Abstract

Objective

Omalizumab is more effective in severe allergic patients with eosinophilic asthma than those with non-eosinophilic asthma. IL-18, a unique cytokine involved in allergic but non-eosinophilic inflammation, might be associated with the latter condition. We aimed to clarify the roles of IL-18 related pathways in insufficient response to omalizumab treatment.

Methods

Patients with severe allergic asthma who completed 2-year omalizumab treatments at Kyoto University Hospital were included in this study (UMIN000002389). Associations between pretreatment levels of serum free IL-18 in addition to other mediators and asthma phenotypes including responses to omalizumab treatment were analyzed. Changes in serum free IL-18, periostin and total IgE levels during the treatment were also examined.

Results

Twenty-seven patients (19 females, average age of 55.7 years) were examined. Fifteen incomplete responders who experienced exacerbations in the second year, were significantly and more frequently obese and showed significantly earlier asthma onset, lower blood eosinophils and more exacerbations before omalizumab treatment than complete responders. Significantly more patients showed high baseline serum free IL-18 levels (≥141 pg/mL, a threshold for the highest tertile) among the incomplete responders than complete responders. Patients with high serum free IL-18 levels shared similar characteristics with incomplete responders, showing significant reductions in serum total IgE levels during omalizumab treatment. Finally, serum free IL-18 levels negatively correlated with serum periostin levels at baseline and in change ratios.

Conclusions

High baseline serum free IL-18 levels may predict reduced omalizumab efficacy in severe allergic patients with type-2 low asthma, regarding reduction of exacerbations.

中文翻译：

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高血清游离 IL-18 与奥马珠单抗疗效降低有关：一项为期 2 年的奥马珠单抗治疗研究结果

摘要

客观的

与非嗜酸性粒细胞性哮喘患者相比，奥马珠单抗对嗜酸性粒细胞性哮喘的严重过敏患者更有效。IL-18 是一种参与过敏性但非嗜酸性炎症的独特细胞因子，可能与后一种情况有关。我们旨在阐明 IL-18 相关通路在对奥马珠单抗治疗反应不足中的作用。

方法

在京都大学医院完成了 2 年奥马珠单抗治疗的重度过敏性哮喘患者被纳入本研究 (UMIN000002389)。分析了除其他介质外，治疗前血清游离 IL-18 水平与哮喘表型（包括对奥马珠单抗治疗的反应）之间的关联。还检查了治疗期间血清游离 IL-18、骨膜蛋白和总 IgE 水平的变化。

结果

对 27 名患者（19 名女性，平均年龄 55.7 岁）进行了检查。在第二年经历恶化的 15 名不完全反应者明显且更频繁地肥胖，并且与完全反应者相比，在奥马珠单抗治疗前显示出明显更早的哮喘发作、更低的血嗜酸性粒细胞和更多的恶化。与完全反应者相比，不完全反应者中显着更多的患者显示出高基线血清游离 IL-18 水平（≥141 pg/mL，最高三分位数的阈值）。血清游离 IL-18 水平高的患者与不完全应答者具有相似的特征，在奥马珠单抗治疗期间血清总 IgE 水平显着降低。最后，血清游离 IL-18 水平与基线时的血清骨膜素水平和变化比率呈负相关。

结论

高基线血清游离 IL-18 水平可预测奥马珠单抗在 2 型低度哮喘严重过敏患者中的疗效降低，这与急性加重的减少有关。