Soendergaard Marianne Baastrup, Hjortdahl Frederikke, Hansen Susanne, Bjerrum Anne-Sofie, von Bülow Anna, Hilberg Ole, Bonnesen Bertelsen Barbara, Johnsen Claus Rikard, Lock-Johansson Sofie, Vijdea Roxana, Rasmussen Linda Makowska, Schmid Johannes Martin, Ulrik Charlotte Suppli, Porsbjerg Celeste, Håkansson Kjell Erik Julius
Department of Respiratory Medicine, Copenhagen University Hospital - Bispebjerg, Copenhagen, Denmark.
M.B. Soendergaard and F. Hjortdahl contributed equally to this work.
Eur Respir J. 2025 Apr 3;65(4). doi: 10.1183/13993003.01497-2024. Print 2025 Apr.
Biologics can induce remission in some patients with severe asthma; however, little is known about pre-biologic disease trajectories and their association with outcomes from biological treatment. We aimed to identify long-term trajectories of disease progression in patients initiating biologics and investigate trajectory associations with disease burden and impact on biologic therapy efficacy.
Patients in the Danish Severe Asthma Register initiating biologic therapy between 2016 and 2022 were included and followed retrospectively in prescription databases starting 1995. We performed sequence analysis for inhaled corticosteroid treatment intensity over time combined with unsupervised trajectory clustering.
In total, 755 patients were included and three pre-biologic disease trajectories were identified: "Chronic severe asthma" (26%), "Gradual onset severe asthma" (35%) and "Recent, sudden onset severe asthma" (39%). "Chronic severe asthma" patients were older, had the longest disease duration (35 years), the most impaired pulmonary function, the highest comorbidity prevalence and the lowest employment rate. "Recent, sudden onset severe asthma" patients were younger, had shorter disease duration (5 years), more tobacco exposure and the least impaired lung function. "Gradual onset severe asthma" patients had an intermediate burden of disease. The Chronic severe asthma" cluster demonstrated the lowest prevalence of remission (17%) compared to the "Gradual onset severe asthma" (29%) and "Recent, sudden onset severe asthma" (32%) clusters.
Three pre-biologic disease trajectories were identified, with increased disease duration and activity associating with asthma and comorbidity burden. Early intervention may be key to prevent irreversible adverse outcomes for patients with severe asthma.
生物制剂可使部分重度哮喘患者病情缓解；然而，对于生物制剂治疗前的疾病轨迹及其与生物治疗结果的关联知之甚少。我们旨在确定开始使用生物制剂的患者疾病进展的长期轨迹，并研究轨迹与疾病负担的关联以及对生物治疗疗效的影响。
纳入丹麦重度哮喘登记处2016年至2022年间开始生物治疗的患者，并从1995年开始在处方数据库中进行回顾性随访。我们对吸入性糖皮质激素治疗强度随时间的变化进行序列分析，并结合无监督轨迹聚类。
共纳入755例患者，确定了三种生物制剂治疗前的疾病轨迹：“慢性重度哮喘”（26%）、“逐渐起病的重度哮喘”（35%）和“近期突发的重度哮喘”（39%）。“慢性重度哮喘”患者年龄较大，病程最长（35年），肺功能受损最严重，合并症患病率最高，就业率最低。“近期突发的重度哮喘”患者年龄较小，病程较短（5年），吸烟暴露更多，肺功能受损最轻。“逐渐起病的重度哮喘”患者的疾病负担处于中等水平。与“逐渐起病的重度哮喘”（29%）和“近期突发的重度哮喘”（32%）组相比，“慢性重度哮喘”组的缓解率最低（17%）。
确定了三种生物制剂治疗前的疾病轨迹，疾病持续时间和活动度增加与哮喘及合并症负担相关。早期干预可能是预防重度哮喘患者出现不可逆不良结局的关键。
