特泽鲁单抗对比安慰剂在减少重度口服糖皮质激素依赖性哮喘成人患者口服糖皮质激素使用中的疗效与安全性（SUNRISE研究）：
2026/06/01
摘要
背景：特泽鲁单抗是一种人源化单克隆抗体，可阻断胸腺基质淋巴生成素的活性。本研究旨在评估特泽鲁单抗在重度、口服糖皮质激素依赖性哮喘成人患者中减少口服糖皮质激素使用的效果。
方法：SUNRISE研究是一项在12个国家63个中心开展的3期、双盲、安慰剂对照临床试验。在口服糖皮质激素优化治疗后，将筛选前至少12个月内已接受中剂量或高剂量吸入糖皮质激素治疗的、经医生诊断为哮喘的18-80岁受试者，按2:1的比例随机分配，接受特泽鲁单抗210 mg或安慰剂皮下注射，每4周一次，持续28周。受试者按地区和血嗜酸性粒细胞计数进行分层。受试者、研究者和研究中心工作人员均对治疗分组设盲。主要结局指标为第28周时，在维持哮喘控制的前提下，每日维持性口服糖皮质激素剂量相比基线降低的百分比分级。主要结局和安全性结局在所有至少接受一剂特泽鲁单抗或安慰剂的随机化受试者（即全分析集）中进行评估。本研究已在ClinicalTrials.gov注册（NCT05398263）。
结果：在2022年8月9日至2025年3月24日研究终止期间，在207名计划受试者中，有122名接受了特泽鲁单抗（n=83）或安慰剂（n=39）治疗。共有90名（74%）受试者完成了治疗。在122名受试者中，25名（20%）因入组困难导致研究提前终止而未完成研究。第28周时，特泽鲁单抗组达到更高口服糖皮质激素减量百分比等级的可能性显著高于安慰剂组（优势比 2.93 [95% CI 1.43-6.03]；p=0.0034）。总体而言，在28周内，特泽鲁单抗组有25名（30%）受试者、安慰剂组有23名（59%）受试者出现至少一次哮喘急性发作。不良事件发生情况：特泽鲁单抗组47名（57%），安慰剂组28名（72%）。严重不良事件发生情况：特泽鲁单抗组7名（8%），安慰剂组5名（13%）。共发生3例死亡（特泽鲁单抗组2例发生在治疗结束后，安慰剂组1例发生在治疗期间）；根据研究者评估，均认为与研究治疗无因果关系。
解读：在本研究中，尽管研究提前终止，但第28周时，特泽鲁单抗治疗相比安慰剂能更大程度地降低患者每日口服糖皮质激素的基线水平。未发现特泽鲁单抗存在安全性问题。这些结果表明，接受特泽鲁单抗治疗的患者可以在维持哮喘控制且不牺牲疗效的前提下，减少维持性口服糖皮质激素的使用。
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.
Michael E, Wechsler; Christopher E
Abstrast
BACKGROUND: Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. This study aimed to evaluate the oral corticosteroid-sparing effect of tezepelumab in adults with severe, oral corticosteroid-dependent asthma.
METHODS: SUNRISE was a phase 3, double-blind, placebo-controlled trial conducted across 63 sites in 12 countries. 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. Participants were stratified by region and blood eosinophil count. Participants, investigators, and site staff were masked to treatment assignment. The primary outcome was the categorised percentage reduction from baseline in the daily maintenance oral corticosteroid dose at week 28 while maintaining asthma control. 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). This study is registered with ClinicalTrials.gov (NCT05398263).
FINDINGS: 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. Of 122 participants, 25 (20%) did not complete the study owing to early study termination due to recruitment challenges. 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). 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. Adverse events occurred in 47 (57%) participants in the tezepelumab group and 28 (72%) participants in the placebo group. Serious adverse events occurred in seven (8%) participants in the tezepelumab group and five (13%) participants in the placebo group. 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.
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. No safety concerns were identified for tezepelumab. These findings show that patients receiving tezepelumab can reduce maintenance oral corticosteroid use while maintaining asthma control and without compromising efficacy.
