A new Lancet report describes major progress in reducing dependence on daily oral corticosteroids among people living with severe uncontrolled asthma
The report presents findings of the phase 3b WAYFINDER trial, a large international study designed to evaluate whether long term treatment with tezepelumab can help patients taper or fully discontinue steroid tablets while maintaining control of their disease.
The report builds on earlier evidence from the SOURCE and DESTINATION trials, which suggested that the medicine could support steroid reduction in certain patient groups, but the new study provides a broader and more definitive assessment across a much larger population.
The WAYFINDER study followed adults aged between eighteen and eighty years who had severe asthma that remained uncontrolled despite high dose inhaled therapy and who depended on daily prednisone or prednisolone doses of five to forty milligrams. These participants represented a real world population of patients who often suffer substantial health burdens from long term steroid use.
Chronic exposure to oral corticosteroids is known to increase the risk of osteoporosis diabetes infections ocular problems kidney impairment and mental health effects. Even short term exposure to doses that exceed natural cortisol production can suppress the adrenal system leaving patients at risk of fatigue nausea and life threatening adrenal crises during physical stress.
To address these concerns WAYFINDER was conducted across sixty eight clinical centers in eleven countries including Argentina Belgium Bulgaria France Germany Latvia Mexico Poland Spain the United Kingdom and the United States. Participants received two hundred and ten milligrams of tezepelumab every four weeks for up to fifty two weeks and followed a structured steroid tapering plan that was tailored to their initial dose. Reductions were guided through repeated assessments of adrenal function using morning cortisol testing and when needed stimulation testing. Movement below five milligrams per day required confirmation that adrenal function remained adequate.
Of the three hundred and eighty two individuals enrolled, two hundred and ninety eight received treatment and were included in the main analysis. The average baseline steroid dose was slightly above ten milligrams daily. By week twenty eight nearly eighty nine percent of participants had reduced their maintenance dose to five milligrams or less while retaining asthma control, and by week fifty two this figure approached ninety percent.
The proportion of patients who fully discontinued oral steroids rose from just over thirty two percent at week twenty eight to more than fifty percent at week fifty two. These outcomes were consistent across groups defined by blood eosinophil counts fractional exhaled nitric oxide levels and allergy status, showing that the benefits applied across a wide range of severe asthma profiles.
Safety findings were aligned with the established profile of tezepelumab. Serious adverse events occurred in fewer than ten percent of participants, most commonly asthma exacerbations and pneumonia. A small number discontinued treatment because of adverse events, and two deaths occurred during the study, neither considered related to the treatment.
The Lancet report concludes that after a full year of open label therapy with tezepelumab, almost all patients reduced their steroid use to the physiological minimum required to support normal cortisol levels, and more than half were able to eliminate steroid tablets entirely while maintaining stable asthma control.
The results indicate that the medicine can meaningfully reduce the health burden associated with chronic steroid exposure and provide clinicians with practical guidance on how to safely taper steroids in patients with severe asthma who begin biologic therapy.
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