Hamada Yuto, Thomas Dennis, Harvey Erin S, Stevens Sean, Fricker Michael, Lewthwaite Hayley, McDonald Vanessa M, Gillman Andrew, Hew Mark, Kritikos Vicky, Upham John W, Gibson Peter G
Centre of Excellence in Treatable Traits, College of Health, Medicine and Wellbeing, The University of Newcastle, New Lambton Heights, Australia.
Asthma and Breathing Research Program, The University of Newcastle, New Lambton Heights, Australia.
Eur Respir J. 2025 Jan 30;65(1). doi: 10.1183/13993003.00782-2024. Print 2025 Jan.
Patients with severe eosinophilic asthma, characterised by a high disease burden, benefit from mepolizumab, which improves symptoms and reduces exacerbations, potentially leading to clinical remission in a subgroup. This study aimed to identify treatment response trajectories to mepolizumab for severe eosinophilic asthma and to assess the achievement of clinical remission.
Data from the Australian Mepolizumab Registry were used to assess treatment responses at 3, 6 and 12 months. The treatment response trajectories were identified using a group-based trajectory model. The proportions achieving clinical remission at 12 months, which was defined as well-controlled symptoms, no exacerbations and no oral corticosteroid (OCS) use for asthma management, were compared between trajectories, and baseline predictors of the trajectories were identified using logistic regression analysis.
We identified three trajectory groups: Group 1, "Responsive asthma with less OCS use" (n=170); Group 2, "Responsive late-onset asthma" (n=58); and Group 3, "Obstructed and less responsive asthma" (n=70). Groups 1 and 2 demonstrated higher proportions achieving clinical remission at 36.5% and 25.9%, respectively, compared to Group 3 with 5.7% (p<0.001). Baseline predictors for assigned groups included lower OCS dose in Group 1; greater forced expiratory volume in 1 s percentage predicted, higher Asthma Quality of Life Questionnaire score, higher OCS dose and nasal polyps in Group 2; with Group 3 as the reference.
Treatment response to mepolizumab in severe eosinophilic asthma follows three trajectories with varying proportions achieving clinical remission and differing baseline characteristics. Treatment response variability may influence the achievement of clinical remission with mepolizumab therapy.
重度嗜酸性粒细胞性哮喘患者疾病负担高，美泊利珠单抗对其有益，可改善症状并减少急性加重，在亚组患者中可能实现临床缓解。本研究旨在确定重度嗜酸性粒细胞性哮喘患者对美泊利珠单抗的治疗反应轨迹，并评估临床缓解的实现情况。
使用澳大利亚美泊利珠单抗注册研究的数据评估3、6和12个月时的治疗反应。使用基于组的轨迹模型确定治疗反应轨迹。比较各轨迹组在12个月时实现临床缓解（定义为症状得到良好控制、无急性加重且未使用口服糖皮质激素（OCS）治疗哮喘）的比例，并使用逻辑回归分析确定轨迹的基线预测因素。
我们确定了三个轨迹组：第1组，“使用较少OCS的反应性哮喘”（n = 170）；第2组，“反应性迟发性哮喘”（n = 58）；第3组，“阻塞性且反应性较低的哮喘”（n = 70）。第1组和第2组在12个月时实现临床缓解的比例分别为36.5%和25.9%，高于第3组的5.7%（p<0.001）。各分组的基线预测因素包括：第1组OCS剂量较低；第2组1秒用力呼气容积占预计值百分比更高、哮喘生活质量问卷得分更高、OCS剂量更高且有鼻息肉；以第3组作为对照。
重度嗜酸性粒细胞性哮喘患者对美泊利珠单抗的治疗反应遵循三种轨迹，实现临床缓解的比例不同，基线特征也不同。治疗反应的变异性可能会影响美泊利珠单抗治疗实现临床缓解的情况。
