High serum cytokine levels may predict the responsiveness of patients with severe asthma to benralizumab

Abstract

Objective: Benralizumab, a humanized monoclonal antibody against human IL-5 receptor alpha, is effective in treating eosinophilic severe asthma. However, patients’ response to benralizumab varies widely. In this study, we aimed to identify a new serum biomarker to accurately predict benralizumab response.

Methods: Seventeen benralizumab-treated patients with severe eosinophilic asthma were enrolled. Blood samples were collected; pulmonary function tests were performed and questionnaires were disseminated at baseline and after 1, 2, 4, and 6 months of treatment. Blood cytokine levels were measured. Response was defined as an elevation in forced expiratory volume in 1 s of at least 10.4% from baseline after 4 months of treatment.

Results: There were nine respondents and eight non-respondents. The non-responders showed significantly higher baseline serum interferon-γ; interleukin (IL)-4, -5, -6, -7, and -12p70; IL-17/IL-17A; IL-17E/IL-25; IL-18/IL-1F4; chemokine (C-C motif) ligand (CCL)3/macrophage inflammatory protein (MIP)-1α; CCL4/MIP-1β; CCL11/eotaxin; matrix metalloproteinase-12; tumor necrosis factor-α, and thymic stromal lymphopoietin levels. After benralizumab administration, the serum CCL3/MIP-1α and CCL11/eotaxin levels significantly and persistently increased in the responders (CCL3/MIP-1α, responders: 144.5 ± 37.9 pg/ml (baseline) vs. 210.3 ± 59.4 pg/ml (4 months), p = 0.009; non-responders: 270.8 ± 139.8 pg/ml (baseline) vs. 299.5 ± 159.9 pg/ml (4 months), p = 0.33; CCL11/eotaxin, responders: 167.9 ± 62.6 pg/ml (baseline) vs. 326.7 ± 134.4 pg/ml (4 months), p = 0.038; non-responders: 420.9 ± 323.1 pg/ml (baseline) vs. 502.1 ± 406.0 pg/ml (4 months), p = 0.30).

Conclusion: Low baseline serum inflammatory cytokine levels may be useful in predicting a good benralizumab response.

Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Keywords:

• Benralizumab
• asthma
• eosinophils
• cytokine
• CCL11/eotaxin
• CCL3/MIP-1α

Acknowledgements

The authors thank Ms. Sayaka Igarashi for her skilled technical assistance. We also extend our gratitude to Mses. Mariko Yoshizawa and Taeko Kawabe for their excellent secretarial work.

Declaration of interest

Maho Suzukawa received research funding from Shionogi, MSD, Sanofi, Kyorin, AstraZeneca, and GlaxoSmithKline. The other authors have no conflicts of interest to disclose. Nobuharu Ohshima received honorarium from AstraZeneca, and GlaxoSmithKline.