Impact of exacerbation history on long-term efficacy of dupilumab in patients with asthma.

Background: The phase 3 QUEST (NCT02414854) and TRAVERSE (NCT02134028) studies demonstrated the efficacy of dupilumab 200/300 mg versus placebo every 2 weeks for 52 weeks (QUEST) and dupilumab 300 mg up to an additional 96 weeks (TRAVERSE) in patients ≥12 years of age with uncontrolled, moderate-to-severe asthma. Overall, safety was consistent with the known dupilumab safety profile. This post hoc analysis assessed long-term dupilumab efficacy for up to 3 years by exacerbation history.
Patients and Methods: Unadjusted annualised severe exacerbation rates (AER) and change from parent study baseline (PSBL) in pre-bronchodilator forced expiratory volume in 1 s (FEV ₁ ) and 5-item Asthma Control Questionnaire (ACQ-5) score were assessed in patients with PSBL eosinophils ≥150 cells·µL ^-1 or fractional exhaled nitric oxide ≥20 ppb and 1 (n=624), 2 (n=344), or ≥3 (n=311) exacerbations in the year before enrolment in QUEST.
Results: In all three groups, dupilumab treatment progressively reduced AER range to 0.17-0.30 during TRAVERSE (Weeks 48-96), increased pre-bronchodilator FEV ₁ range by 0.28-0.49 L by Week 96 and improved asthma control (reduced ACQ-5 score range by 1.51-2.03 by Week 48). For patients who first received dupilumab upon TRAVERSE enrolment, AER decreased, and lung function and asthma control improved rapidly, as was observed upon initiation of dupilumab in QUEST. Dupilumab was efficacious regardless of exacerbation history.
Conclusion: For patients with uncontrolled, moderate-to-severe asthma with elevation of at least one type 2 biomarker, dupilumab treatment provides sustained, long-term reduction of exacerbation rates and improvements in lung function and asthma control irrespective of exacerbation history.
Competing Interests: Conflict of interest: J. Corren reports research grants from and is a consultant for AstraZeneca, Genentech, Novartis, Regeneron Pharmaceuticals Inc. and Sanofi; and speaker fees from AstraZeneca, Genentech and Novartis. C.H. Katelaris is a Principal Investigator of the dupilumab asthma phase 2b (NCT01854047) and phase 3 (NCT02414854) studies for Regeneron Pharmaceuticals Inc. and Sanofi. M. Castro reports research support from the American Lung Association, AstraZeneca, GlaxoSmithKline, NIH, Novartis, PCORI, Pulmatrix, Sanofi-Aventis and Shionogi; is a consultant for Genentech, Novartis, Sanofi-Aventis and Teva; reports speaker fees from AstraZeneca, Genentech, GlaxoSmithKline, Regeneron Pharmaceuticals Inc., Sanofi and Teva; and royalties from Elsevier. J.F. Maspero is a consultant for AstraZeneca and Sanofi; reports speaker fees from GlaxoSmithKline, Menarini, Novartis and Uriach; and research grants from Novartis. M. Humbert reports consultant and speaker fees from AstraZeneca, Chiesi, GlaxoSmithKlein, Novartis and Sanofi. D.M.G. Halpin reports advisory board membership, speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Novartis, Pfizer, Sandoz and Sanofi. A. Altincatal, N. Pandit-Abid, J.A. Jacob-Nara and P.J. Rowe are employees of Sanofi, and may hold stock and/or stock options in the company. X. Soler, A. Radwan and Y. Deniz are employees and shareholders of Regeneron Pharmaceuticals Inc.
(Copyright ©The authors 2023.)