Background

In the phase 3 DESTINATION (NCT03706079) study, long-term tezepelumab treatment resulted in reduced exacerbations, and improvements in lung function and symptom control, and reduced inflammatory biomarkers in patients with severe, uncontrolled asthma.

Objective
To explore the effects of tezepelumab cessation after 2 years of treatment (210 mg every 4 weeks).

Methods
DESTINATION was a multicentre, randomized, placebo-controlled, double-blind, extension study of patients (12?80 years old) who completed NAVIGATOR (NCT03347279) or SOURCE (NCT03406078). After tezepelumab cessation at week 104, patients who initially enrolled in NAVIGATOR could enter a 36-week off-treatment extended follow-up. Change over time in Asthma Control Questionnaire (ACQ)-6 score, blood eosinophils count (BEC), fractional exhaled nitric oxide (FeNO) levels and pre-bronchodilator (BD) FEV1 was assessed.

Results

Overall, 569 patients entered the extended follow-up. From week 110, ACQ-6 score increased, and BEC and FeNO levels gradually increased in parallel with pre-BD FEV1 reductions. All measures continued to worsen over the extended follow-up, but did not return to baseline 36 weeks post treatment cessation (Figure).

Conclusion

Biomarker suppression and improved clinical outcomes in patients gradually waned after cessation of tezepelumab, although, on average, none returned to baseline during the extended follow-up.