Michael E Wechsler, Christopher E Brightling, Guy Brusselle, Marco Caminati, Tamara Soler, Efraín Montano Gonzalez, Narongwit Nakwan, Iwona Cąpała-Szczurko, Gillian Hunter, Gun Almqvist, Harbans Lal, Piotr Kabelis, Paola Scrigner, Yuko Matsunaga, N Molfino, Sandhia S Ponnarambil, Adalberto Rubin, Adelmir Machado, Andreia Pez, Cristiano Silva, Luiz Felipe Mendes, S Tanni, Waldo Luis de Mattos, MARTTI ANTILA, George Philteos, Andreanne Cote, Patricia Schonffeldt Guerrero, Maite Oyonarte, Felipe Astorga, Patricio Vallejo, Georgina Miranda, Tamara Soler, Angélica Bello, Victor Martinez, Milan Sova, Ilona Pavlišová, Petr Kopecký, Irena Krčmová, Jaromir Zatloukal, Radka Mokošová, Manoj Yadav, Piyush Arora, Anand Kumar, Dante Hernández Colín, Efraín Montano Gonzalez, Sandra González Díaz, Ricardo Campos Cerda, Carla Sanchez Rios, Amado Ramírez Hernández, Jose Ramón Arribas López, Nancy Velásquez, Sławomir Tokarski, Anna Olech-Cudzik, Danuta Mądra-Rogacka, Joanna Nowacka-Apiyo, Grzegorz Gąsior, Renata Bijata-Bronisz, Justyna Kolodynska-Jeridi, Mateusz Łukaszyk, Piotr Lacwik, Kwang Ha Yoo, You Sook Cho, Hae-Sim Park, Deog Young Kim, Thitiwat Sriprasart, Siwasak Juthong, Narongwit Nakwan, Piamlarp Sangsayunh, Dilsat Mungan, Sevim Bavbek, Özlem Göksel, Dane Ediger, Sait Karakurt, Michael Wechsler, Carlo Hatem, Camil Kreit, Hummayun Ismail, Idalia Acosta, Samuel DeLeon, Ryan Klein, Allen Machado, Jadelis Giquel
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.