Overall Response to Anti-IL-5/Anti-IL5-Rα Treatment in Severe Asthma Does Not Depend on Initial Bronchodilator Responsiveness

Carlo Mümmler; Hendrik Suhling; Julia Walter; Nikolaus Kneidinger; Roland Buhl; Moritz Z Kayser; Nora Drick; Jürgen Behr; Tobias Welte; Stephanie Korn; Katrin Milger

doi:10.1016/j.jaip.2022.07.007

Overall Response to Anti-IL-5/Anti-IL5-Rα Treatment in Severe Asthma Does Not Depend on Initial Bronchodilator Responsiveness

J Allergy Clin Immunol Pract. 2022 Dec;10(12):3174-3183. doi: 10.1016/j.jaip.2022.07.007. Epub 2022 Jul 21.

Authors

Affiliations

¹ Department of Medicine V, University Hospital, LMU Munich, Germany; Comprehensive Pneumology Center (CPC-M), LMU and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
² Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
³ Department of Medicine V, University Hospital, LMU Munich, Germany.
⁴ Clinical Research Centre for Respiratory Medicine, Mainz, Germany.
⁵ Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
⁶ IKF Pneumologie Mainz, Mainz, Germany; Pneumology and Critical Care Medicine, Thoraxklinik Heidelberg, Heidelberg, Germany.
⁷ Department of Medicine V, University Hospital, LMU Munich, Germany; Comprehensive Pneumology Center (CPC-M), LMU and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany. Electronic address: Katrin.Milger@med.uni-muenchen.de.

PMID: 35870725
DOI: 10.1016/j.jaip.2022.07.007

Abstract

Background: Positive bronchodilator responsiveness (BDR) (change in forced expiratory volume in 1 second [ΔFEV₁] ≥ +200 mL and ≥ +12%) after inhalation of a short-acting beta-2 agonist has been an inclusion criterion in licensing trials of anti-interleukin 5/anti-interleukin 5 receptor alpha (anti-IL-5/anti-IL-5Rα) biologics in severe asthma. However, in clinical practice, patients with severe uncontrolled asthma frequently show a negative BDR.

Objective: To investigate whether the response to anti-IL5/anti-IL5Rα therapies differs between patients with positive and negative BDR at baseline.

Methods: Retrospective multicenter analysis of treatment outcomes in patients with severe asthma receiving anti-IL-5/anti-IL-5Rα stratified for baseline BDR.

Results: Of 133 patients included, 37 had a positive and 96 had a negative BDR at baseline. Following anti-IL-5/anti-IL-5Rα treatment, FEV₁ improved significantly in both groups compared with baseline (P < .0001), with no significant difference between patients with positive and negative BDR (ΔFEV₁ +493 mL vs +306 mL; P = .06). Forced vital capacity (FVC) increased (ΔFVC: +85 mL vs +650 mL; P < .01) and residual volume (RV) decreased (ΔRV +113 mL vs -307 mL; P < .01) significantly in patients with negative BDR. Median annualized exacerbations (0 vs 0; P = .7), reduction of exacerbation rate (Δexacerbations 0 vs -2; P = .07), continuous oral corticosteroids (OCS) use (Δpatients on OCS -35% vs -39%; P = .99) and improvement of Asthma Control Test (ACT) score (ΔACT 6 vs 5; P = .7) were similar in both groups. Multivariate logistic regression analysis showed no significant correlations of positive versus negative BDR with response parameters.

Conclusions: Both groups improved following treatment with similar responses concerning reduction of OCS therapy, exacerbations, and improvement of symptom control. Pulmonary function also improved in both groups during anti-IL-5/anti-IL-5Rα treatment, with differences in response patterns noted.

Keywords: Antibody; Benralizumab; Biologic; Bronchodilator responsiveness; Mepolizumab; Severe asthma.

Publication types

Multicenter Study

MeSH terms

Adrenal Cortex Hormones / therapeutic use
Asthma* / diagnosis
Bronchodilator Agents* / therapeutic use
Forced Expiratory Volume / physiology
Humans
Vital Capacity / physiology

Substances

Bronchodilator Agents
Adrenal Cortex Hormones