Tezepelumab 治疗依赖性口服皮质类固醇的成人重症、未控制哮喘患者的口服皮质类固醇减量与停用（WAYFINDER
2026/03/05
摘要
背景：关于Tezepelumab的SOURCE 3期口服皮质类固醇（OCS）减量研究显示，在基线血嗜酸性粒细胞计数（BEC）至少为150 cells/μL的OCS依赖性哮喘患者中，与安慰剂相比，Tezepelumab具有OCS减量效应。WAYFINDER研究旨在进一步评估Tezepelumab在更大队列的OCS依赖性重症未控制哮喘患者中，减少或停用OCS的能力。
方法：WAYFINDER是一项3b期、多中心、单臂、开放标签、OCS减量研究。研究从11个国家（阿根廷、比利时、保加利亚、法国、德国、拉脱维亚、墨西哥、波兰、西班牙、英国和美国）的68个临床中心招募了接受维持性OCS剂量为每日5-40 mg泼尼松或泼尼松龙（或等效剂量）的成人（18-80岁）重症未控制哮喘患者。受试者接受Tezepelumab 210 mg皮下注射，每4周一次，持续长达52周。共同主要终点是在第28周和第52周时评估，达到在未失去哮喘控制的情况下将规定的维持性OCS剂量减少至每日5 mg或以下的患者比例，以及在未失去哮喘控制的情况下完全停用OCS的患者比例。将OCS剂量减至每日5 mg以下需要证明受试者的肾上腺功能得以保留。本已完成的研究已在ClinicalTrials.gov注册（NCT05274815）。
结果：WAYFINDER研究于2022年5月17日至2024年9月9日期间进行。总体而言，共纳入382名受试者，其中298名受试者（206名女性 [69.1%]）接受了Tezepelumab治疗并被纳入有效性和安全性分析。基线期维持性OCS平均剂量为每日10.8 mg（标准差 6.5）。在第28周，有265/298名（88.9% [95% CI 84.8-92.3]）受试者在未失去哮喘控制的情况下达到了维持性OCS剂量≤每日5 mg；在第52周，这一比例为268/298名（89.9% [85.9-93.1]）。在第28周，有96/298名（32.2% [26.9-37.8]）受试者在未失去哮喘控制的情况下完全停用OCS；在第52周，这一比例为150/298名（50.3% [44.5-56.2]）。根据基线BEC、呼出气一氧化氮分数或过敏状态预设的亚组分析均显示实现了OCS减量和停用。共有28/298名（9.4%）受试者报告了严重不良事件（最常见为哮喘恶化[13例]和肺炎[3例]），4名受试者（1.3%）因不良事件而停用Tezepelumab。研究期间有两名受试者死亡，但均认为与Tezepelumab治疗无因果关系。
结论：经过52周的开放标签Tezepelumab治疗后，近90%的OCS依赖性重症未控制哮喘患者的维持性OCS剂量降至每日5 mg或以下，超过50%的患者完全停用OCS，同时维持了哮喘控制。这些发现表明，Tezepelumab治疗能够帮助重症哮喘患者减少OCS的使用及其相关负担，且在不同患者表型中具有广泛的适用性。
Oral corticosteroid reduction and discontinuation in adults with corticosteroid-dependent, severe, uncontrolled asthma treated with tezepelumab (WAYFINDER): a multicentre, single-arm, phase 3b trial.
David J, Jackson; Njira L,
Abstrast
BACKGROUND: The SOURCE phase 3 oral corticosteroid (OCS)-sparing study of tezepelumab indicated an OCS-sparing effect with tezepelumab versus placebo in patients with OCS-dependent asthma and baseline blood eosinophil counts (BECs) of at least 150 cells per μL. The WAYFINDER study aimed to further evaluate the ability of tezepelumab to reduce or discontinue OCS use in a larger cohort of patients with OCS-dependent severe, uncontrolled asthma.
METHODS: WAYFINDER was a phase 3b, multicentre, single-arm, open-label, OCS-sparing study. Adults (aged 18-80 years) with severe, uncontrolled asthma receiving a maintenance OCS dose of 5-40 mg per day (or equivalent) of prednisone or prednisolone were recruited from 68 clinical centres across 11 countries (Argentina, Belgium, Bulgaria, France, Germany, Latvia, Mexico, Poland, Spain, UK, and USA). Participants received tezepelumab 210 mg subcutaneously once every 4 weeks for up to 52 weeks. The co-primary endpoints, assessed at weeks 28 and 52, were the proportion of participants who reduced their prescribed maintenance OCS dose to 5 mg per day or less without loss of asthma control and the proportion of participants who discontinued OCS without loss of asthma control. OCS dose reductions to below 5 mg per day were contingent on participants demonstrating preserved adrenal function. This completed study was registered with ClinicalTrials.gov (NCT05274815).
