Study Compares Mepolizumab, Benralizumab for Eosinophilic Asthma

Mepolizumab and benralizumab are both potent targets of the interlukin-5 (IL-5) pathway with the ability to significantly reduce eosinophil counts, according to new research published in Allergy, Asthma & Clinical Immunology. Although no statistical difference in the magnitude of eosinophil reduction offered by each agent was found, researchers noted “benralizumab is able to decrease peripheral eosinophil counts to 0 cells/µL in more patients than mepolizumab.”

Type 2 asthma, or eosinophilic asthma, is a helper T cell 2 (Th2)–mediated process characterized by high blood and sputum eosinophil count. Canadian patients with eosinophilic asthma can currently choose from 4 targeted monoclonal antibodies approved by Health Canada, including mepolizumab and reslizumab, which target IL-5, and benralizumab, which targets the IL-5 receptor alpha (IL-5Rα) subunit.

“All IL-5 therapies have been shown to reduce oral corticosteroid use and overall asthma exacerbations,” the authors explained. But because benralizumab has a unique ability to deplete eosinophils compared with direct IL-5 antibodies, it is unclear whether it has clinical superiority.

Specifically, benralizumab acts by binding to the IL-5Rα subunit on eosinophils, which “not only prevents signal transduction but also triggers cell-mediated killing by the innate immune system resulting in eosinophil depletion.”

Because of its role in eosinophil activation, maturation, and survival, IL-5 has been a focus of treatment research for severe eosinophilic asthma for years. However, “Current Global Initiative for Asthma clinical guidelines released in 2019 do not provide guidance on selecting the various IL-5 treatment options.”

To determine if the peripheral eosinophil reduction efficacy of mepolizumab and benralizumab differ, researchers conducted a retrospective chart review of Canadian patients with severe eosinophilic asthma who were approved for either treatment.

All participants presented to a single center in Kitchener, Ontario, and any patients with noted nonadherence or who were on fluctuating doses of corticosteroids for non–asthma-related illness were excluded from the review.

Investigators compared pretreatment baseline eosinophil counts with posttreatment counts, defined as the highest count recorded after therapy start date with at least 30 days of adherence.

Over the course of the study window, 5 participants switched from mepolizumab to benralizumab due to inadequate control of asthma or intolerance to the therapy, whereas no participants switched from benralizumab to mepolizumab.

A total of 36 patients taking mepolizumab and 19 patients taking benralizumab were included in final analyses. No statistically significant differences between age, sex, smoking history, mean number of comorbidities, or additional compounding factors were found.

Analyses revealed:

• The mean pretherapy serum eosinophil count did not statistically differ between patients on mepolizumab (597.2 cells/mcL) compared with benralizumab (521.6 cells/mcL) (P = .376).
• The percentage of patients with eosinophilia (≥ 500 cells/mcL) prior to therapy onset was similar between groups (P = .273).
• Both therapies resulted in a significant decrease in eosinophil count (P < .0001) but the mean decrease did not statistically differ between patients taking mepolizumab and those taking benralizumab (P = .90).
• All patients with eosinophilia prior to therapy onset had posttherapy eosinophil counts within normal limits (< 500 cells/mcL).
• 100% of patients receiving benralizumab had undetectable eosinophil counts post therapy compared with 31% of patients receiving mepolizumab (P < .0001).

Two patients in the mepolizumab group exhibited elevations in their serum eosinophil count post therapy, with counts increasing from 200/cells mcL to 300 cells/mcL.

A small sample size and selection bias mark limitations to this study, and the retrospective nature of the study precludes understanding differences in potential confounders that were not measured.

In addition, “correlation of eosinophil depletion with clinical outcomes, such as measures of asthma control, effect on asthma exacerbation rates, changes in [forced expiratory volume in 1 second], or other biomarkers of asthma control—such as sputum eosinophil count or fractional exhaled nitric oxide—was not possible as the timing of the measurement of these clinical outcomes post-therapy onset was highly variable between patients, if these measurements were even available,” researchers noted.

Future studies ought to further evaluate the clinical significance of the noted difference found in this study, they concluded.

Reference

Ghassemian A, Park JJ, Tsoulis MW, and Kim H. Targeting the IL-5 pathway in eosinophilic asthma: a comparison of mepolizumab to benralizumab in the reduction of peripheral eosinophil counts. Allergy Asthma Clin Immunol. Published online January 6, 2021. doi:10.1186/s13223-020-00507-0