Efficacy and safety of tezepelumab versus placebo in reducing oral corticosteroid use in adults with severe, oral corticosteroid-dependent asthma (SUNRISE): a multicentre, placebo-controlled, double-blind, phase 3 trial.

This study aimed to evaluate the oral corticosteroid-sparing effect of tezepelumab in adults with severe, oral corticosteroid-dependent asthma.

本研究旨在评估Tezepelumab在严重依赖口服皮质类固醇的成人哮喘患者中减少口服皮质类固醇使用的效果。

Methods

SUNRISE was a phase 3, double-blind, placebo-controlledtrial conducted across 63 sites in 12 countries.

SUNRISE 是一项在12个国家的63个地点进行的3期、双盲、安慰剂对照试验。

After oral corticosteroid optimisation, participants aged 18-80 years with physician-diagnosed asthma who were receiving medium-dose or high-dose inhaled corticosteroids for at least 12 months before screening were randomly assigned (2:1) to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 28 weeks.

在口服皮质类固醇优化后，年龄在18-80岁之间，由医生诊断为哮喘的参与者，他们在筛选前至少12个月接受了中剂量或高剂量的吸入皮质类固醇治疗，被随机分配（2:1）每4周皮下注射210毫克的tezepelumab或安慰剂，为期28周。

Participants were stratified by region and blood eosinophil count.

受试者按地区和血液嗜酸性粒细胞计数进行分层。

Participants, investigators, and site staff were masked to treatment assignment.

参与者、研究者和现场工作人员对治疗分配情况进行了盲法处理。

The primary outcome was the categorised percentage reduction from baseline in the daily maintenance oral corticosteroid dose at week 28 while maintaining asthma control.

主要结果是28周时，维持哮喘控制的同时，每日维持口服皮质类固醇剂量从基线开始的分类百分比减少。

The primary outcome and safety outcomes were evaluated in all randomly assigned participants who received at least one dose of tezepelumab or placebo (ie, the full analysis set).

主要结果和安全性结果在所有随机分配的参与者中进行了评估，这些参与者至少接受了一次tezepelumab或安慰剂治疗（即全分析集）。

This study is registered with ClinicalTrials.gov (NCT05398263).

本研究已在ClinicalTrials.gov注册（NCT05398263）。

Results

Between Aug 9, 2022, and March 24, 2025, when the study was terminated, 122 of 207 planned participants received tezepelumab (n=83) or placebo (n=39). 90 (74%) participants completed treatment.

在2022年8月9日至2025年3月24日期间，当研究终止时，原计划的207名参与者中有122人接受了tezepelumab（n=83）或安慰剂（n=39）。90名（74%）参与者完成了治疗。

Of 122 participants, 25 (20%) did not complete the study owing to early study termination due to recruitment challenges.

在122名参与者中，由于招募挑战导致研究提前终止，有25人（20%）未能完成研究。

The odds of reaching a category of greater percentage oral corticosteroid reduction at week 28 were significantly higher with tezepelumab than placebo (odds ratio 2·93 [95% CI 1·43-6·03]; p=0·0034).

在第28周时，与安慰剂相比，使用tezepelumab达到更高百分比口服皮质类固醇减少类别的几率显著更高（优势比2.93 [95% 置信区间1.43-6.03]；p=0.0034）。

Overall, 25 (30%) participants in the tezepelumab group and 23 (59%) participants in the placebo group had at least one asthma exacerbation over 28 weeks.

在28周的研究期间，接受tezepelumab治疗的25名（30%）参与者和接受安慰剂治疗的23名（59%）参与者中，至少有一人经历了哮喘加重。

Adverse events occurred in 47 (57%) participants in the tezepelumab group and 28 (72%) participants in the placebo group.

在tezepelumab组中有47名（57%）参与者和在安慰剂组中有28名（72%）参与者出现了不良事件。

Serious adverse events occurred in seven (8%) participants in the tezepelumab group and five (13%) participants in the placebo group.

在使用特泽普鲁单抗的组别中，有7名（8%）参与者出现了严重不良事件，在使用安慰剂的组别中，有5名（13%）参与者出现了严重不良事件。

Three deaths occurred (two in the tezepelumab group during the post-treatment period and one in the placebo group during the treatment period); none were considered causally related to study treatment based on investigator assessment.

发生了三起死亡事件（特泽普鲁单抗组在治疗后期间有两起，安慰剂组在治疗期间有一起）；基于研究者评估，这些死亡均未被认为与研究治疗有因果关系。

interpretation

In this study, tezepelumab treatment led to greater reductions from baseline in daily oral corticosteroid dose than placebo at week 28 despite early study termination.

在这项研究中，尽管研究提前终止，但与安慰剂相比，tezepelumab治疗在第28周时，从基线开始的每日口服皮质类固醇剂量减少更多。

No safety concerns were identified for tezepelumab.

未发现tezepelumab的安全性问题。

These findings show that patients receiving tezepelumab can reduce maintenance oral corticosteroid use while maintaining asthma control and without compromising efficacy.

这些发现表明，接受tezepelumab治疗的患者可以在维持哮喘控制的同时减少维持性口服皮质类固醇的使用，且不会降低疗效。

funding

AstraZeneca and Amgen.

阿斯利康和安进。