BACKGROUND Interleukin (IL)-6 signalling has been implicated in allergic asthma by animal, genetic association and clinical studies. In this study, we tested the hypothesis that tocilizumab (TCZ), a human monoclonal antibody that blocks IL-6 signalling, can prevent the development of allergen-induced bronchoconstriction in humans. METHODS We performed a randomised, double-blind, placebo-controlled study, with eligible participants completing two allergen inhalation challenge tests, conducted before and after treatment with a single dose of TCZ or placebo. The primary efficacy endpoint was the magnitude of the late asthmatic response recorded between 3 and 7 after allergen challenge. The secondary efficacy endpoint was the early asthmatic response, measured 20 min to 2 h after allergen challenge. RESULTS A total of 66 patients enrolled between September 2014 and August 2017, when the trial was stopped for futility based on results from an interim analysis. Eleven patients fulfilled all eligibility criteria assessed at baseline and were subsequently randomised to the TCZ (n = 6) or placebo (n = 5) groups. Both the primary and secondary efficacy endpoints were not significantly different between the two groups. Five patients reported adverse events (AEs), three in the TCZ group (11 AEs) and two in the placebo group (four AEs). Only one AE was TCZ-related (mild neutropenia), and there were no serious AEs. Significant treatment effects were observed for serum levels of C-reactive protein, IL-6 and soluble IL-6R levels. CONCLUSION In a small proof-of-concept clinical trial, we found no evidence that a single dose of tocilizumab was able to prevent allergen-induced bronchoconstriction. (Trial registered in the Australian New Zealand Clinical Trials Registry, number ACTRN12614000123640).

中文翻译：

---

白细胞介素 6 受体阻断对轻度哮喘患者过敏原诱导的气道反应的影响。

背景通过动物、遗传关联和临床研究，白细胞介素(IL)-6信号传导与过敏性哮喘有关。在这项研究中，我们检验了一种假设，即阻断 IL-6 信号传导的人单克隆抗体托珠单抗 (TCZ) 可以防止人类发生过敏原诱导的支气管收缩。方法 我们进行了一项随机、双盲、安慰剂对照研究，符合条件的参与者在单剂量 TCZ 或安慰剂治疗前后完成了两次过敏原吸入挑战试验。主要疗效终点是过敏原攻击后 3 至 7 日记录的晚期哮喘反应的幅度。次要疗效终点是早期哮喘反应，在过敏原攻击后 20 分钟至 2 小时测量。结果 2014 年 9 月至 2017 年 8 月期间共有 66 名患者入组，当时根据中期分析结果，试验因无效而停止。11 名患者符合基线评估的所有资格标准，随后被随机分配到 TCZ (n = 6) 或安慰剂 (n = 5) 组。两组的主要和次要疗效终点均无显着差异。5 名患者报告了不良事件 (AE)，TCZ 组 3 名 (11 AE) 和安慰剂组 2 名 (4 AE)。只有 1 个 AE 与 TCZ 相关（轻度中性粒细胞减少症），没有严重的 AE。观察到对血清 C 反应蛋白水平、IL-6 和可溶性 IL-6R 水平的显着治疗效果。结论 在一项小型概念验证临床试验中，我们没有发现任何证据表明单剂量的托珠单抗能够预防过敏原引起的支气管收缩。（在澳大利亚新西兰临床试验注册中心注册的试验，编号 ACTRN12614000123640）。