TEZEPELUMAB oral corticosteroid reduction in severe asthma achieved meaningful steroid sparing without loss of asthma control.
Study Design and Patient Population
The WAYFINDER Phase IIIb trial evaluated tezepelumab in adults with severe uncontrolled asthma who required daily maintenance oral corticosteroids despite high dose inhaled therapy and additional controllers. Investigators enrolled 382 adults aged 18 to 80 years across 68 centers in 11 countries, and 298 were included in the efficacy and safety analyses. The mean baseline maintenance oral corticosteroid dose was 10.8 mg of prednisone or prednisolone per day.
Participants received tezepelumab 210 mg administered subcutaneously every four weeks for up to 52 weeks. The co-primary endpoints were the proportions of patients who reduced their maintenance oral corticosteroid dose to 5 mg per day or less without loss of asthma control and those who completely discontinued oral corticosteroids without loss of asthma control. Reductions below 5 mg per day required evidence of preserved adrenal function.
Tezepelumab Oral Corticosteroid Reduction Outcomes at 52 Weeks
By week 28, 88.9% of patients had reduced their maintenance oral corticosteroid dose to 5 mg per day or less without loss of asthma control, and this proportion was 89.9% at week 52. Oral corticosteroid discontinuation without loss of asthma control was achieved in 32.2% of patients at week 28 and 50.3% at week 52. These oral corticosteroid reduction and discontinuation benefits were observed across predefined subgroups based on baseline blood eosinophil counts, fractional exhaled nitric oxide levels, and allergy status.
The study highlights the burden of long-term oral corticosteroid use in severe asthma, including risks of osteoporosis, diabetes, ocular complications, infections, renal impairment, and mental health effects. The ability of tezepelumab to enable substantial oral corticosteroid reduction while maintaining asthma control suggests broad applicability across severe asthma phenotypes that are dependent on systemic steroids.
Safety Profile and Clinical Implications
Serious adverse events occurred in 9.4% of patients, most commonly worsening asthma and pneumonia, and 1.3% discontinued tezepelumab because of adverse events. Two deaths occurred during the study and were not considered related to tezepelumab treatment. Overall, the safety profile was consistent with previous experience.
For clinicians managing adults with corticosteroid dependent severe uncontrolled asthma, these findings indicate that tezepelumab oral corticosteroid reduction can be a realistic goal and that complete withdrawal of oral corticosteroids is achievable for about half of patients over one year while maintaining asthma control.
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. The Lancet Respiratory Medicine. 2025;doi:10.1016/S2213-2600(25)00359-5.
