Tezepelumab demonstrates steroid-sparing potential in patients with severe asthma, reducing maintenance oral corticosteroid use while maintaining asthma control, as shown in the phase III SUNRISE study.
SUNRISE was terminated prematurely due to recruitment challenges, reported lead researcher Prof Michael Wechsler from National Jewish Health, Denver, Colorado, US, and colleagues. “Despite the smaller than planned sample size, the study met its primary outcome.”
After 28 weeks of treatment, 69 percent of tezepelumab-treated patients achieved a >50-percent reduction in daily maintenance oral corticosteroid dose without loss of asthma control as opposed to 44 percent of those who received placebo. Furthermore, 35 percent of patients in the tezepelumab arm vs 21 percent in the placebo arm were completely off oral corticosteroids by week 28. [Lancet Respir Med 2026;doi:10.1016/S2213-2600(26)00076-7]
Compared with placebo, tezepelumab was associated with around threefold greater odds of reaching a category of greater percentage oral corticosteroid reduction at week 28 (odds ratio, 2.93, 95 percent confidence interval, 1.43–6.03; p=0.0034). Subgroup analyses defined by blood eosinophil count at baseline yielded consistent results.
The mean final daily oral corticosteroid doses were 6.33 mg in the tezepelumab arm vs 8.27 mg in the placebo arm, with 59 percent vs 38 percent of patients in the respective treatment arms using a daily maintenance dose of not more than 5 mg.
Over 28 weeks, at least one episode of asthma exacerbation occurred in 30 percent of tezepelumab-treated patients and in 59 percent of those who received placebo. The annualized asthma exacerbation rate was 0.64 with tezepelumab vs 2.04 with placebo (rate ratio, 0.31, 95 percent CI, 0.19–0.51; p<0.0010).
“Tezepelumab was well tolerated, and no new safety concerns were identified,” said Wechsler and colleagues.
Adverse events (AEs) occurred in 57 percent of patients in the tezepelumab arm and 72 percent in the placebo arm, with the most common being nasopharyngitis. Serious AEs were reported in 8 percent and 13 percent of patients in the respective treatment arms.
Three deaths were documented, two in the tezepelumab arm during the post-treatment period and one in the placebo group during the treatment period. None of these deaths were considered causally related to study treatment.
Taken together, “these findings suggest that, in clinical practice, tezepelumab could provide a potential oral corticosteroid-sparing treatment option for patients with severe, oral corticosteroid-dependent asthma,” the researchers said.
In a press statement, Wechsler highlighted the importance of the data, given that “long-term oral corticosteroid use can have devastating consequences for patients, including diabetes, osteoporosis, cardiovascular disease, and significant impacts on quality of life.”
SUNRISE study
Conducted across 63 sites in 12 countries, SUNRISE included 122 of the planned 207 adult patients with severe asthma who were receiving medium-dose inhaled corticosteroids (500-μg fluticasone propionate or equivalent) or high-dose inhaled corticosteroids (>500-μg fluticasone propionate or equivalent) for at least 12 months before screening. Additionally, these patients had to have been receiving a long-acting beta-agonist for at least 3 months before screening and have had at least one asthma exacerbation in the 24 months before screening.
The mean age of the patients was 52.2 years, with 75 percent female and 55 percent White. The mean baseline blood eosinophil count was 398.6 cells per μL, and the mean BMI was 30.7 kg/m2. The mean daily oral corticosteroid dose at baseline was 13.8 mg.
Following an oral corticosteroid optimization phase of up to 8 weeks, the patients were randomly assigned to receive treatment with tezepelumab 210 mg (n=83) or placebo (n=39). Treatment was administered subcutaneously every 4 weeks for 28 weeks.
Along with the reductions in daily oral corticosteroid dose, tezepelumab treatment led to reductions in asthma exacerbations and improvements in lung function, asthma symptom control, and health-related quality of life compared with placebo at week 28.