SUNRISE Trial: Tezepelumab Reduces Steroid Use in Severe Asthma

Patients with severe, oral corticosteroid-dependent asthma achieved a reduction in oral corticosteroid when treated with tezepelumab, according to a recent study published in The Lancet Respiratory Medicine.¹

The phase 3, double-blind, placebo-controlled clinical trial SUNRISE (NCT05398263) assessed the safety and efficacy of tezepelumab in this specific patient population. Previous clinical trials, including the SOURCE and WAYFINDER studies, also assessed tezepelumab in this patient population. While SOURCE did not meet its primary end point,² which researchers attributed largely to study design features, findings from both trials helped shape the SUNRISE protocol.¹ Short- and long-term use of corticosteroids has been associated with a substantial risk of adverse events related to, but not limited to, cardiovascular, metabolic, gastrointestinal, and skeletal effects. However, both clinical trials helped to inform study design and formulate therapy delivery to optimize patient outcomes and thus the study results.¹

Reducing Oral Corticosteroid Dependence Remains a Major Goal in Severe Asthma Care

The SUNRISE clinical trial met its primary end point: categorized percentage reduction in daily maintenance oral corticosteroids from baseline to 28 weeks while maintaining asthma control. There were 122 patients out of 207 included in the final analysis. The study, conducted between August 9, 2022, and March 24, 2025, randomized participants 2:1 to receive 210 mg of tezepelumab or a placebo administered subcutaneously every 4 weeks for 28 weeks.

Only 90 (74%) of patients completed the treatment. Of the 122 patients, 25 (20%) did not complete the study due to recruitment challenges. “Clinical practice has shifted to a reduction in long-term maintenance oral corticosteroid use in severe asthma, which presented difficulties in finding patients who met the study inclusion criteria,” the researchers explained.

The odds of reaching a greater percentage in oral corticosteroid reduction at 28 weeks were significantly higher in the tezepelumab group when compared with the placebo (odds ratio [OR] 2.93 [95% CI 1·43–6·03]; P=.0034).

Secondary outcomes included the proportion of participants who achieved at least a 50% or 100% reduction in oral corticosteroids from baseline and those on a daily maintenance of 5 mg tezepelumab or less at week 28. Additionally, annualized asthma exacerbation rate (AAER) over 28 weeks, rate of exacerbations associated with emergency department visits, and time to first asthma exacerbation were also assessed.

SUNRISE Builds on Earlier Tezepelumab Studies in Difficult-to-Treat Asthma

In the tezepelumab group, 25 (30%) patients had at least one asthma exacerbation over the 28 weeks, compared with 23 (59%) patients in the placebo group. The AAER was also markedly lower with tezepelumab at 0.64 (95% CI, 0.44-0.93) versus 2.04 (95% CI, 1.47-2.83) in the placebo group, a rate ratio of 0.31 (95% CI, 0.19-0.51; P < .001), representing a 69% reduction. The rate of exacerbations requiring an emergency department visit or hospitalization was similarly lower in the tezepelumab group at 0.09 versus 0.67 in the placebo group.

Adverse events occurred in 47 (57%) patients in the tezepelumab group and 28 (72%) patients in the placebo group. The most common adverse event was nasopharyngitis, which affected 11 (13%) patients in the Tezepelumab group and 7 (18%) patients in the placebo group.

Two adverse events, prostate cancer and plasma cell myeloma, led to treatment discontinuation, both in the tezepelumab group. Serious adverse events occurred in 7 (8%) participants in the tezepelumab group and 5 (13%) participants in the placebo group.

The findings may be particularly relevant for clinicians seeking alternatives to long-term corticosteroid therapy in patients with severe asthma who remain difficult to manage despite existing treatments. Given the cumulative toxicity associated with chronic steroid exposure, therapies capable of maintaining asthma control while reducing steroid burden remain an important area of clinical investigation and unmet need.

The study was limited by early termination, resulting in a smaller participant population than planned. And although the patient population was diverse in regard to patient blood eosinophil count, differences in population characteristics limit the validity of such comparisons.

“Despite the smaller-than-planned sample size, the results of the SUNRISE trial show the potential of tezepelumab to reduce maintenance oral corticosteroid use while maintaining asthma control and without compromising the efficacy outcomes,” the study authors concluded.

References

1. Wechsler M, Brightling C, Brusselle G, et al. 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. Lancet Respir Med. 2026;14(6):481-492. doi:10.1016/S2213-2600(26)00076-7

2. Wechsler ME, Menzies-Gow A, Brightling CE, et al, and the SOURCE study group. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study. Lancet Respir Med. 2022;10(7):650-660. doi:10.1016/S2213-2600(21)00537-3