背景：特泽鲁单抗是一种人源化单克隆抗体，可阻断胸腺基质淋巴生成素的活性。本研究旨在评估特泽鲁单抗在重度、口服糖皮质激素依赖性哮喘成人患者中减少口服糖皮质激素使用的效果。
方法：SUNRISE研究是一项在12个国家63个中心开展的3期、双盲、安慰剂对照临床试验。在口服糖皮质激素优化治疗后，将筛选前至少12个月内已接受中剂量或高剂量吸入糖皮质激素治疗的、经医生诊断为哮喘的18-80岁受试者，按2:1的比例随机分配，接受特泽鲁单抗210 mg或安慰剂皮下注射，每4周一次，持续28周。受试者按地区和血嗜酸性粒细胞计数进行分层。受试者、研究者和研究中心工作人员均对治疗分组设盲。主要结局指标为第28周时，在维持哮喘控制的前提下，每日维持性口服糖皮质激素剂量相比基线降低的百分比分级。主要结局和安全性结局在所有至少接受一剂特泽鲁单抗或安慰剂的随机化受试者（即全分析集）中进行评估。本研究已在ClinicalTrials.gov注册（NCT05398263）。
结果：在2022年8月9日至2025年3月24日研究终止期间，在207名计划受试者中，有122名接受了特泽鲁单抗（n=83）或安慰剂（n=39）治疗。共有90名（74%）受试者完成了治疗。在122名受试者中，25名（20%）因入组困难导致研究提前终止而未完成研究。第28周时，特泽鲁单抗组达到更高口服糖皮质激素减量百分比等级的可能性显著高于安慰剂组（优势比 2.93 [95% CI 1.43-6.03]；p=0.0034）。总体而言，在28周内，特泽鲁单抗组有25名（30%）受试者、安慰剂组有23名（59%）受试者出现至少一次哮喘急性发作。不良事件发生情况：特泽鲁单抗组47名（57%），安慰剂组28名（72%）。严重不良事件发生情况：特泽鲁单抗组7名（8%），安慰剂组5名（13%）。共发生3例死亡（特泽鲁单抗组2例发生在治疗结束后，安慰剂组1例发生在治疗期间）；根据研究者评估，均认为与研究治疗无因果关系。
解读：在本研究中，尽管研究提前终止，但第28周时，特泽鲁单抗治疗相比安慰剂能更大程度地降低患者每日口服糖皮质激素的基线水平。未发现特泽鲁单抗存在安全性问题。这些结果表明，接受特泽鲁单抗治疗的患者可以在维持哮喘控制且不牺牲疗效的前提下，减少维持性口服糖皮质激素的使用。
（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 May 18;(0).DOI:10.1016/S2213-2600(26)00076-7. IF: 25.094）
（Lancet Respir Med 2026 May 18;(0).DOI:10.1016/S2213-2600(26)00076-7. IF: 25.094）
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.
Michael E, Wechsler; Christopher E
Abstrast
BACKGROUND: Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. This study aimed to evaluate the oral corticosteroid-sparing effect of tezepelumab in adults with severe, oral corticosteroid-dependent asthma.
METHODS: SUNRISE was a phase 3, double-blind, placebo-controlled trial conducted across 63 sites in 12 countries. 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. Participants were stratified by region and blood eosinophil count. Participants, investigators, and site staff were masked to treatment assignment. The primary outcome was the categorised percentage reduction from baseline in the daily maintenance oral corticosteroid dose at week 28 while maintaining asthma control. 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). This study is registered with ClinicalTrials.gov (NCT05398263).
FINDINGS: 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. Of 122 participants, 25 (20%) did not complete the study owing to early study termination due to recruitment challenges. 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). 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. Adverse events occurred in 47 (57%) participants in the tezepelumab group and 28 (72%) participants in the placebo group. Serious adverse events occurred in seven (8%) participants in the tezepelumab group and five (13%) participants in the placebo group. 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.
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. No safety concerns were identified for tezepelumab. These findings show that patients receiving tezepelumab can reduce maintenance oral corticosteroid use while maintaining asthma control and without compromising efficacy.
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