Severe Eosinophilic Asthma Linked to Low FEV1 Reversibility

In patients with inadequately controlled eosinophilic asthma, lung function and patient-reported improved outcomes with reslizumab—a humanized anti-interleukin-5 monoclonal antibody—improves asthma exacerbation rates.

In a phase 3 double blind, randomized, placebo-controlled clinical trial presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2019 Annual Meeting in San Francisco, CA, this week, investigators reported that patients with late-onset asthma receiving treatment with resilzumab had a 75% reduction in exacerbations and in hospitalizations due to exacerbations.

This was a statistically significant reduction compared to the overall study population (34% reduction in emergency room [ER] visits and hospitalizations) and those patients with earlier onset of asthma (12% reduction in ER visits and hospitalizations).

In addition, reslizumab treatment resulted in improvement in forced expiratory volume over 1 second (FEV₁) and improvements in asthma control and quality of life via patient-reported Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ6), and Asthma Symptom Utility Index (ASUI). Although there were improvements in these areas among all patients treated with reslizumab, the results were most significant for those with late-onset asthma.

Due to the knowledge that exists between reslizumab and eosinophilic asthma, investigators conducted a post-hoc analysis in order to assess EOS levels and lung function among patients with low FEV₁ reversibility (REV) to short-acting beta agonists (SABA).

In their analysis, the team used data from patients with screening EOS ≥400μL and REV ≥12% to SABA. Specifically, the data were pooled from a pair of 52-week placebo-controlled trials of intravenous (IV) reslizumab 3mg/kg (Q4wks) from these patients.

In the lowest-REV/highest-eosinophil (EOS) group, REV by baseline (day of first dose) EOS category and lung function treatment effect were analyzed.

The categorization of patients was conducted by baseline EOS <150 (n= 65), 150—<400 (n= 179), 400–<700 (n= 365), and ≥700/μL (n= 344) and by baseline REV <14% (n= 149), 14–<20% (n= 276), and ≥20% (n= 528).

Trends towards lower mean REV and a higher proportion with REV <14% were seen in patients with higher EOS levels, compared to patients with lower EOS levels.

FEV₁ 168mL (95% CI: 4—332), predicted FEV₁ 6.2% (1.1—11.2), FVC 144mL (-62–350), and FEV_25—75% 131mL (-96—357) included the treatment effects at 52 weeks (reslizumab vs placebo) in the low REV (<14%) group, which pooled the 2 highest EOS categories (≥700, 400–<700).

From their results, investigators concluded that in inadequately controlled eosinophilic asthma, higher blood EOS is associated with lower FEV₁ REV. They also concluded that in patients with high EOS and low REV, reslizumab treatment results in clinically significant improvements in lung function outcomes.

Additionally, reslizumab may relatively counteract fixed airway obstruction in these patients.

The study, titled, “High Peripheral Blood Eosinophil (EOS) Levels Are Associated With Low FEV₁ Reversibility (REV) In Patients With Severe Eosinophilic Asthma,” was published online in The Journal of Allergy and Clinical Immunology.