Efficacy and Safety of Benralizumab for Korean Patients With Severe, Uncontrolled Eosinophilic Asthma

PURPOSE: In the Phase III SIROCCO trial (NCT01928771), benralizumab significantly reduced asthma exacerbations and improved lung function and symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate efficacy and safety of benralizumab for Korean patients in SIROCCO. METHODS: SIROCCO was a randomized, double-blind, parallel-group, placebo-controlled trial of 1,204 patients aged 12–75 years with severe asthma uncontrolled by high-dosage inhaled corticosteroids/long-acting β2-agonists (ICS/LABA). Patients received benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W; first 3 doses Q4W) or placebo Q4W for 48 weeks. The primary analysis population comprised patients with blood eosinophil counts ≥ 300 cells/µL. This subgroup analysis evaluated Korean patients from this group. RESULTS: Of 122 Korean patients randomized, 86 had blood eosinophil counts ≥ 300 cells/µL. Benralizumab reduced the annual asthma exacerbation rate by 70% (Q4W: rate estimate 0.79, rate ratio 0.30 [95% confidence interval {CI}, 0.13–0.65], nominal P = 0.003; n = 28) and 85% (Q8W: rate estimate 0.40, rate ratio 0.15 [95% CI, 0.06–0.36], nominal P < 0.001; n = 30) vs. placebo (rate estimate 2.67, n = 28). Prebronchodilator forced expiratory volume in 1 second was increased with benralizumab treatment by 0.270 L (Q4W: 95% CI, 0.039–0.500, nominal P = 0.023; n = 28) and 0.362 L (Q8W: 95% CI, 0.143–0.582, nominal P = 0.002; n = 30) vs. placebo (n = 27). Total asthma symptom score was similar for patients receiving either benralizumab Q4W (−0.27 [95% CI, −0.83 to 0.30], nominal P = 0.356; n = 27) or benralizumab Q8W (0.10 [95% CI, −0.44 to 0.65], nominal P = 0.708; n = 30) vs. placebo (n = 28). Drug-related adverse events were experienced by 2%, 8%, and 5% of patients in the placebo, benralizumab Q4W, and benralizumab Q8W arms. CONCLUSIONS: Benralizumab reduced annual asthma exacerbation rates, increased lung function, and was well-tolerated by Korean patients with severe, uncontrolled eosinophilic asthma.

Effect of combined use of sIL-5Rα and sIL-13Rα2 on VCAM-1 and IFN-γ in allergic rhinitis rats / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of sIL-5Rα and sIL-13Rα2 on VCAM-1 and IFN-γ in allergic rhinitis rats.</p><p><b>METHODS</b>A total of 50 Wistar rats were randomly divided into 5 groups: the normal group (group A), the allergic rhinitis model group (group B), the sIL-5Rα treatment group (group C), the sIL-13Rα2 treatment group (group D), the combination of sIL-5Rα and sIL-13Rα2 treatment group (group E or the combined treatment group). Rats in the latter 4 groups were sensitized with ovalbumin (OVA) and Al(OH)(3), and challenged with OVA to establish allergic rhinitis models, while rats in the normal group were treated with saline. Rats in the sIL-5Rα treatment group, the sIL-13Rα2 treatment group and the combined treatment group were absorbed on day 31 to day 38 once daily once nasal cavity with sIL-5Rα(100 µg), sIL-13Rα2 (100 µg) and the combination of sIL-5Rα (100 µg) and sIL-13Rα2 (100 µg) 30 min before challenged, while rats in the allergic rhinitis model group received PBS(50 µl). Then the levels of VCAM-1 and IFN-γ in serum and nasal lavage fluid (NLF) were measured by ELISA.</p><p><b>RESULTS</b>Compared with the normal group, the levels of VCAM-1 in the allergic rhinitis model group were higher, while IFN-γ were lower (all P < 0.01). Compared with the allergic rhinitis model group, the sIL-5Rα treatment group, the sIL-13Rα2 treatment group and the combined treatment group could effectively reduced serum and NLF VCAM-1 level [group E: (283.5 ± 5.7) µg/L, (101.8 ± 4.8) µg/L; group C: (311.5 ± 12.6) µg/L, (133.9 ± 5.8) µg/L; group D: (304.7 ± 6.6) µg/L, (128.5 ± 7.7) µg/L], and increased IFN-γ level [group E: (874.7 ± 9.6) pg/ml, (349.2 ± 12.1) pg/ml; group C: (600.2 ± 16.1) pg/ml, (195.5 ± 16.1) pg/ml; group D: (577.9 ± 9.6) pg/ml, (196.7 ± 9.9) pg/ml ]; compared with single treatment, the combined treatment group also had significant differences(P < 0.01).</p><p><b>CONCLUSIONS</b>Combined treatment with sIL-5Rα and sIL-13Rα2 to treat the allergic rhinitis rats can significantly reduce VCAM-1 levels in serum and NLF, and increase IFN-γ levels, thus, to achieve the purpose of mitigation and treatment of allergic rhinitis.</p>

Relationship between bone marrow-derived CD34 + cells expressing interleukin-5 receptor messenger RNA and asthmatic airway inflammation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Asthma is clinically related with the degree of eosinophilic inflammation. How asthmatic airway inflammation is affected is still poorly understood. So the effects of bone marrow-derived hematopoietic cells expressing CD(34) (CD(34)(+)) and interleukin-5 (IL-5) receptor messenger RNA (IL-5R mRNA+) on asthmatic airway inflammation were investigated.</p><p><b>METHODS</b>Balb/c mice were sensitized and challenged by ovalbumin (OVA) to establish an asthmatic model while control mice were sensitized and exposed to sterile saline. The mice were killed at different time points after being challenged by OVA and sterile saline. Then, bronchoalveolar lavage fluid (BALF), peripheral blood (PB) and bone marrow (BM) were prepared. Eosinophils in PB (PBEOS) and BALF (BALFEOS), nuclear cells in BALF, PB and BM were counted. By flow cytometry, the percentage of CD(34)(+) cells to nucleated cells in PB, BM and the relative number of CD(34)(+) cells in PB (PBCD(34)(+)) and BM (BMCD(34)(+)) were calculated. Immunocytochemistry and in situ hybridization were used to investigate the hematopoietic cells with co-localized expression of CD(34) and IL-5R mRNA in BM (BMCD34+IL-5R mRNA+). The percentage of BMCD34+IL-5R mRNA+ to BMCD(34)(+) was calculated.</p><p><b>RESULTS</b>Twelve hours after challenge by OVA, BALFEOS and PBEOS in the experimental group were significantly higher than those in the control group (P < 0.01). Twenty-four hours after OVA challenge, BALFEOS, PBEOS and BMCD34+IL-5R mRNA+ were elevated maximally, significantly different from those in the control group (P < 0.01). Forty-eight hours after OVA challenge, BALFEOS and BMCD34+IL-5R mRNA+ were still significantly higher than those of the controls (P < 0.01). The other markers reverted to normal. In 60 mice, BMCD34+IL-5R mRNA+ was closely correlated with the BALEOS, PBEOS, BMCD(34)(+) and BMCD(34)(+) (%) (P < 0.05).</p><p><b>CONCLUSIONS</b>The amount of CD(34)(+) cells expressing IL-5R mRNA increased in the BM of asthmatic model mice, which favors eosinophilopoiesis and eosinophilic airway inflammation. A signal pathway exists between the lungs and the bone marrow, which is involved in the initiation and maintenance of asthmatic airway inflammation.</p>