美国天普大学Gerard J. Criner领导的一个国际研究团队，评估了白细胞介素-5受体α定向细胞溶解单克隆抗体Benralizumab预防中重度慢性阻塞性肺疾病（COPD）患者病情恶化的疗效和安全性。相关论文2019年9月12日发表在《新英格兰医学杂志》上。

在GALATHEA和TERRANOVA试验中，研究人员招募了COPD患者（嗜酸性粒细胞计数大于和小于220/mm³的比率约为2：1），虽然根据指南接受了吸入治疗，但仍经常恶化。患者被随机分配到每8周（前三次每4周给药）接受一次Benralizumab（GALATHEA试验中剂量分别为30或100 mg，TERRANOVA试验中剂量分别为10、30或100 mg）或安慰剂治疗。

在GALATHEA试验中，30 mg Benralizumab组的年恶化率估计值为1.19/年，100 mg Benralizumab组为1.03/年，与安慰剂组相比（1.24/年），比率分别为0.96和0.83。在TERRANOVA试验中，10 mg、30 mg和100 mg Benralizumab组和安慰剂组的年恶化率分别为0.99/年、1.21/年、1.09/年和1.17/年，相应的比率分别为0.85、1.04和0.93。而在第56周时，两个试验中任何剂量Benralizumab的年化COPD恶化率均不优于安慰剂组。Benralizumab组和安慰剂组中不良反应的类型和频率均无统计学差异。

研究显示，对于中重度COPD患者，伴有频繁的恶化史，血嗜酸性粒细胞计数超过220/mm³的患者，使用Benralizumab治疗与安慰剂相比并不能显著降低恶化率。

附：英文原文

Title: Benralizumab for the Prevention of COPD Exacerbations

Author: Gerard J. Criner, M.D., Bartolome R. Celli, M.D., Christopher E. Brightling, M.D., Alvar Agusti, M.D., Ph.D., Alberto Papi, M.D., Dave Singh, M.D., Don D. Sin, M.D., Claus F. Vogelmeier, M.D., Frank C. Sciurba, M.D., Mona Bafadhel, M.D., Vibeke Backer, M.D., Motokazu Kato, M.D., Ph.D., et al., for the GALATHEA and TERRANOVA Study Investigators*

Issue&Volume: Vol 381 No 11

Abstract: 

BACKGROUND
The efficacy and safety of benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.

METHODS
In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment. Patients were randomly assigned to receive benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) every 8 weeks (every 4 weeks for the first three doses) or placebo. The primary end point was the treatment effect of benralizumab, measured as the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56 in patients with baseline blood eosinophil counts of 220 per cubic millimeter or greater. Safety was also assessed.

RESULTS
In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P=0.65) and 0.83 for 100 mg of benralizumab (P=0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P=0.06), 1.04 (P=0.66), and 0.93 (P=0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.

CONCLUSIONS
Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916. opens in new tab and NCT02155660. opens in new tab.)

DOI: 10.1056/NEJMoa1905248

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1905248