Tezepelumab Cuts Steroid Dependence in Severe Asthma: WAYFINDER trial
UK: A new study published in The Lancet Respiratory Medicine reports that tezepelumab can significantly reduce the need for oral corticosteroids (OCS) in adults with severe, uncontrolled asthma who depend on these medications for daily symptom control.
The findings highlight the therapy’s potential as an effective steroid-sparing option for patients who often face substantial side effects from long-term corticosteroid use.
The phase 3b WAYFINDER trial, led by Prof David J Jackson from Guy’s Severe Asthma Centre, King’s College London, aimed to build on earlier evidence from the SOURCE study, which suggested that tezepelumab may help reduce OCS use in patients with higher baseline blood eosinophil counts. WAYFINDER expanded this investigation to a larger and more diverse group of adults aged 18 to 80 years with severe, uncontrolled asthma requiring maintenance OCS doses ranging from 5 mg to 40 mg of prednisone or prednisolone per day.
Conducted across 68 centres in 11 countries, the trial followed a single-arm, open-label design. Participants received 210 mg of tezepelumab subcutaneously every four weeks for up to 52 weeks. The main goals were to determine how many participants could taper their OCS dose to 5 mg or less—or completely stop OCS—while maintaining asthma control. Reductions below 5 mg were allowed only if adrenal function remained intact, assessed through structured cortisol-based testing.
The findings of the trial were as follows:
- A total of 382 individuals were enrolled, with 298 receiving tezepelumab and included in the final analysis.
- The mean baseline oral corticosteroid dose was 10.8 mg per day.
- By week 52, nearly 90% of participants reduced their OCS dose to 5 mg or less without losing asthma control.
- More than half of the participants (50.3%) fully discontinued OCS by the end of the study.
- Similar improvements were observed as early as week 28, showing a steady tapering trend.
- OCS reduction and discontinuation occurred across all evaluated subgroups, irrespective of eosinophil count, FeNO levels, or allergy status.
- Tezepelumab displayed a favourable safety profile throughout the study.
- Serious adverse events were reported in 9.4% of participants, most commonly asthma-related or cases of pneumonia.
- Only four participants discontinued treatment due to adverse events.
- Two deaths occurred during the study, but neither was considered related to tezepelumab.
The study offers key insights into how a biologic therapy targeting thymic stromal lymphopoietin (TSLP)—an epithelial cytokine involved in asthma pathogenesis—can support meaningful reductions in steroid dependence. The trial’s personalised OCS-tapering protocol, which incorporated proactive adrenal insufficiency monitoring, serves as a practical framework for clinicians seeking to safely reduce steroid exposure in eligible patients.
Results from WAYFINDER reinforce earlier findings from the SOURCE and DESTINATION trials, collectively positioning tezepelumab as a strong candidate for OCS-sparing therapy in severe asthma. With most participants maintaining stable lung function, experiencing improved asthma control, and reporting better quality of life, the study underscores the drug’s broad applicability across asthma phenotypes.
"Overall, the findings show that tezepelumab, when paired with a structured tapering approach, can help patients meaningfully reduce or even eliminate chronic OCS use—alleviating the burden of steroid-related complications and improving long-term management of severe, uncontrolled asthma," the authors concluded.
Reference:
Jackson DJ, Lugogo NL, Gurnell M, Heaney LG, Korn S, Brusselle G, Chanez P, Del Olmo R, Llanos JP, Keeling N, Sałapa K, Cook B, Parulekar AD, Kostikas K, Fogel R, Martin N, Chandarana SN. Oral corticosteroid reduction and discontinuation in adults with corticosteroid-dependent, severe, uncontrolled asthma treated with tezepelumab (WAYFINDER): a multicentre, single-arm, phase 3b trial. Lancet Respir Med. 2025 Nov 26:S2213-2600(25)00359-5. doi: 10.1016/S2213-2600(25)00359-5. Epub ahead of print. PMID: 41317738.
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