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

Abstract

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. To investigate whether the response to anti-IL5/anti-IL5Rα therapies differs between patients with positive and negative BDR at baseline. Retrospective multicenter analysis of treatment outcomes in patients with severe asthma receiving anti-IL-5/anti-IL-5Rα stratified for baseline BDR. 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) andresidual 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. 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.