High local type-2 inflammation is linked to response in severe asthma treated with anti-Interleukin-5 receptor - 23/05/25

Doi : 10.1016/j.rmed.2025.108151

Catherine Moermans ^a,^b,^⁎ , Nicolas Decerf ^c, Nicolas Javaux ^d, Adrien Onssels ^a, Noémie Bricmont ^a, Romane Bonhiver ^a, France Regnier ^b, Adeline Rosu ^a, Sophie Graff ^b, Sara Gerday ^a, Makon-Sébastien Njock ^a,^b, Virginie Paulus ^b, Françoise Guissard ^b, Stéphanie Ziant ^b, Carole Sanchez ^b, Renaud Louis ^a,^b, Florence Schleich ^a,^b,^e
^a Giga I3, Pneumology Research Group, Liege University, 4000, Liege, Belgium
^b Dept. of Pneumology-Allergology, CHU of Liege, 4000, Liege, Belgium
^c Haute école de la Province de Liège (HEPL), 4000, Liège, Belgium
^d Haute école Charlemagne, 4000, Liège, Belgium
^e Exercise Physiology lab, Department of Physical Activity and Rheabilitation Sciences, University of Liege, 4000, Liege, Belgium

^⁎Corresponding author. Dept. of Pneumology-Allergology, Avenue de l'hopital, 13, 4000, Liege, Belgium.Dept. of Pneumology-AllergologyAvenue de l'hopital, 13Liege4000Belgium

Abstract

Background

Benralizumab is an anti-IL-5 receptor (IL-5R) therapy linked to a huge improvement of the condition of patients with severe eosinophilic asthma. The goal of this study was to identify baseline airway markers of remission and response after anti-IL5R therapy.

Methods

This observational study included 45 patients initiated with an anti-IL-5R. Remission was defined as: no oral corticosteroids intake, no exacerbation, a good asthma control (ACQ <1.5 and/or ACT >19) and a good lung function (FEV₁ ≥ 80 % predicted and/or an improvement ≥10 %). Components of remission were also assessed individually to evaluate the response of patients. Sputum levels of mediators implicated in inflammation and remodeling were measured before treatment.

Results

Among the 45 patients, 12 were classified in remission. These patients were younger at baseline, had a lower smoking exposure, better asthma control and quality of life and a higher FeNO compared to the others. Moreover, baseline blood eosinophil counts were similar but sputum IL-6 and IL-8 levels were significantly higher in the non-remission group. Finally, patients who only improved their ACT or ACQ score had higher baseline FeNO values or sputum eosinophil percentage respectively. Those who increased their FEV₁ ≥ 10 % presented a higher baseline sputum eosinophil percentage, sputum eotaxin-3 level and a trend for a higher sputum IL-5 level.

Conclusion

High baseline airway T2 markers appeared to be associated with response to anti-IL-5R therapy. Lower sputum IL-6 and IL-8 levels were linked to remission. These results need to be validated in a bigger cohort.

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Highlights

•	The study aims to find airway markers of remission/response after anti-IL5R.
•	Sputum mediators were measured using a sensitive ELISA method.
•	High baseline airway T2 markers are linked to remission/response after anti-IL-5R.

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Keywords : Asthma, Biotherapy, Remission, Sputum