Are Anti-IL5/Anti-IL5Rα Biologics Effective in Severe Asthma With Negative BDR?

Asian woman using a pressurized cartridge inhaler extended pharynx, Bronchodilator
How do patients with severe asthma and a negative bronchodilator response react to anti-IL5/anti-IL5α biologic therapies?

Patients with severe asthma undergoing treatment with anti-interleukin 5 (IL5)/anti-IL5 receptor α (IL5Rα) biologics experience improvements in oral corticosteroid use, exacerbations, and symptoms, regardless of whether they have positive vs negative bronchodilator responsiveness (BDR) prior to treatment, according to study findings published in the Journal of Allergy and Clinical Immunology: In Practice.

Although positive BDR has been a standard inclusion criterion in anti-IL5/anti-IL5Rα licensing trials, real-world patients with severe asthma often show a negative BDR. Researchers therefore sought to explore whether the response to anti-IL5/anti-IL5α therapies differs in patients with severe asthma among those with positive vs negative BDR at baseline.

The investigators conducted a retrospective, multicenter analysis of patients with severe asthma receiving anti-IL5/anti-IL5Rα biologics (ie, mepolizumab and benralizumab) who were included in the German Asthma Net (GAN) Severe Asthma Registry, which prospectively collects routine clinical parameters from patients with severe asthma at baseline and at annual follow-up visits. A total of 133 patients with BDR data available prior to anti-IL-5 or anti-IL5Rα therapy for at least 1 year were included in the study (60% females; mean age, 59 years; mean body mass index, 26 kg/m2). A positive BDR was defined as an increase in forced expiratory volume in 1 second (FEV1) of at least 200 mL and at least 12% following inhalation of short-acting beta2-sympathomimetics (SABAs).

Among the study participants, 37 had a positive BDR and 96 had a negative BDR at baseline. After anti-IL5/anti-IL5Rα treatment, significant improvements in FEV1 were reported in both groups, compared with baseline (P <.0001), with no significant difference observed between those with positive BDR and those with negative BDR
(difference in FEV1: 493 mL vs 306 mL, respectively; P =.06). Additionally, forced vital capacity (FVC) increased significantly (difference in FVC: 85 mL vs 650 mL; P <.01) and residual volume (RV) decreased significantly (difference in RV: 113 mL vs –307 mL; P <.01) in participants with negative BDR.

Median annualized exacerbations, reduction in exacerbation rate, continuous oral corticosteroid (OCS) use, and improvement in asthma control test (ACT) score were similar in patients with positive and negative BDR. Per multivariate logistic regression analysis, no significant correlations were reported with positive vs negative BDR and response parameters.

Limitations of the current study include its retrospective design and the real-life setting used for BDR testing. Additionally, although the participants were advised to stop inhalation and other interfering therapies prior to BDR testing, it is uncertain whether all participants were able to do this.

“In sum, we conclude that the pre-treatment BDR does not predict overall therapeutic benefit of the IL5 and IL5Rα antibodies mepolizumab and benralizuma,” said study authors. However, they did acknowledge observing “different patterns of [pulmonary function test] response under anti-IL5/anti-IL5Rα therapy, with predominant volume increases in BDR negative patients and predominant flow increases in BDR positive patients.” Study findings also suggest that “BDR should not be a criterion for withholding antibody treatment from patients with severe asthma,” and that there is a need to reevaluate “the current flow-related BDR definition as an inclusion criterion for severe asthma trials,” said study authors.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Mümmler C, Suhling H, Walter J, et al. Overall response to anti-IL5/anti-IL5Rα treatment in severe asthma does not depend on initial bronchodilator responsiveness. J Allergy Clin Immunol Pract. Published online July 20, 2022. doi:10.1016/j.jaip.2022.07.007