WAYFINDER: Tezepelumab cuts steroid use in severe asthma

Most patients with severe asthma were able to substantially reduce or entirely discontinue maintenance oral corticosteroid (OCS) use without loss of disease control following treatment with tezepelumab, according to data from the phase 3b WAYFINDER trial.

The data presented by Prof. David Jackson (King's College London, UK) at the ATS 2025 showed that at both 28 and 52 weeks, 88.9% of participants of the WAYFINDER trial (NCT05274815) achieved a maintenance OCS dose of ≤5 mg/day, without loss of asthma control as defined by an increase of ≥0.5 points on the Asthma Control Questionnaire-6 or an exacerbation since the previous visit [1]. Notably, 32.2% had completely discontinued OCS by week 28, rising to 50.3% by week 52.

Tezepelumab, a human monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), was approved as an add-on therapy for severe asthma in 2021. While the earlier phase 3 SOURCE trial suggested a steroid-sparing effect, it did not meet its primary endpoint [2]. These results prompted the larger, more definitive WAYFINDER study, which enrolled 298 adults (mean age 54, 69% women) with severe asthma who had been on high-dose inhaled corticosteroids plus long-acting beta-agonists and chronic daily OCS (mean dose 10.8 mg/day) for at least 3 months. All participants had experienced at least 1 asthma exacerbation in the year prior to enrolment.

Patients received tezepelumab 210 mg subcutaneously every 4 weeks. After a 4-week period of stable OCS dosing, tapering was attempted in 1–5 mg increments every 1 to 4 weeks, depending on the baseline dose. Tapering was conditional on stable asthma control and normal adrenal function. Adrenal sufficiency was monitored using morning cortisol levels and ACTH stimulation tests.

Importantly, steroid tapering was halted following a second asthma worsening or if tests revealed complete adrenal insufficiency. Tapering could resume more cautiously if the participants opted to proceed following adrenal recovery.

At 52 weeks, efficacy was observed across subgroups, including baseline eosinophil count, FeNO levels, allergy status, and initial OCS dose. However, participants on >10 mg/day of OCS at baseline were less likely to reach ≤5 mg/day or achieve full discontinuation.

Secondary endpoints showed meaningful clinical benefits. The annualised asthma exacerbation rate dropped from 1.80 to 0.57, with 66.9% remaining exacerbation-free at 52 weeks. Post-bronchodilator FEV₁ improved significantly (mean increase: 0.07 L; 95% CI 0.02–0.11), despite the OCS taper. Quality-of-life and asthma control scores also improved significantly.

Prof. Jackson pointed out that the absence of a comparator arm limits interpretation. Nevertheless, these findings strongly support the role of tezepelumab in steroid-sparing strategies for severe asthma, potentially reducing long-term steroid-related comorbidities including osteoporosis, cardiovascular disease, metabolic complications, and psychiatric effects.

1. Jackson DJ, et al. Tezepelumab Reduces and Eliminates OCS Use in OCS-Dependent Patients with Severe Asthma: Primary Results From the Phase 3b WAYFINDER Study. Mini Symposium, ATS International Conference, 16–21 May 2025, San Francisco, CA, USA.
2. Wechsler ME, et al. Lancet Respir Med. 2022 Jul;10(7):650-660.

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Posted on 26 May 202526 May 2025