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.

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Conflicts of interest Christopher E. Brightling has received grants and consultancy fees from 4D Pharma, AstraZeneca, Chiesi, Genentech, GSK, Global Access Diagnostics (formerly Mologic), Novartis, Regeneron Pharmaceuticals, Roche and Sanofi. Marco Caminati has received fees from AstraZeneca for serving on advisory boards and has received speaker fees from GSK and Sanofi. Jean-Pierre Llanos and Scott Caveney are employees of Amgen and own stock in Amgen. Ales Kotalik, Anna Lundahl, Monika Gołąbek, Neil Martin and Sandhia Ponnarambil are employees of AstraZeneca and may own stock or stock options in AstraZeneca. Janet M. Griffiths was an employee of AstraZeneca at the time of the study. Elliot Israel has served as a consultant to and received personal fees from 4D Pharma, AB Science, Amgen, AstraZeneca, Avillion, Biometry, Cowen, Equillium, Genentech, GSK, Merck, Novartis, Pneuma Respiratory, PPS Health, Regeneron Pharmaceuticals, Sanofi, Sienna Biopharmaceuticals and Teva Pharmaceuticals; has received nonfinancial support from Circassia Pharmaceuticals, Teva Pharmaceuticals and Vorso Corp; and has received clinical research grants from AstraZeneca, Avillion, Genentech, Gossamer Bio, Novartis and Sanofi. Ian D. Pavord has received speaker fees from Aerocrine AB, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Regeneron Pharmaceuticals, Sanofi and Teva Pharmaceuticals; has received payments for organization of educational events from AstraZeneca, GSK, Regeneron Pharmaceuticals, Sanofi and Teva Pharmaceuticals; has received consultancy fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia Pharmaceuticals, Dey Pharma, Genentech, GSK, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, RespiVert, Sanofi, Schering-Plough and Teva Pharmaceuticals; has received international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Napp Pharmaceuticals, Regeneron Pharmaceuticals, Sanofi and Teva Pharmaceuticals; and has received a research grant from Chiesi. Michael E. Wechsler is an employee of National Jewish Health and has received consultancy fees from AstraZeneca, Equillium, Genentech, GSK, Novartis, Regeneron Pharmaceuticals, resTORbio, Sanofi and Teva Pharmaceuticals. Celeste Porsbjerg has received grants and consultancy fees from ALK-Abelló, AstraZeneca, Chiesi, GSK, Novartis, Sanofi and Teva Pharmaceuticals. Jonathan Corren has received grants and personal fees from AstraZeneca, Genentech and Vectura, and has received grants from Optinose, Sanofi and Teva Pharmaceuticals.