FINDINGS: WAYFINDER was conducted between May 17, 2022, and Sept 9, 2024. Overall, 382 participants were enrolled and 298 participants (206 female [69·1%]) received tezepelumab and were included in the efficacy and safety analyses. The mean baseline maintenance OCS dose was 10·8 (SD 6·5) mg per day. The proportion of participants who had a maintenance OCS dose of 5 mg per day or less without loss of asthma control was 265 of 298 (88·9% [95% CI 84·8-92·3]) at week 28 and 268 of 298 (89·9% [85·9-93·1]) at week 52. The proportion of participants who discontinued OCS without loss of asthma control was 96 of 298 (32·2% [26·9-37·8]) at week 28 and 150 of 298 (50·3% [44·5-56·2]) at week 52. OCS reduction and discontinuation were achieved across pre-specified subgroups based on baseline BEC, fractional exhaled nitric oxide level, or allergy status. Serious adverse events were reported in 28 (9·4%) of 298 participants (asthma [13 participants] and pneumonia [three participants] were the most common), and four participants (1·3%) had adverse events leading to tezepelumab discontinuation. Two participants died during the study but neither death was considered to be causally related to tezepelumab treatment.
INTERPRETATION: After 52 weeks of open-label tezepelumab treatment, nearly 90% of patients with OCS-dependent severe, uncontrolled asthma had a maintenance OCS dose of 5 mg per day or less and more than 50% completely discontinued OCS, while maintaining asthma control. These findings indicate that tezepelumab treatment can help enable patients with severe asthma to reduce their OCS use and its associated burden, with broad applicability across patient phenotypes.
背景：关于Tezepelumab的SOURCE 3期口服皮质类固醇（OCS）减量研究显示，在基线血嗜酸性粒细胞计数（BEC）至少为150 cells/μL的OCS依赖性哮喘患者中，与安慰剂相比，Tezepelumab具有OCS减量效应。WAYFINDER研究旨在进一步评估Tezepelumab在更大队列的OCS依赖性重症未控制哮喘患者中，减少或停用OCS的能力。
方法：WAYFINDER是一项3b期、多中心、单臂、开放标签、OCS减量研究。研究从11个国家（阿根廷、比利时、保加利亚、法国、德国、拉脱维亚、墨西哥、波兰、西班牙、英国和美国）的68个临床中心招募了接受维持性OCS剂量为每日5-40 mg泼尼松或泼尼松龙（或等效剂量）的成人（18-80岁）重症未控制哮喘患者。受试者接受Tezepelumab 210 mg皮下注射，每4周一次，持续长达52周。共同主要终点是在第28周和第52周时评估，达到在未失去哮喘控制的情况下将规定的维持性OCS剂量减少至每日5 mg或以下的患者比例，以及在未失去哮喘控制的情况下完全停用OCS的患者比例。将OCS剂量减至每日5 mg以下需要证明受试者的肾上腺功能得以保留。本已完成的研究已在ClinicalTrials.gov注册（NCT05274815）。
结果：WAYFINDER研究于2022年5月17日至2024年9月9日期间进行。总体而言，共纳入382名受试者，其中298名受试者（206名女性 [69.1%]）接受了Tezepelumab治疗并被纳入有效性和安全性分析。基线期维持性OCS平均剂量为每日10.8 mg（标准差 6.5）。在第28周，有265/298名（88.9% [95% CI 84.8-92.3]）受试者在未失去哮喘控制的情况下达到了维持性OCS剂量≤每日5 mg；在第52周，这一比例为268/298名（89.9% [85.9-93.1]）。在第28周，有96/298名（32.2% [26.9-37.8]）受试者在未失去哮喘控制的情况下完全停用OCS；在第52周，这一比例为150/298名（50.3% [44.5-56.2]）。根据基线BEC、呼出气一氧化氮分数或过敏状态预设的亚组分析均显示实现了OCS减量和停用。共有28/298名（9.4%）受试者报告了严重不良事件（最常见为哮喘恶化[13例]和肺炎[3例]），4名受试者（1.3%）因不良事件而停用Tezepelumab。研究期间有两名受试者死亡，但均认为与Tezepelumab治疗无因果关系。
结论：经过52周的开放标签Tezepelumab治疗后，近90%的OCS依赖性重症未控制哮喘患者的维持性OCS剂量降至每日5 mg或以下，超过50%的患者完全停用OCS，同时维持了哮喘控制。这些发现表明，Tezepelumab治疗能够帮助重症哮喘患者减少OCS的使用及其相关负担，且在不同患者表型中具有广泛的适用性。
（中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校）
（Lancet Respir Med 2026 Feb;14(2):129-140. DOI:10.1016/S2213-2600(25)00359-5. IF: 25.094）
（Lancet Respir Med 2026 Feb;14(2):129-140. DOI:10.1016/S2213-2600(25)00359-5. IF: 25.094）
Oral corticosteroid reduction and discontinuation in adults with corticosteroid-dependent, severe, uncontrolled asthma treated with tezepelumab (WAYFINDER): a multicentre, single-arm, phase 3b trial.
