Nearly 90% of patients with severe asthma who were treated with subcutaneous tezepelumab during the course of 52 weeks achieved meaningful reductions in the use of oral corticosteroids (OCS) and more than half were able to halt their use altogether.1
In addition, more than 80% of patients were able to reduce their maintenance OCS dose to ≤ 5 mg/day when systemic corticosteroid treatment was related to adrenal insufficiency.1
These key findings from an open-label study were recently published in the American Journal of Respiratory and Critical Care Medicine.
“We are well aware of the many negative side effects related to oral corticosteroids in patients and are learning more about the chronic implications of oral corticosteroids related to risks of developing diabetes, osteoporosis, fractures, and many other conditions,” said Stephen T. Doyle, DO, MBA, FCCP, a pulmonary and critical care physician who practices in Grand Rapids, Michigan. “This study attempts to document a treatment for this patient population that can help reduce oral corticosteroid use and thus limit the negative consequences related to steroids.”
Tezepelumab, a human monoclonal antibody that blocks thymic stromal lymphopoietin, was approved by the US Food and Drug Administration in 2021 as an add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.2 Use of tezepelumab in an earlier phase 3 trial of 150 patients—the Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma (SOURCE) trial—failed to reach its primary end point of significantly reducing OCS dose without loss of asthma control. However, a subgroup analysis showed efficacy of tezepelumab in patients with baseline blood eosinophil counts ≥ 150 cells/μL.3 In the Extension Study to Evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents With Severe, Uncontrolled Asthma (DESTINATION) trial, patients with severe asthma from the SOURCE study and another trial were followed for an additional 52 weeks (for a total of 104 weeks). By week 104, 66.7% of patients receiving tezepelumab had discontinued OCS, compared with 46.9% of those receiving placebo.4
For the current phase 3b study—known as the Study to Evaluate Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma (WAYFINDER) trial—researchers evaluated whether the use of tezepelumab in a cohort of 298 patients with severe asthma who were dependent on OCS would lead to a reduction or discontinuation of OCS use without loss of asthma control over 52 weeks. They administered tezepelumab 210 mg subcutaneously every four weeks. Following a four-week induction phase on a stable OCS dose, patients entered a 48-week phase focused on OCS dose reduction and maintenance.1
The co-primary end points, assessed at weeks 28 and 52, were the proportions of participants who reduced their daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control and those who discontinued OCS entirely without loss of asthma control. Reductions in OCS dose to < 5 mg/day were contingent on participants maintaining adequate adrenal function, assessed initially by a morning serum cortisol test and followed by either adrenocorticotropic hormone stimulation tests or repeat morning cortisol measurements.1
In all, 273 patients completed the study, and their mean baseline maintenance OCS dose was 10.8 (6.5) mg/day. At week 28, 88.9% of participants were on a maintenance OCS dose of ≤ 5 mg/day, with a slight increase to 89.9% observed by week 52. In addition, by week 28, 32.2% of participants had stopped using OCS, with the proportion rising to 50.3% by week 52.1
Finally, at week 52, 82.2% of patients maintained a maintenance OCS dose of ≤ 5 mg/day without loss of asthma control when systemic corticosteroid use was due to adrenal insufficiency. Tezepelumab’s safety profile was consistent with previous studies.1
“This study shows a clinically meaningful reduction in oral corticosteroid dosing by using tezepelumab, which provides more evidence of clinicians using this to get patients off steroids,” Dr. Doyle said.
A breakdown of the primary outcome by different eosinophil levels would have been valuable to include, he added, noting that the study also raises two key questions:
- Are the results sustained over the long term, or would patients eventually need to resume steroid therapy?
- Would the benefits persist if tezepelumab were discontinued, or would patients have to return to corticosteroids?
Additionally, Sandhya Khurana, MD, FCCP, Professor of Pulmonary and Critical Care Medicine at the University of Rochester Medical Center, who was not involved in the WAYFINDER study, noted that the lack of a placebo control group is a major limitation.
“Previous studies have shown that patients are often overdosed with maintenance OCS and can reduce their dose during the optimization phase, even prior to the introduction of a biologic,” Dr. Khurana said. “The results of the WAYFINDER study are important and demonstrate a reduction in exacerbations along with the reduction in maintenance OCS and reassuring safety data. However, a placebo-controlled study is needed to answer this question. Unfortunately, SUNRISE, a phase 3 placebo-controlled randomized controlled trial in OCS-dependent asthma was terminated early due to slow recruitment.”
References
1. Jackson DJ, Lugogo N, Gurnell M, et al. Tezepelumab reduces and eliminates OCS use in OCS-dependent patients with severe asthma: primary results from the phase 3b WAYFINDER study [abstract]. Am J Respir Crit Care Med. 2025;211:A5231. doi:10.1164/ajrccm.2025.211.Abstracts.A5231
2. FDA approves maintenance treatment for severe asthma. US Food and Drug Administration. December 20, 2021.
3. Wechsler ME, Menzies-Gow A, Brightling CE, et al. 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
4. Wechsler ME, Stolz D, Lugogo NL, et al. Oral and inhaled corticosteroid dose reductions with tezepelumab versus placebo in patients with severe, uncontrolled asthma from DESTINATION. J Allergy Clin Immunol Pract. 2024 Nov;12(11):3128-3131.e2. doi:10.1016/j.jaip.2024.08.008
