特泽鲁单抗治疗激素依赖型重度哮喘：90%减量、超半数停用口服糖皮质激素
2026/03/30
摘要
研究背景：2022年发表的特泽鲁单抗3期临床试验（SOURCE研究）结果表明，对于基线血嗜酸性粒细胞计数（BEC）≥150个/μL的口服糖皮质激素（OCS）依赖型哮喘患者，该药物展现出了明确的OCS减量效应。基于此，本研究旨在更大样本队列中，进一步评估特泽鲁单抗对于激素依赖型的重度未控制哮喘患者减停OCS的疗效。
研究方法：WAYFINDER是一项3b期、多中心、单臂、开放标签的OCS减量研究。研究从11个国家的68个临床中心招募18~80岁的重度未控制哮喘受试者。核心入组标准为：规律接受高剂量ICS联合LABA治疗≥6个月、依赖泼尼松或泼尼松龙（5~40 mg/d或等效剂量）维持治疗≥3个月、且近12个月内至少发生1次哮喘急性发作。试验期间，受试者每4周皮下注射特泽鲁单抗210 mg，治疗最长达52周。共同主要终点为第28周和第52周时，在哮喘控制维持的前提下，OCS维持剂量降至≤5 mg/d以及完全停用OCS的受试者比例。仅当受试者肾上腺皮质功能正常时，才可将OCS减至5 mg/d以下。
研究结果：研究于2022年5月17日至2024年9月9日开展。共招募382例受试者，其中298例（女性206例，69.1%）接受了特泽鲁单抗治疗，并纳入疗效与安全性分析。基线平均OCS维持剂量为10.8 ± 6.5 mg/d。在哮喘控制维持的情况下，OCS维持剂量降至≤5 mg/d的患者比例，在第28周时为88.9%（265/298，95% CI: 84.8~92.3），至第52周时为89.9%（268/298，95% CI: 85.9~93.1）；第28周时停用OCS的患者比例为32.2%（96/298，95% CI: 26.9~37.8），至第52周时为50.3%（150/298，95% CI: 44.5~56.2）。此外，基于基线BEC、呼出气一氧化氮（FeNO）水平及过敏状态划分的各项预设亚组分析，均证实了OCS减停的临床获益。安全性方面，严重不良事件28例（9.4%），最常见为哮喘13例、肺炎3例，4例（1.3%）因不良事件终止治疗。研究期间死亡2例，经评估均与特泽鲁单抗无因果关系。
研究结论：经过52周的特泽鲁单抗治疗，近90%的OCS依赖型重度未控制哮喘患者可将OCS维持剂量降至≤5 mg/d，超过半数完全停用OCS，同时维持哮喘控制。研究结果表明，特泽鲁单抗能降低重度哮喘患者的OCS暴露及相关负担，且在多种患者表型中均具有广泛的适用性。
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.
研究背景：2022年发表的特泽鲁单抗3期临床试验（SOURCE研究）结果表明，对于基线血嗜酸性粒细胞计数（BEC）≥150个/μL的口服糖皮质激素（OCS）依赖型哮喘患者，该药物展现出了明确的OCS减量效应。基于此，本研究旨在更大样本队列中，进一步评估特泽鲁单抗对于激素依赖型的重度未控制哮喘患者减停OCS的疗效。
研究方法：WAYFINDER是一项3b期、多中心、单臂、开放标签的OCS减量研究。研究从11个国家的68个临床中心招募18~80岁的重度未控制哮喘受试者。核心入组标准为：规律接受高剂量ICS联合LABA治疗≥6个月、依赖泼尼松或泼尼松龙（5~40 mg/d或等效剂量）维持治疗≥3个月、且近12个月内至少发生1次哮喘急性发作。试验期间，受试者每4周皮下注射特泽鲁单抗210 mg，治疗最长达52周。共同主要终点为第28周和第52周时，在哮喘控制维持的前提下，OCS维持剂量降至≤5 mg/d以及完全停用OCS的受试者比例。仅当受试者肾上腺皮质功能正常时，才可将OCS减至5 mg/d以下。
研究结果：研究于2022年5月17日至2024年9月9日开展。共招募382例受试者，其中298例（女性206例，69.1%）接受了特泽鲁单抗治疗，并纳入疗效与安全性分析。基线平均OCS维持剂量为10.8 ± 6.5 mg/d。在哮喘控制维持的情况下，OCS维持剂量降至≤5 mg/d的患者比例，在第28周时为88.9%（265/298，95% CI: 84.8~92.3），至第52周时为89.9%（268/298，95% CI: 85.9~93.1）；第28周时停用OCS的患者比例为32.2%（96/298，95% CI: 26.9~37.8），至第52周时为50.3%（150/298，95% CI: 44.5~56.2）。此外，基于基线BEC、呼出气一氧化氮（FeNO）水平及过敏状态划分的各项预设亚组分析，均证实了OCS减停的临床获益。安全性方面，严重不良事件28例（9.4%），最常见为哮喘13例、肺炎3例，4例（1.3%）因不良事件终止治疗。研究期间死亡2例，经评估均与特泽鲁单抗无因果关系。
研究结论：经过52周的特泽鲁单抗治疗，近90%的OCS依赖型重度未控制哮喘患者可将OCS维持剂量降至≤5 mg/d，超过半数完全停用OCS，同时维持哮喘控制。研究结果表明，特泽鲁单抗能降低重度哮喘患者的OCS暴露及相关负担，且在多种患者表型中均具有广泛的适用性。
（南方医科大学南方医院 段璇 陈垚欣 赵海金）
（Jackson D, Lugogo N, Gurnell M et al. Oral corticosteroid reduction and discontinuation in adults with corticosteroid-dependent, severe, uncontrolled asthma treated with tezepelumab (WAYFINDER): a multicentre, single-arm, phase 3b trial. The Lancet Respiratory Medicine, Lancet Respir Med. 2026 Feb;14(2):129-140）
Abstract（Jackson D, Lugogo N, Gurnell M et al. Oral corticosteroid reduction and discontinuation in adults with corticosteroid-dependent, severe, uncontrolled asthma treated with tezepelumab (WAYFINDER): a multicentre, single-arm, phase 3b trial. The Lancet Respiratory Medicine, Lancet Respir Med. 2026 Feb;14(2):129-140）
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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小气道功能障碍影响成人哮喘临床缓解：ATLANTIS研究事后分析
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过敏性鼻炎会放大慢性鼻窦炎患者的哮喘风险：一项大规模回顾性队列分析
