探索重症哮喘患者对生物制剂反应的定义和预测因素
2024/09/29
摘要
背景：生物有效性通常以反应来评估，这个术语没有一致的定义。事实证明，识别那些在现实生活中最有可能做出回应的人是一项挑战。
目的：探讨成人严重哮喘患者生物反应的定义，并调查与生物反应相关的患者特征。
方法：这是一项纵向队列研究，使用了来自21个国家的数据，这些国家与国际严重哮喘登记处共享数据。在开始使用生物制剂之前和之后的1年时间里，对预先确定生物制剂损害程度的患者的四个哮喘结果领域的变化进行了评估。反应终点为急性加重率降低50%或以上，长期口服皮质类固醇日剂量降低50%或以上，哮喘控制的一个或多个类别得到改善，FEV1改善100mL或以上。响应者使用单个和多个域定义。通过多变量分析检验了生物治疗前特征与生物治疗后起始反应之间的关系。
结果:共纳入2210例患者。缓解率从加重缓解的80.7%(701人中有566人)到四域缓解的10.6%(85人中有9人)不等。许多缓解者在生物治疗后仍表现出明显的损害:46.7%(n=206/441)哮喘控制缓解者在生物治疗前哮喘未控制，但在生物治疗后疾病仍未完全控制。反应的预测因子是结果依赖的。反应的预测因素与结果有关。肺功能应答者更有可能具有较高的生物药物使用前FeNO（每增加25个十亿分率的几率=1.20）和较短的哮喘持续时间（每增加 10年的持续时间的几率=0.81）。较高的血嗜酸性粒细胞计数和2型相关合并症的存在与满足长期口服皮质类固醇、对照和肺功能应答标准的较高几率呈正相关。
结论:我们的研究结果强调了反应的多模态性质，表明许多反应者在生物药物启动后经历残留症状，并且反应的预测因子根据评估的结果而变化。
Exploring Definitions and Predictors of Response to Biologics for Severe Asthma
Ghislaine Scelo , Trung N Tran, Tham T Le, et al.
Abstract
BACKGROUND: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.
OBJECTIVE:To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response.
METHODS: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 FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis.
RESULTS: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.
CONCLUSION: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.
背景：生物有效性通常以反应来评估，这个术语没有一致的定义。事实证明，识别那些在现实生活中最有可能做出回应的人是一项挑战。
目的：探讨成人严重哮喘患者生物反应的定义，并调查与生物反应相关的患者特征。
方法：这是一项纵向队列研究，使用了来自21个国家的数据，这些国家与国际严重哮喘登记处共享数据。在开始使用生物制剂之前和之后的1年时间里，对预先确定生物制剂损害程度的患者的四个哮喘结果领域的变化进行了评估。反应终点为急性加重率降低50%或以上，长期口服皮质类固醇日剂量降低50%或以上，哮喘控制的一个或多个类别得到改善，FEV1改善100mL或以上。响应者使用单个和多个域定义。通过多变量分析检验了生物治疗前特征与生物治疗后起始反应之间的关系。
结果:共纳入2210例患者。缓解率从加重缓解的80.7%(701人中有566人)到四域缓解的10.6%(85人中有9人)不等。许多缓解者在生物治疗后仍表现出明显的损害:46.7%(n=206/441)哮喘控制缓解者在生物治疗前哮喘未控制，但在生物治疗后疾病仍未完全控制。反应的预测因子是结果依赖的。反应的预测因素与结果有关。肺功能应答者更有可能具有较高的生物药物使用前FeNO（每增加25个十亿分率的几率=1.20）和较短的哮喘持续时间（每增加 10年的持续时间的几率=0.81）。较高的血嗜酸性粒细胞计数和2型相关合并症的存在与满足长期口服皮质类固醇、对照和肺功能应答标准的较高几率呈正相关。
结论:我们的研究结果强调了反应的多模态性质，表明许多反应者在生物药物启动后经历残留症状，并且反应的预测因子根据评估的结果而变化。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（J Allergy Clin Immunol Pract. 2024 Sep;12(9):2347-2361 DOI: 10.1016/j.jaip.2024.05.016）
（J Allergy Clin Immunol Pract. 2024 Sep;12(9):2347-2361 DOI: 10.1016/j.jaip.2024.05.016）
Exploring Definitions and Predictors of Response to Biologics for Severe Asthma
Ghislaine Scelo , Trung N Tran, Tham T Le, et al.
Abstract
BACKGROUND: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.
OBJECTIVE:To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response.
METHODS: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 FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis.
RESULTS: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.
CONCLUSION: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.
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Benralizumab治疗过敏性哮喘：随机、双盲、安慰剂对照试验
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在特异性吸入激发试验期间持续吸入皮质类固醇治疗对诊断职业性哮喘的影响
