[A clinical observational study on the preliminary effect of dupilumab in the treatment of severe asthma].

Objective: To investigate the effect and safety of dupilumab in the treatment of patients with severe asthma in a preliminary clinical observational study. Methods: This study retrospectively analyzed the clinical data of 20 patients with severe asthma who received dupilumab for 4-12 months between 2019 and 2022 at the First Hospital of Guangzhou Medical University, comparing pre-and post-treatment laboratory data, oral glucocorticoid dose (OCS), asthma control test (ACT) and adverse effects. The median age of the 20 patients was 48.5 (41.0-52.8) years, including 14 males and 6 females. The clinical data of 10 patients treated with other biologic agents were further analyzed to determine the reasons for switching to biologic drug treatment and the efficacy of dupilumab in these patients. Paired t-tests or Wilcoxon signed-rank tests were used for comparisons. Mann-Whitney analysis was used for inter-group comparison, and chi-square test or Fisher test was used for inter-group comparisons of count data. Results: A total of 20 patients were included in this study. All 20 severe asthma phenotypes were type 2 (T2)-high and completed at least the first 4 months of treatment, including 17 patients who completed 12 months of treatment. Among patients who completed 4 months of treatment, the asthma exacerbation score decreased from 1.0(0.3-1.0) episodes/4 months to 0.0(0.0-1.0) episodes/4 months, P<0.001, and FEV1/FVC increased from 58.4% (50.5%-69.0%) to 66.9% (59.6%-77.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 15 (75%) to 9 (45%), P<0.05. Among patients who completed 12 months of treatment, the asthma exacerbation score decreased from 1.0(0.5-1.0) episodes/4 months to 0.0 (0.0-0.0) episodes/4 months, P<0.01, and FEV1/FVC increased from 57.9% (49.6%-67.8%) to 72.7% (64.6%-78.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 13 (76%) to 6 (35%), P<0.01. In 10 patients with a history of previous biologic therapy, the most common reasons for switching to a biologic were a poor response to previous monoclonal antibodies (40%) and loss of control of asthma symptom control after discontinuation of monoclonal antibodies (30%). The remaining reasons were patients' uncontrolled symptoms of chronic rhinosinusitis (20%) and irregular or underdosed use of previous biologics (10%). After 4 months of switching to dupilumab, 10 patients experienced varying degrees of improvement in asthma control. Conclusions: The application of dupilumab for the treatment of T2-high severe asthma showed good efficacy and few adverse effects. Biologically targeted therapy is an important treatment approach to achieving better control of severe asthma.目的： 初步观察度普利尤单抗治疗重度哮喘患者的有效性及安全性。 方法： 回顾性分析广州医科大学附属第一医院于2019—2022年接受度普利尤单抗治疗4~12个月的20例重度哮喘患者的临床资料，其中男14例，女6例，中位年龄48.5（41.0，52.8）岁。对比分析其治疗前后支气管哮喘症状控制评分（ACT）、实验室数据、口服糖皮质激素（OCS）剂量以及不良反应等数据，对10例曾使用其他生物制剂治疗的患者进一步研究，分析更换生物制剂的原因及度普利尤单抗对其疗效。两两前后比较采用配对t检验或非参数配对Wilcoxon分析，组间比较用非参数独立样本 Mann-Whitney分析，计数资料组间比较采用卡方检验或 Fisher检验分析。 结果： 共20例患者纳入本研究，均为2型炎症表型且至少接受前4个月治疗，其中17例完成12个月治疗。完成4个月治疗后，对比基线，哮喘急性发作次数由1.0（0.3，1.0）次/4个月降至0.0（0.0，1.0）次/4个月，P<0.001；FEV1/FVC由58.4%（50.5%，69.0%）升至66.9%（59.6%，77.7%），P<0.01；需OCS维持治疗的患者由15例（75%）降至9例（45%），P<0.05。完成12个月治疗后，对比基线，哮喘急性发作次数由1.0（0.5，1.0）次/4个月降至0.0（0.0，0.0）次/4个月，P<0.01；FEV1/FVC由57.9%（49.6%，67.8%）升至72.7%（64.6%，78.7%），P<0.01；需OCS维持治疗由13例（76%）降至6例（35%），P<0.01。对10例有生物制剂治疗史的患者分析，发现导致其更换生物制剂最多的原因是对单抗应答不佳（40%）以及停用单抗后哮喘失去控制（30%），其余原因是慢性鼻-鼻窦炎无法控制（20%）以及生物制剂不足剂量使用（10%），10例患者更换为度普利尤单抗4个月后哮喘控制水平有不同程度提升。 结论： 应用度普利尤单抗治疗2型炎症表型的重度哮喘，初步观察疗效良好，不良反应少。生物靶向治疗是使重度哮喘得到良好控制的重要手段。.