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 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.

WAYFINDER研究旨在进一步评估tezepelumab在更大队列的OCS依赖性严重、未控制哮喘患者中减少或停止使用OCS的能力。

Methods

WAYFINDER was a phase 3b, multicentre, single-arm, open-label, OCS-sparing study.

WAYFINDER 是一项 3b 期、多中心、单臂、开放标签、节省口服皮质类固醇（OCS）的研究。

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).

招募了来自 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 个临床中心的成人（18-80 岁）患者，这些患者患有严重、未控制的哮喘，正在接受每天 5-40 mg（或等效剂量）的泼尼松或泼尼松龙的维持性口服皮质类固醇（OCS）治疗。

Participants received tezepelumab 210 mg subcutaneously once every 4 weeks for up to 52 weeks.

参与者每4周皮下注射210 mg的tezepelumab，最多52周。

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.

主要共研究终点是在第28周和第52周评估的，包括减少到每天5 mg或更少的维持性口服皮质类固醇剂量而不失去哮喘控制的参与者比例，以及在不失去哮喘控制的情况下停用口服皮质类固醇的参与者比例。

OCS dose reductions to below 5 mg per day were contingent on participants demonstrating preserved adrenal function.

OCS剂量降至每天5毫克以下取决于参与者展示出的肾上腺功能保持完好。

This completed study was registered with ClinicalTrials.gov (NCT05274815).

这项已完成的研究已在ClinicalTrials.gov上注册（NCT05274815）。

Results

WAYFINDER was conducted between May 17, 2022, and Sept 9, 2024.

WAYFINDER研究于2022年5月17日至2024年9月9日进行。

Overall, 382 participants were enrolled and 298 participants (206 female [69·1%]) received tezepelumab and were included in the efficacy and safety analyses.

总体而言，共有382名参与者被纳入研究，其中298名参与者（女性206名，占69.1%）接受了tezepelumab治疗，并被纳入疗效和安全性分析。

The mean baseline maintenance OCS dose was 10·8 (SD 6·5) mg per day.

基线时维持性口服皮质类固醇（OCS）的平均剂量为每天10.8（标准差6.5）毫克。

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.

在第28周，有265名（88.9% [95% 置信区间 84.8-92.3]）参与者在维持每天不超过5毫克的OCS剂量下，没有失去哮喘控制；在第52周，这一比例为268名（89.9% [95% 置信区间 85.9-93.1]）参与者。

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.

在第28周，298名参与者中有96人（32.2% [26.9-37.8]）在不失去哮喘控制的情况下停用口服皮质类固醇（OCS），而在第52周，298名参与者中有150人（50.3% [44.5-56.2]）实现了这一目标。

OCS reduction and discontinuation were achieved across pre-specified subgroups based on baseline BEC, fractional exhaled nitric oxide level, or allergy status.

基于基线嗜酸性粒细胞计数（BEC）、呼出气一氧化氮分数水平或过敏状态的预先设定的亚组中，实现了OCS的减少和停用。

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.

在298名参与者中，有28人（9.4%）报告了严重不良事件（哮喘[13人]和肺炎[3人]是最常见的），并且有四名参与者（1.3%）因不良事件导致停用tezepelumab。

Two participants died during the study but neither death was considered to be causally related to tezepelumab treatment.

研究期间有两名参与者死亡，但均未被认为是与tezepelumab治疗有因果关系。

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.

在接受52周开放标签的tezepelumab治疗后，近90%的依赖OCS的严重、未控制哮喘患者维持每日OCS剂量为5毫克或更少，超过50%的患者完全停用OCS，同时保持哮喘控制。

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.

这些发现表明，tezepelumab治疗可以帮助严重哮喘患者减少OCS的使用及其相关负担，适用于各种患者表型。

funding

AstraZeneca and Amgen.

阿斯利康和安进。