Abstract
Rationale: We investigated whether benralizumab targeted IL-5Rα+ cells involved in eosinophilopoietic processes that drive airway eosinophilia in severe asthma.
Methods: In a Canadian substudy of ZONDA, 18 patients with severe, prednisone-dependent asthma received 28-week benralizumab 30 mg SC Q4W or Q8W (Q8W: first 3 doses every 4 weeks) or placebo (PBO) Q4W, after a steroid optimization phase (V4), followed by steroid taper (V14). Mature eosinophils, eosinophil-lineage committed progenitor cells (EoP), and IL-5Rα+ILC2s were enumerated by flow cytometry in blood and sputum. Protein granzyme B, tryptase, and relevant cytokines were examined in cell-free sputum supernatants. Outcomes for both regimens were combined (n=10) and compared with PBO (n=7). Data are medians and IQRs. Mann-Whitney U test compared changes with drug (V14–V6) vs. PBO (V14–V6).
Results: Benralizumab vs. PBO significantly reduced blood eos (0.24 [0.1–0.43] to 0.005 [0–0.013] vs. 0.4 [0.21–0.59] to 0.34 [0.26–0.57] x 106/ml; p<0.01) and sputum eosinophilia (2.8% [0.9–6.7] to 1.3% [0.15–1.3] vs. 3% [1.3–5] to 23.9% [9.3–32.5]; p<0.01). Drug treatment vs. PBO led to greater reductions in blood EoP (34 [8.7–77.9] to 0.6 [0.3–1.2] vs. 9.6 [0.8–22.8] to 0.9 [0.13–7.5]; p<0.05) and IL-5Rα+ILC2s (2.5 [0.3–15.3] to 0.3 [0.07–0.9] vs. 0.18 [0–1.0] to 0.7 [0.3–2.3] x 103 cells/ml; p<0.05). There was a trend for greater reduction in sputum ILC2 and EoP with benralizumab vs. PBO (p=0.2; p=0.24). Increased NK-cell cell activity was reflected by increases in granzyme B (p=0.02) and interferon-γ (p=0.03) with benralizumab vs. PBO.
Conclusions: Benralizumab 30 mg SC for 28 weeks attenuated systemic and airway eos, EoP, and IL5Rα+ILC2.
- Copyright ©the authors 2017