Investigators Find Predictors for Biologic Failure for Severe Eosinophilic Asthma

May 18, 2020
Kenny Walter

Kenny Walter is an editor with HCPLive. Prior to joining MJH Life Sciences in 2019, he worked as a digital reporter covering nanotechnology, life sciences, material science and more with R&D Magazine. He graduated with a degree in journalism from Temple University in 2008 and began his career as a local reporter for a chain of weekly newspapers based on the Jersey shore. When not working, he enjoys going to the beach and enjoying the shore in the summer and watching North Carolina Tar Heel basketball in the winter.

New research show younger age is associated with a non-response to biologic agents.

New biologic agents have improved the management of severe eosinophilic asthma in recent years, but clinically, researchers have observed a heterogeneous response to these therapies, resulting in the occasional need to transition to alternative biologic therapies.

In a new study planned to be presented at the American Thoracic Society (ATS) 2020 International Conference a team led by Reihman, Division of Pulmonary Sciences and Critical Care Medicine at the University of Colorado, examined why some patients do not response to interleukin 5 (IL-5)-targeting monoclonal antibodies.

In the new trial, the investigators examined 42 patients, 32 of which were classified as responders (76%) and 10 of which were categorized as non-responders (24%). Each patient was treated in the University of Colorado’s Severe Asthma Program from 2016-2019 with a clinical diagnosis of severe eosinophilic asthma and 1 or more follow-up clinic visits within 1 year after initiation of biologic therapy.

Patients were considered responders if they continued initial prescribed biologic agent or switch their biologic for a non-clinical reason. Non-responders were defined at participant whose biologic agent were switched because of worsened asthma, worsened sinus symptoms, or side effects caused by the medication.

The investigators performed a subgroup analysis in the subset of patients who failed an anti-IL5 antibody to identify the clinical predictors of treatment failure.

The investigators also tested for differences between responders and non-responders using the Mann-Whitney U and Fisher’s exact test.

In the non-responders group, half failed mepolizumab, while 30% failed reslizumab and 20% failed benralizumab.

The investigators did not find significant differences between the responder and non-responder groups based on sex, smoking status, body mass index, baseline pulmonary function, asthma control test score, fractional excretion of nitric oxide, peripheral eosinophil count, or immunoglobulin E levels.

In the subgroup analysis, the investigators found younger age was associated with mepolizumab and reslizumab (n = 16) biologic failure in non-responders compared to responders (mean age 55 vs 62 years; P <0.05). Non-responders also had an increased number of exacerbations the year prior to biologic therapy initiation (P <0.05).

“In this preliminary analysis, we found one quarter of severe asthmatics initiated on biologic therapy failed treatment and required switch to an alternative biologic agent. 80% of non-responders exhibited treatment failure to an anti-IL5 monoclonal antibody (mepolizumab or reslizumab),” the authors wrote. “Future evaluation of a larger cohort of patients and further investigation of additional biomarkers will allow us to further investigate clinical and molecular predictors for anti-IL5 treatment failure.”

In September, the US Food and Drug Administration approved mepolizumab as the first biologic indicated for children between 6-11 years old with severe eosinophilic asthma.

The 40 mg subcutaneous injection therapy was previously approved as an add-on maintenance drug for patients with severe eosinophilic asthma aged 12 years and older. Its emphasis on the prevention of eosinophil-binding has been shown to reduce eosinophil counts in patients without completing depleting them.

The study, “Clinical Predictors of Treatment Failure to Anti-IL5 Therapy in Severe Eosinophilic Asthma Add to Itinerary,” was published online by the ATS International Conference.