benralizumab; biologic; mepolizumab; real-life; response; severe asthma.