Biomarkers and clinical outcomes after tezepelumab cessation: extended follow-up from the 2-year DESTINATION study.

BACKGROUND: Long-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.

OBJECTIVE: To explore time course of changes in biomarkers and clinical manifestations following treatment cessation after 2 years of tezepelumab treatment.

METHODS: DESTINATION 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.

RESULTS: Of 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.

CONCLUSION: This analysis demonstrates benefits of continued tezepelumab treatment in the management of patients with severe, uncontrolled asthma, compared with stopping treatment after 2 years.