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 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.
Conclusion: 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.
Trial Registration: ClinicalTrials.gov Identifier: NCT03706079.
Competing Interests: Disclosures Prof Brightling has received grants and consultancy fees from 4D Pharma, Areteia Therapeutics, AstraZeneca, Chiesi, Genentech, GSK, Global Access Diagnostics (formerly Mologic), Novartis, Regeneron Pharmaceuticals, Roche, and Sanofi. Dr Caminati has received fees from AstraZeneca for serving on advisory boards and has received speaker fees from GSK and Sanofi. Dr Llanos and Dr Caveney are employees of Amgen and own stock in Amgen. Dr Kotalik, Dr Lundahl, Ms Gołąbek, Dr Martin, and Dr Ponnarambil are employees of AstraZeneca and may own stock or stock options in AstraZeneca. Dr Griffiths was an employee of AstraZeneca at the time of the study. Prof 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. Prof 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. Prof Wechsler has received consulting, advisory or speaker fees from Amgen, Areteia Therapeutics, AstraZeneca, Avalo Therapeutics, Boehringer Ingelheim, Celldex Therapeutics, Cellergy Pharma, Cerecor, CytoReason, Eli Lilly, Equillium, GSK, Incyte, Kinaset Therapeutics, Merck, Novartis, Om Pharma, Overtone Therapeutics/Foresite Labs, Phylaxis Bioscience, PULMATRiX, Rapt Therapeutics, Regeneron Pharmaceuticals, Roche/Genentech, Sanofi/Genzyme, Sentien Biotechnologies, Sound Biologics, Tetherex Pharmaceuticals, Teva Pharmaceuticals, Upstream Bio and Verona Pharma. Prof Porsbjerg has received grants and consultancy fees from ALK-Abelló, AstraZeneca, Chiesi, GSK, Novartis, Sanofi, and Teva Pharmaceuticals. Dr Corren has received grants and personal fees from AstraZeneca, Genentech, and Vectura; and has received grants from Optinose, Sanofi, and Teva Pharmaceuticals.
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