Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, NSW, Australia; School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia; Asthma and Breathing Research Centre, Hunter Medical Research Institute, Newcastle, NSW, Australia.
Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, NSW, Australia; School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia; Asthma and Breathing Research Centre, Hunter Medical Research Institute, Newcastle, NSW, Australia.
Ann Allergy Asthma Immunol. 2022 Aug;129(2):150-159. doi: 10.1016/j.anai.2022.04.020. Epub 2022 Apr 27.
T2-low asthma is an often severe asthma subtype with limited treatment options and biologic therapeutics are lacking. Several monoclonal antibodies (mAbs) targeting non-T2 cytokines were previously reported to be ineffective in asthma. These trials often investigated heterogeneous asthma populations and negative outcomes could be related to unsuitable study cohorts. More tailored approaches in selecting participants based on specific biomarkers have been beneficial in treating severe T2-high asthma. Similarly, mAbs previously deemed ineffective bear the potential to be useful when administered to the correct target population. Here, we review individual clinical trials conducted between 2005 and 2021 and assess the suitability of the selected cohorts, whether study end points were met, and whether outcome measures were appropriate to investigate the effectiveness of the respective drug. We discuss potential target groups within the T2-low asthma population and suggest biomarkers that may predict a treatment response. Furthermore, we assess whether biomarker-guided approaches or subgroup analyses were associated with more positive study outcomes. The mAbs directed against alarmins intervene early in the inflammatory cascade and are the first mAbs found to have efficacy in T2-low asthma. Several randomized controlled trials performed predefined subgroup analyses that included T2-low asthma. Subgroup analyses were associated with positive outcomes and were able to reveal a stronger response in at least 1 subgroup. A better understanding of T2-low subgroups and specific biomarkers is necessary to identify the most responsive target population for a given mAb.
T2-低型哮喘是一种常严重的哮喘亚型，治疗选择有限，缺乏生物治疗药物。先前有报道称，几种针对非 T2 细胞因子的单克隆抗体（mAb）在哮喘中无效。这些试验通常研究了异质的哮喘人群，阴性结果可能与不合适的研究队列有关。基于特定生物标志物更有针对性地选择参与者的方法在治疗严重 T2-高型哮喘方面是有益的。同样，当将以前被认为无效的 mAb 施用于正确的目标人群时，它们可能具有潜在的用途。在这里，我们回顾了 2005 年至 2021 年期间进行的个别临床试验，并评估了所选队列的适宜性、研究终点是否达到以及结果测量是否适合研究各自药物的有效性。我们讨论了 T2-低型哮喘人群中的潜在目标群体，并提出了可能预测治疗反应的生物标志物。此外，我们评估了生物标志物指导方法或亚组分析是否与更积极的研究结果相关。针对警报素的 mAb 可早期干预炎症级联反应，是首批被发现对 T2-低型哮喘有效的 mAb。几项随机对照试验进行了预先指定的亚组分析，其中包括 T2-低型哮喘。亚组分析与阳性结果相关，并能够在至少 1 个亚组中显示出更强的反应。更好地了解 T2-低型哮喘亚组和特定生物标志物对于确定特定 mAb 最敏感的目标人群是必要的。
