背景:在随机对照试验(RCT)中,生物哮喘疗法可减少急性加重和长期口服糖皮质激素(LTOCS)的使用;然而,不符合随机对照试验条件的患者的结局数据有限.因此,我们调查了真实世界的重度哮喘成人患者对生物制剂的反应性.
方法:在国际重度哮喘登记处(ISAR)中随访≥24周的成年人被分组为那些进行了随访的成年人,或者没有,启动生物制剂(抗IgE,抗IL5/IL5R,抗IL4/13)。在四个方面检查了治疗反应:1秒内用力呼气量(FEV1)增加≥100mL,改善哮喘控制,年度加重率(AER)降低≥50%,和任何LTOCS剂量减少。超反应标准为:FEV1增加≥500mL,新的良好控制的哮喘,没有恶化,和LTOCS停止或逐渐减少至≤5毫克/天。
结果:5.3%的ISAR患者符合基本RCT纳入标准;2116/8451开始使用生物制剂。生物引发剂的基线损害比非引发剂更严重,尽管具有相似的生物标志物水平。一半或更多的引发剂有治疗反应:AER降低59%,FEV1增加54%,控制提高49%,降低49%的LTOCS,其中32%,19%,30%,39%,分别,是超级回应。生物引发剂的反应/超反应比非引发剂的反应/超反应更频繁;尽管如此,约40-50%的引发剂不满足响应标准。
结论:大多数重度哮喘患者不适合接受生物治疗的随机对照试验。尽管具有相似的生物标志物水平,但具有比非起始者更差的基线损伤的患者开始使用生物制剂。尽管生物启动剂在所有结局领域都表现出临床反应和超反应,40-50%不符合反应标准。
BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.
METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day.
RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria.
CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.