Use of FeNO to predict anti-IL-5 and IL-5R biologics efficacy in a real-world cohort of adults with severe eosinophilic asthma

Abstract

Introduction

Severe eosinophilic asthma (SEA) is associated with multiple exacerbations. Fractional exhaled nitric oxide (FeNO), a biomarker of airway T2 inflammation, is known to be correlated with the risk of exacerbations. While the use of FeNO is well established to predict the therapeutic response to dupilumab (anti-IL-4/IL-13), it remains uncertain for biologics targeting the IL-5 pathway.

Methods

We conducted an observational, retrospective, monocentric analysis of adults with SEA who started mepolizumab (anti-IL-5) or benralizumab (anti-IL-5R) between January 1, 2016 and December 31, 2020.

Results

Data were collected for 109 patients. All participants reported uncontrolled asthma with a median of 3 annual exacerbations and a median Asthma Control Test score of 12. They all had an initial blood eosinophilia >300/mm³, with a median at 610/mm³ (IQR 420-856). Patients with a baseline FeNO ≥50 ppb reported more exacerbations in the previous year than those with a FeNO <50 ppb (p = 0.02). After initiation of treatment, change in FeNO was not associated with therapeutic response. However, decrease in the annual number of exacerbations was significantly greater in patients with a baseline FeNO ≥50 ppb than in those with a baseline FeNO <50 ppb (-3.3 ± 2.7 vs −0.9 ± 2.4, respectively; p = 0.01). There was no association between baseline FeNO values and subsequent lung function, asthma control or reduction of oral corticosteroids use.

Conclusion

In this real-world cohort, adults with SEA who had a baseline FeNO ≥50 ppb experienced a greater decrease in exacerbations after 12 months of anti-IL-5 or IL-5R biologics than those with a FeNO <50 ppb.

Keywords:

• Exhaled nitric oxide
• severe asthma
• interleukin-5
• mepolizumab
• benralizumab
• exacerbation

Acknowledgements

The authors thank the LUNG innOvatiOn (LUNG O₂) research cluster for logistic support.

Declaration of interest

SD has received honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, GSK. AC has received honoraria for speaking at sponsored meetings from GSK, Novartis, Menarini, Chiesi. DH had support for attending meetings and/or travel from Sanofi, Novartis, GSK and AstraZeneca. AMo has received honoraria for speaking at sponsored meetings from Sanofi. AMa has received honoraria for speaking at sponsored meetings from Sanofi, AstraZeneca, GSK, Novartis. FXB had support to travel and attend international conferences from AstraZeneca. There were no potential conflicts of interests with respect to research, authorship and/or publication of this paper. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding

The authors reported there is no funding associated with the work featured in this article.