Tezepelumab Dramatically Reduces OCS Dependence in Severe Asthma
THE WAYFINDER study, a multicentre, phase 3b, open-label trial, has provided compelling evidence that tezepelumab can substantially reduce oral corticosteroid (OCS) use in patients with severe, uncontrolled asthma.
The study enrolled 382 adults across 68 clinical centres in 11 countries (Argentina, Belgium, Bulgaria, France, Germany, Latvia, Mexico, Poland, Spain, UK, and USA), with 298 participants included in efficacy and safety analyses (69.1% female). All participants were receiving maintenance OCS therapy ranging from 5 to 40 mg per day of prednisone or prednisolone.
High Rates of OCS Reduction and Discontinuation
Following 52 weeks of tezepelumab treatment (210 mg subcutaneously every 4 weeks), 89.9% of patients achieved a maintenance OCS dose of 5 mg per day or less without loss of asthma control. Additionally, 32.2% of participants completely discontinued OCS while maintaining disease stability by Week 28, which increased to 50.3% by Week 52 of tezepelumab treatment. These outcomes were observed across pre-specified subgroups, including patients with varying baseline blood eosinophil counts, fractional exhaled nitric oxide levels, and allergic status, demonstrating the therapy’s broad applicability across diverse severe asthma phenotypes.
Safety Profile and Adverse Events
Tezepelumab was generally well tolerated. Serious adverse events occurred in 9.4% of participants, most commonly asthma exacerbations and pneumonia. Only four patients (1.3%) discontinued treatment due to adverse events. There were two deaths during the study, neither considered related to tezepelumab therapy.
Clinical Implications for OCS-Sparing Strategies
Long-term OCS use is associated with significant risks, including osteoporosis, diabetes, hypertension, and cardiovascular complications. By enabling meaningful OCS reduction or complete discontinuation while preserving asthma control, tezepelumab represents a significant advancement in the management of severe, OCS-dependent asthma.
Reference
Jackson DJ et al. 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; DOI:10.1016/S2213-2600(25)00359-5.
