接受特泽鲁单抗治疗的皮质醇依赖、严重、未控制哮喘的成人口服皮质醇减少和停药研究（WAYFINDER）：一项多中心、单臂、
2025/12/30
摘要
背景：特泽鲁单抗的SOURCE 3期口服皮质醇（OCS）减量研究表明，在OCS依赖性哮喘患者和基线血液嗜酸性粒细胞计数（BEC）至少为150个/μL的患者中，特泽鲁单抗与安慰剂相比具有OCS减量效果。
目的：WAYFINDER研究旨在进一步评估特泽鲁单抗在样本量更大的OCS依赖、严重、未控制哮喘患者队列中减少或停用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。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个临床中心招募了患有严重、未控制哮喘的成年人（18-80岁），他们每天接受5—40mg（或同等剂量）的泼尼松或泼尼松龙的OCS维持剂量。参与者每4周皮下注射一次210 mg的特泽鲁单抗，持续52周。在第28周和第52周评估的共同主要终点是将处方的OCS维持剂量减少到每天5mg或更少而哮喘仍可控制的受试者比例，以及在哮喘可控情况下停用OCS的受试者比例。OCS剂量减少到每天5mg以下取决于受试者的肾上腺功能。这项完成的研究已在ClinicalTrials.gov上注册，注册号为NCT05274815。
结果：WAYFINDER在2022年5月17日至2024年9月9日期间进行。总体而言，本研究共纳入382名受试者，其中298名受试者（206名为女性[69.1%]）接受了特泽鲁单抗治疗，并被纳入疗效和安全性分析。OCS的平均基线维持剂量为每天10.8（SD 6.5）mg。在第28周时，每天服用5毫克或更少OCS维持剂量而哮喘仍可控的受试者为265人（88.9%[95%CI 84.8-92.3]），在第52周时为268人（89.9%[85.9-93.1]）。在第28周，298名受试者中有96名（32.2%[26.9-37.8]）在哮喘可控的情况下停用OCS，在第52周，298人中有150名（50.3%[44.5-56.2]）停用OCS。根据基线BEC、呼出气一氧化氮分数或过敏状态，在预先指定的亚组中实现了OCS减量和停药。298名受试者中有28名（9.4%）报告了严重不良事件（哮喘[13名]和肺炎[3名]最常见），4名受试者（1.3%）发生了导致停药的不良事件。两名受试者在研究期间死亡，但两人的死亡均不被认为与特泽鲁单抗治疗有因果关系。
结论：在接受52周的开放标签特泽鲁单抗治疗后，近90%的OCS依赖的、严重的、未控制的哮喘患者的OCS维持剂量为每天5毫克或更低，超过50%的患者在保持哮喘控制的同时完全停用OCS。这些发现表明，特泽鲁单抗治疗可以帮助严重哮喘患者减少OCS的使用及其相关负担，在患者多种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.
Jackson DJ, Lugogo NL, Gurnell M, Heaney LG, Korn S, Brusselle G, Chanez P, Del Olmo R, Llanos JP, Keeling N, Sałapa K, Cook B, Parulekar AD, Kostikas K, Fogel R, Martin N, Chandarana SN.
Abstract
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.
OBJECTIVE: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).
RESULTS: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.
CONCLUSION: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：特泽鲁单抗的SOURCE 3期口服皮质醇（OCS）减量研究表明，在OCS依赖性哮喘患者和基线血液嗜酸性粒细胞计数（BEC）至少为150个/μL的患者中，特泽鲁单抗与安慰剂相比具有OCS减量效果。
目的：WAYFINDER研究旨在进一步评估特泽鲁单抗在样本量更大的OCS依赖、严重、未控制哮喘患者队列中减少或停用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。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个临床中心招募了患有严重、未控制哮喘的成年人（18-80岁），他们每天接受5—40mg（或同等剂量）的泼尼松或泼尼松龙的OCS维持剂量。参与者每4周皮下注射一次210 mg的特泽鲁单抗，持续52周。在第28周和第52周评估的共同主要终点是将处方的OCS维持剂量减少到每天5mg或更少而哮喘仍可控制的受试者比例，以及在哮喘可控情况下停用OCS的受试者比例。OCS剂量减少到每天5mg以下取决于受试者的肾上腺功能。这项完成的研究已在ClinicalTrials.gov上注册，注册号为NCT05274815。
结果：WAYFINDER在2022年5月17日至2024年9月9日期间进行。总体而言，本研究共纳入382名受试者，其中298名受试者（206名为女性[69.1%]）接受了特泽鲁单抗治疗，并被纳入疗效和安全性分析。OCS的平均基线维持剂量为每天10.8（SD 6.5）mg。在第28周时，每天服用5毫克或更少OCS维持剂量而哮喘仍可控的受试者为265人（88.9%[95%CI 84.8-92.3]），在第52周时为268人（89.9%[85.9-93.1]）。在第28周，298名受试者中有96名（32.2%[26.9-37.8]）在哮喘可控的情况下停用OCS，在第52周，298人中有150名（50.3%[44.5-56.2]）停用OCS。根据基线BEC、呼出气一氧化氮分数或过敏状态，在预先指定的亚组中实现了OCS减量和停药。298名受试者中有28名（9.4%）报告了严重不良事件（哮喘[13名]和肺炎[3名]最常见），4名受试者（1.3%）发生了导致停药的不良事件。两名受试者在研究期间死亡，但两人的死亡均不被认为与特泽鲁单抗治疗有因果关系。
结论：在接受52周的开放标签特泽鲁单抗治疗后，近90%的OCS依赖的、严重的、未控制的哮喘患者的OCS维持剂量为每天5毫克或更低，超过50%的患者在保持哮喘控制的同时完全停用OCS。这些发现表明，特泽鲁单抗治疗可以帮助严重哮喘患者减少OCS的使用及其相关负担，在患者多种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 张婧媛 摘译 林江涛 审校）
（Lancet Respir Med. 2025 Nov 26:S2213-2600(25)00359-5. doi: 10.1016/S2213-2600(25)00359-5.）
Oral corticosteroid reduction and discontinuation in adults with corticosteroid-dependent, severe, uncontrolled asthma treated with tezepelumab (WAYFINDER): a multicentre, single-arm, phase 3b trial.
Jackson DJ, Lugogo NL, Gurnell M, Heaney LG, Korn S, Brusselle G, Chanez P, Del Olmo R, Llanos JP, Keeling N, Sałapa K, Cook B, Parulekar AD, Kostikas K, Fogel R, Martin N, Chandarana SN.
Abstract
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.
OBJECTIVE: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).
RESULTS: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.
CONCLUSION: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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