Biomarkers and Clinical Outcomes after Tezepelumab Cessation: Extended Follow-Up from the 2-Year DESTINATION Study

BackgroundLong-term tezepelumab treatment in the DESTINATION study (NCT03706079) resulted in reduced asthma exacerbations, reduced biomarker levels and improved lung function and symptom control in patients with severe, uncontrolled asthma.ObjectiveTo explore time course of changes in biomarkers and clinical manifestations following treatment cessation after 2 years of tezepelumab treatment.MethodsDESTINATION was a two-year, phase 3, multicenter, randomized, placebo-controlled, double-blind study of tezepelumab treatment in patients (12–80 years old) with severe asthma. Patients received their last treatment doses at week 100 and could enroll in an extended follow-up (EFU) period from week 104 to 140. Change over time in key biomarkers and clinical outcomes were assessed in tezepelumab versus placebo recipients for 40 weeks after stopping treatment.ResultsOf 569 patients enrolled in the EFU period, 426 were included in the analysis (289 received tezepelumab and 137 placebo). Over the 40-week period after the last tezepelumab dose, blood eosinophil counts (BEC), fractional exhaled nitric oxide (FeNO) levels and Asthma Control Questionnaire-6 scores gradually increased from weeks 4–10, with a gradual reduction in pre-bronchodilator forced expiratory volume in 1 second such that BECs, FeNO levels and clinical outcomes returned to placebo levels; however, none of these outcomes returned to baseline levels. Total immunoglobulin E levels increased later from week 28 and remained well below placebo and baseline levels during the 40-week period after the last tezepelumab dose.ConclusionThis analysis demonstrates benefits of continued tezepelumab treatment in the management of patients with severe, uncontrolled asthma, compared with stopping treatment after 2 years.