Tezepelumab 减少重症口服激素依赖型哮喘口服激素用量的 3 期 SUNRISE 试验

原文

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. FUNDING: AstraZeneca and Amgen.