Tezepelumab is a potential OCS-sparing treatment option for patients with severe, OCS-dependent asthma.In the phase III SUNRISE trial, tezepelumab significantly reduces daily maintenance oral corticosteroid (OCS) dose while maintaining asthma control in adults with severe OCS-dependent asthma, despite early study termination and the smaller-than-planned sample size.
The study met its primary endpoint—the likelihood of reducing OCS dose was nearly threefold higher with tezepelumab vs placebo at week 28 (odds ratio [OR], 2.93; p=0.0034). [Lancet Respir Med 2026;14:481-492]
Week 28 key endpoints
Compared with the placebo group, the tezepelumab group had more participants who achieved reductions from baseline in daily maintenance OCS dose without loss of asthma control (100 percent: 35 percent vs 21 percent; ≥50 percent: 69 percent vs 44 percent) and had a daily maintenance OCS dose of ≤5 mg (59 percent vs 38 percent).
Tezepelumab also outdid placebo in prebronchodilator FEV1* improvements (least-squares mean change from baseline [LSM CFB], 0.24 L vs −0.03 L; pnominal=0.0046), which was observed as early as week 4 and sustained throughout the treatment period.
The cumulative odds of having a category of greater percentage reduction in daily maintenance OCS dose with tezepelumab remained higher irrespective of baseline BEC** (ORs, 1.76, 3.48, 2.66, and 3.30 for <150, ≥150, <300, and ≥300 cells/μL, respectively), as did the prebronchodilator FEV1 improvements (LSM CFB, 0 L vs –0.21 L, 0.30 L vs 0.03 L, 0.13 L vs −0.16 L, and 0.34 L vs 0.07 L, respectively).
Other secondary outcomes, safety
Compared with the placebo group, the tezepelumab group had fewer participants with at least one asthma exacerbation (30 percent vs 59 percent; AAER***, 0.64 vs 2.04; rate ratio [RR], 0.31; pnominal<0.0010) and a lower rate of exacerbations requiring emergency department visit or hospital admission (0.09 vs 0.67; RR, 0.14).
Of note, the first exacerbations occurred earlier with placebo than with tezepelumab (hazard ratio [HR], 0.37; HR <1 favours tezepelumab).
Week 28 also saw greater improvements in ACQ-6# (LSM CFB, −1.23 vs −0.64; p=0.015), AQLQ(S)+12## (LSM CFB, 1.3 vs 0.5; p=0.0064), and SGRQ### scores (LSM CFB, –20.06 vs –8.74; p=0.057) with tezepelumab than with placebo.
The tezepelumab group had fewer adverse events (AEs; 57 percent vs 72 percent) and serious AEs (8 percent vs 13 percent) than the placebo group. The most common AE was nasopharyngitis (13 percent and 18 percent).
The tezepelumab group also had two AEs leading to treatment discontinuation (prostate cancer and plasma cell myeloma) and two deaths during the post-treatment phase, but none of the deaths were deemed treatment related.
Anti-TSLP monoclonal antibody
OCS has been used as an adjunct treatment in severe asthma that is uncontrolled by inhaled corticosteroids and additional controllers. However, OCS use has been associated with AE risk and OCS-related comorbidities and mortality. [Respirology 2019;25:161-172; Allergy 2025;80:2113-2127]
Tezepelumab is an anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody that reduces asthma exacerbation frequency and improves asthma control and lung function in patients with severe, uncontrolled asthma, including those requiring maintenance OCS. [N Engl J Med 2021;384:1800-1809; Lancet Respir Med 2023;11:425-438; Am J Respir Crit Care Med 2023;208:13-24]
TSLP levels are associated with airway obstruction, disease severity, and CS resistance in asthma. [Expert Opin Ther Targets 2020;24:777-792; J Allergy Clin Immunol 2018;141:257-268.e6] Evidence suggests that blocking TSLP downregulates inflammatory pathways, which may improve steroid sensitivity and account for the OCS-sparing effects of tezepelumab. [Allergy 2026;81:277-280]
In the SOURCE study, despite the improvement in participants with baseline BEC ≥150 cells/μL, the study did not meet its primary endpoint of improvement in OCS dose reduction with tezepelumab in the overall cohort. [Lancet Respir Med 2022;10:650-660]
“SUNRISE was designed to account for the limitations of [SOURCE] and to align the study design with previously published OCS-sparing studies of other asthma biologics,” the researchers said. They randomized 122 participants (mean age 52.2 years, 75 percent women, 16 percent Asian) 2:1 to receive SC tezepelumab 210 mg or placebo Q4W for 28 weeks.
Taken together, the SUNRISE findings indicate that tezepelumab-treated patients may reduce maintenance OCS while maintaining asthma control without compromising efficacy outcomes, the researchers said.
“Additionally, tezepelumab treatment led to reductions in exacerbations and improvements in lung function, asthma symptom control, and health-related quality of life vs placebo at week 28, despite the reduction in the daily OCS dose. No new safety concerns were identified for tezepelumab,” they continued.
Hence, tezepelumab is a potential OCS-sparing treatment option for patients with severe, OCS-dependent asthma, they concluded.