Observational and Pragmatic Research Institute, Singapore; Optimum Patient Care Global, Cambridge, United Kingdom.
BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Md.
J Allergy Clin Immunol Pract. 2024 Sep;12(9):2347-2361. doi: 10.1016/j.jaip.2024.05.016. Epub 2024 May 19.
Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging.
To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response.
This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis.
A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria.
Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.
生物疗效通常评估为反应，而这个术语的定义并不一致。在现实生活中确定哪些患者最有可能产生反应已被证明具有挑战性。
探讨成人严重哮喘中生物应答者的定义，并研究与生物应答相关的患者特征。
这是一项使用来自 21 个国家的数据进行的纵向队列研究，这些国家与国际严重哮喘登记处共享数据。在生物制剂治疗前，评估了具有预先设定的生物制剂治疗前损伤水平的患者在 1 年内四个哮喘结局领域的变化。应答者的截止值为：发作率降低 50%或以上、长期口服皮质类固醇日剂量降低 50%或以上、一个或多个哮喘控制类别改善以及 FEV 改善 100 mL 或以上。使用单一和多个领域定义应答者。通过多变量分析检查了生物制剂治疗前特征与生物制剂治疗后反应之间的关系。
共纳入 2210 例患者。应答率范围为：发作应答率为 80.7%（n=701 例中的 566 例），四领域应答率为 10.6%（n=85 例中的 9 例）。许多应答者在接受生物制剂治疗后仍存在显著的损伤：在接受生物制剂治疗前哮喘控制不良的 206 例（n=441 例中的 206 例）哮喘控制应答者中，仍有不完全控制的疾病。反应的预测因素取决于结局。肺功能应答者更有可能有较高的生物制剂前 FeNO（每增加 25 个部分每十亿增加的比值比为 1.20），以及较短的哮喘持续时间（每增加 10 年持续时间的比值比为 0.81）。更高的血嗜酸性粒细胞计数和存在 2 型相关合并症与更高的满足长期口服皮质类固醇、控制和肺功能应答标准的几率呈正相关。
我们的研究结果强调了反应的多模态性质，表明许多应答者在接受生物制剂治疗后仍有残留症状，而且反应的预测因素根据评估的结局而有所不同。
