Clinical Research Center, National Hospital Organization Tokyo National Hospital, Japan.
Department of Respiratory Medicine, The University of Tokyo, Japan.
Intern Med. 2024 Jan 15;63(2):179-187. doi: 10.2169/internalmedicine.1808-23. Epub 2023 May 24.
Objective Dupilumab, a monoclonal antibody specific for the human interleukin (IL)-4 receptor α, is used to treat severe asthma, especially in patients with elevated blood eosinophil counts and fractional exhaled nitric oxide (FeNO). The therapeutic response to dupilumab is highly variable. In this study, we explored new serum biomarkers to accurately predict the effect of dupilumab and examine the effect of dupilumab based on changes in the clinical parameters and cytokine levels. Methods Seventeen patients with severe asthma treated with dupilumab were enrolled. Responders, defined as those with a >0.5-point decrease in the Asthma Control Questionnaire (ACQ) score after 6 months of treatment, were included. Results There were 10 responders and 7 non-responders. Serum type 2 cytokines were equivalent between responders and non-responders; the baseline serum IL-18 level was significantly lower in responders than in non-responders (responders, 194.9±51.0 pg/mL; non-responders, 323.4±122.7 pg/mL, p=0.013). The cut-off value of IL-18 at 230.5 pg/mL could be used to distinguish non-responders from responders (sensitivity 71.4, specificity 80.0, p=0.032). Conclusion A low baseline serum IL-18 level may be a useful predictor of an unfavorable response to dupilumab in terms of the ACQ-6.
目的 度普利尤单抗是一种针对人白细胞介素(IL)-4 受体 α 的单克隆抗体,用于治疗严重哮喘,尤其是血嗜酸性粒细胞计数和呼出气一氧化氮(FeNO)升高的患者。度普利尤单抗的治疗反应差异很大。在这项研究中,我们探索了新的血清生物标志物来准确预测度普利尤单抗的疗效,并根据临床参数和细胞因子水平的变化来检查度普利尤单抗的疗效。
方法 纳入了 17 例接受度普利尤单抗治疗的严重哮喘患者。将治疗 6 个月后哮喘控制问卷(ACQ)评分降低≥0.5 分的患者定义为应答者。
结果 有 10 例应答者和 7 例无应答者。应答者和无应答者的血清 2 型细胞因子无差异;应答者的基线血清白细胞介素-18(IL-18)水平明显低于无应答者(应答者,194.9±51.0 pg/mL;无应答者,323.4±122.7 pg/mL,p=0.013)。IL-18 的截断值为 230.5 pg/mL 时,可以区分无应答者和应答者(灵敏度 71.4%,特异性 80.0%,p=0.032)。
结论 基线时血清 IL-18 水平较低可能是预测 ACQ-6 应答不良的一个有用指标。