{Reference Type}: Journal Article
{Title}: Biomarkers and clinical outcomes after tezepelumab cessation: Extended follow-up from the 2-year DESTINATION study.
{Author}: Brightling CE;Caminati M;Llanos JP;Caveney S;Kotalik A;Griffiths JM;Lundahl A;Israel E;Pavord ID;Wechsler ME;Porsbjerg C;Corren J;Gołąbek M;Martin N;Ponnarambil S;
{Journal}: Ann Allergy Asthma Immunol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Apr 30
{Factor}: 6.248
{DOI}: 10.1016/j.anai.2024.04.031
{Abstract}: 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 the time course of changes in biomarkers and clinical manifestations after treatment cessation after 2 years of tezepelumab treatment.
METHODS: DESTINATION was a 2-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 period from weeks 104 to 140. Change over time in key biomarkers and clinical outcomes were assessed in tezepelumab vs placebo recipients for 40 weeks after stopping treatment.
RESULTS: Of 569 patients enrolled in the extended follow-up period, 426 were included in the analysis (289 received tezepelumab and 137 placebo). In the 40-week period after the last tezepelumab dose, blood eosinophil counts, fractional exhaled nitric oxide levels, and Asthma Control Questionnaire-6 scores gradually increased from weeks 4 to 10, with a gradual reduction in pre-bronchodilator forced expiratory volume in 1 second such that blood eosinophil counts, fractional exhaled nitric oxide levels, and clinical outcomes returned to placebo levels; however, none of these outcomes returned to baseline levels. Total IgE levels increased later from week 28 and remained well below placebo and baseline levels during the 40-week period after the last tezepelumab dose.
CONCLUSIONS: This analysis reveals the benefits of continued tezepelumab treatment in the management of patients with severe, uncontrolled asthma, compared with stopping treatment after 2 years.
BACKGROUND: ClinicalTrials.gov Identifier: NCT03706079.