David J, Jackson; Njira L,
Abstrast
BACKGROUND: The SOURCE phase 3 oral corticosteroid (OCS)-sparing study of tezepelumab indicated an OCS-sparing effect with tezepelumab versus placebo in patients with OCS-dependent asthma and baseline blood eosinophil counts (BECs) of at least 150 cells per μL. The WAYFINDER study aimed to further evaluate the ability of tezepelumab to reduce or discontinue OCS use in a larger cohort of patients with OCS-dependent severe, uncontrolled asthma.
METHODS: WAYFINDER was a phase 3b, multicentre, single-arm, open-label, OCS-sparing study. Adults (aged 18-80 years) with severe, uncontrolled asthma receiving a maintenance OCS dose of 5-40 mg per day (or equivalent) of prednisone or prednisolone were recruited from 68 clinical centres across 11 countries (Argentina, Belgium, Bulgaria, France, Germany, Latvia, Mexico, Poland, Spain, UK, and USA). Participants received tezepelumab 210 mg subcutaneously once every 4 weeks for up to 52 weeks. The co-primary endpoints, assessed at weeks 28 and 52, were the proportion of participants who reduced their prescribed maintenance OCS dose to 5 mg per day or less without loss of asthma control and the proportion of participants who discontinued OCS without loss of asthma control. OCS dose reductions to below 5 mg per day were contingent on participants demonstrating preserved adrenal function. This completed study was registered with ClinicalTrials.gov (NCT05274815).
FINDINGS: WAYFINDER was conducted between May 17, 2022, and Sept 9, 2024. Overall, 382 participants were enrolled and 298 participants (206 female [69·1%]) received tezepelumab and were included in the efficacy and safety analyses. The mean baseline maintenance OCS dose was 10·8 (SD 6·5) mg per day. The proportion of participants who had a maintenance OCS dose of 5 mg per day or less without loss of asthma control was 265 of 298 (88·9% [95% CI 84·8-92·3]) at week 28 and 268 of 298 (89·9% [85·9-93·1]) at week 52. The proportion of participants who discontinued OCS without loss of asthma control was 96 of 298 (32·2% [26·9-37·8]) at week 28 and 150 of 298 (50·3% [44·5-56·2]) at week 52. OCS reduction and discontinuation were achieved across pre-specified subgroups based on baseline BEC, fractional exhaled nitric oxide level, or allergy status. Serious adverse events were reported in 28 (9·4%) of 298 participants (asthma [13 participants] and pneumonia [three participants] were the most common), and four participants (1·3%) had adverse events leading to tezepelumab discontinuation. Two participants died during the study but neither death was considered to be causally related to tezepelumab treatment.
INTERPRETATION: After 52 weeks of open-label tezepelumab treatment, nearly 90% of patients with OCS-dependent severe, uncontrolled asthma had a maintenance OCS dose of 5 mg per day or less and more than 50% completely discontinued OCS, while maintaining asthma control. These findings indicate that tezepelumab treatment can help enable patients with severe asthma to reduce their OCS use and its associated burden, with broad applicability across patient phenotypes.
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成人哮喘患者的小气道功能障碍与缓解：哮喘小气道受累评估（ATLANTIS）研究的纵向探索性分析
