Journal of Asthma and Allergy (May 2022)
Increase in FeNO Levels Following IL5/IL5R-Targeting Therapies in Severe Asthma: A Case Series
Abstract
Geneviève Pelletier,1 Krystelle Godbout,1,2 Marie-Ève Boulay,1 Louis-Philippe Boulet,1,2 Mathieu C Morissette,1,2 Andréanne Côté1,2 1Quebec Heart and Lung Institute – Laval University, Quebec, QC, Canada; 2Department of Medicine, Faculty of Medicine, Laval University, Quebec, QC, CanadaCorrespondence: Andréanne Côté, Quebec Heart and Lung Institute – Laval University, 2725 chemin Sainte-Foy, Quebec, QC, G1V 4G5, Canada, Tel +1 418 656 4747, Fax +1 418 656 4762, Email [email protected]: Monoclonal antibodies targeting interleukin-5 (IL5) and its receptor (IL5R), used for severe asthma treatment, reduce eosinophils to almost complete depletion. Fractional exhaled nitric oxide (FeNO), a surrogate marker of eosinophilic airway inflammation, is expected to decrease after their initiation. Our center noticed increased FeNO levels in a few patients in whom anti-IL5/IL5R therapy was initiated. Limited data are available on the kinetics of T2 inflammation biomarkers after initiation of a biologic in that population. This study aims to identify if a subgroup of severe asthma patients experiences increased FeNO levels after initiation of anti-IL5/IL5R therapy and to describe their clinical characteristics.Patients and Methods: This is a retrospective case series of 5 patients on Benralizumab (4M:1F) and 8 on Mepolizumab (5M:3F) who showed a significant increase in FeNO (> 20% AND > 25 ppb) following initiation of an anti-IL5/IL5R treatment. Clinical data, expiratory flows, and inflammation were extracted from the patients’ chart at initiation of treatment (T0), 3 months (T1) and 12 months (T2) post-treatment. Descriptive statistics were used.Results: In patients treated with Benralizumab, the increase in FeNO was observed between T0 and T1 (mean delta = 82 ± 72 ppb) with a subsequent decrease (N = 3). In most patients taking Mepolizumab (N = 6), the FeNO increase was observed between T1 and T2 (mean delta = 57 ± 35 ppb). Under treatment, no Benralizumab patient experienced asthma exacerbation while two on Mepolizumab did. All patients had a significant decrease in blood eosinophils.Conclusion: Although initiation of anti-IL5/IL5R may cause a transient rise in FeNO levels in a subgroup of patients, it does not appear to affect clinical outcomes. A compensatory mechanism involving other inflammatory pathways such as IL13 or IL4, both involved in FeNO production, could theoretically explain these findings. Further investigation is needed to elucidate the actual underlying mechanisms.Keywords: biologics, biomarkers, Benralizumab, Mepolizumab
