Baseline Cytokine Levels May Predict Patients’ Response to Benralizumab in Severe Asthma

woman using asthma inhaler
Woman using an inhaler for asthma
In a small Japanese study published in the Journal of Asthma, patients with severe asthma with low baseline cytokine levels responded well to benralizumab therapy.

Low baseline serum levels of inflammatory cytokines in patients with severe asthma may predict a favorable response to the monoclonal antibody benralizumab, a study in the Journal of Asthma suggests.

The study included 17 patients with severe eosinophilic asthma who received benralizumab at a single Tokyo hospital between 2018 and 2019. Benralizumab 30 mg was administered via subcutaneous injection at baseline, at 1 and 2 months, and every 8 weeks thereafter.

Investigators collected blood samples, conducted pulmonary function tests, and administered questionnaires at baseline and after 1, 2, 4, and 6 months. In addition, the investigators measured blood cytokine levels in serum samples at each follow-up period.

Response to therapy was defined in this study as an increase in forced expiratory volume in 1 second of at least 10.4% from baseline to 4 months after treatment.

At 4 months, the investigators identified 9 patients who responded to benralizumab therapy. Of the 8 patients who did not respond, the investigators found that at baseline these patients had significantly higher levels of 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; tumor necrosis factor-α; matrix metalloproteinase-12; and thymic stromal lymphopoietin.

Among the 9 responders, treatment with benralizumab resulted in significant increases in CCL3/MIP-1α from baseline to 4 months (144.5±37.9 pg/mL vs 210.3±59.4 pg/mL, respectively; P =.009). In contrast, the 8 nonresponders did not show a significant increase in CCL3/MIP-1α after benralizumab (270.8±139.8 pg/mL vs 299.5 ± 159.9 pg/mL; P =.33).

Responders also had a significant increase in CCL11/eotaxin over the treatment period (167.9±62.6 pg/mL vs 326.7±134.4 pg/mL; P =.038); nonresponders showed no significant increase (420.9±323.1 pg/mL vs 502.1±406.0 pg/mL; P =.30).

Limitations of this study included its small sample size, single-center design, and reliance on a single criterion to define treatment response.

Although this study suggests baseline cytokine levels may predict response to benralizumab, the researchers noted that larger trials “are necessary to support our results for the establishment of useful biomarkers for benralizumab therapy in patients with severe asthma.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Watanabe S, Suzukawa M, Tashimo H, et al. High serum cytokine levels may predict the responsiveness of patients with severe asthma to benralizumab. J Asthma. Published online July 1, 2021. doi:10.1080/02770903.2021.1942039