Improving Eosinphilic Asthma with Reslizumab Add-On Treatment

Patients with late-onset eosinophilic asthma can potentially find relief with reslizumab (Cinqair/Teva Pharmaceuticals) humanized monoclonal antibody according to data from two 52-week long phase 3 trials. Results specifically showed that reslizumab reduces clinical asthma exacerbations (CAE) and improves lung functions in patients with inadequately controlled asthma.

Guy Brusselle, MD, PhD, (Photo), with Ghent University Hospital's Department of Respiratory medicine led the study, which aimed to determine the efficacy and safety of Reslizumab as an add-on therapy for patients with late-onset asthma (developing after 40 years of age).

The data for the analysis took place between April 2011 and April 2014. The original study, published in The Lancelet, was designed as a double blind, randomized, placebo-controlled phase 3 trial to determine safety and efficacy of reslizumab in a clinical population.

Enrolled participants were between the ages of 12 and 75 years old, had inadequately controlled asthma despite use of inhaled corticosteroids (ICS), and had high blood eosinophils. At the end of the original study, headed by Mario Castro, MD, with the Division of Pulmonary and Critical Care Medicine at the Washington University School of Medicine in St. Louis, MO, researchers determined that patients receiving reslizumab as an add-on therapy had a significant reduction in asthma exacerbations.

Using pooled data from the previous studies, Brusselle and colleagues focused on only those study participants whose first asthma onset occurred at 40 years or older. The team also explored data from other age sets for comparison's sake. Brusselle and colleagues found that of the 931 randomized patients included in their post-hoc analysis, patients with late onset asthma had a "higher background CAE rate" in the placebo group, even compared to the overall population of patients with late-onset asthma.

Those patients with late onset asthma receiving treatment with resilzumab saw a 75% reduction in CAE and in ER visits or hospitalizations due to CAE. This was a statistically significant reduction compared to the overall study population (34% reduction in ER visits and hospitalizations) and those patients with earlier onset of asthma (12% reduction in ER visits and hospitalizations).

Brusselle reported that "the larger magnitude of reslizumab benefit in reducing CAES in Patients with LO [late onset] asthma compared with the overall population and patients with early-onset asthma was consistently observed across a range of LO asthma age cut offs."

Reslizumab treatment also resulted in improvement in 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 LO asthma.

The study suggested that the difference in the magnitude of reslizumab treatment effects between patients with late onset vs. early onset asthma could indicate a "difference in the pathobiology between the overall eosinophilic asthma population and those with LO asthma." Brusselle and colleagues theorized that increased response to resilzumab might be related to "corticosteroid-resistant production of IL-5 by ILC2 cells," which creates inhaled corticosteroid resistance signaling in patients with late-onset asthma.

The study concluded that their discoveries increase understanding of eosinophilic asthma and could help identify "patients most likely to achieve a clinically meaningful response" to resilzumab treatment.

The article, “Reslizumab in Patients with Inadequately Controlled Late-Onset Asthma and Elevated Blood Eosinophils,” appears in the April 2017 issue of Pulmonary Pharmacology and Therapeutics.

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The Importance of Eosinophils in Personalized Severe Asthma Treatment