Dupilumab efficacy in subgroups of type 2 asthma with high-dose inhaled corticosteroids at baseline

Abstract

Background and objective: Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key and central drivers of type 2 inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks reduced severe exacerbations, improved pre-bronchodilator forced expiratory volume in 1 s (FEV1), and was generally well tolerated in patients with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed dupilumab efficacy in subpopulations of patients with type 2 asthma and high-dose inhaled corticosteroids (ICS).

Methods: Adjusted annualized severe exacerbation rates over the treatment period, least squares (LS) mean change from baseline at Week 12 in pre-bronchodilator FEV1, and LS mean change from baseline at Week 24 in 5-item Asthma Control Questionnaire (ACQ-5) scores were analyzed in subgroups of patients receiving high-dose (>500 μg) ICS with baseline blood eosinophils ≥150 cells/μL and/or fractional exhaled nitric oxide ≥25 ppb. Subgroups included allergic phenotype (with/without), comorbid chronic rhinosinusitis and/or nasal polyposis (with/without), pre-bronchodilator FEV1/forced vital capacity (<70%/≥70%), blood eosinophil level, exacerbation history, median baseline pre-bronchodilator FEV1, age at asthma onset (≤40/>40 years), median FEV1 reversibility, body mass index (<30/≥30 kg/m2), and sex.

Results: Dupilumab vs placebo reduced exacerbations and improved pre-bronchodilator FEV1 at Week 12 and ACQ-5 at Week 24 across subgroups of patients with type 2 asthma and high-dose ICS at baseline. Dupilumab was also effective in patients receiving medium-dose ICS.

Conclusion: Dupilumab reduced severe exacerbations and improved lung function and asthma control in subgroups of patients with type 2 asthma and high-dose ICS at baseline.

Clinical trial registration number: NCT02414854.

Keywords: Exacerbations; Inhaled corticosteroids; Moderate-to-severe asthma; Pre-bronchodilator FEV(1); Type 2 inflammation.

Conflict of interest statement

Declaration of competing interest Bourdin A: GSK – non-financial support during the conduct of the study; Acceleron Pharma, Actelion, Galapagos, Merck Sharp & Dohme, Nuvaira, Pulmonx, United Therapeutics, Vertex Pharmaceuticals – other; Boehringer Ingelheim – grants, personal fees; AstraZeneca, Chiesi, GSK, Regeneron Pharmaceuticals, Inc., Sanofi – personal fees. Virchow JC: Altana, AstraZeneca, Avontec, Bayer, Bencard Allergie, Bionorica, Boehringer Ingelheim, Chiesi, Essex Pharma Development, GSK, Hexal, Janssen-Cilag, Leti, Meda Pharmaceuticals, Merck, MSD, Mundipharma, Novartis, Nycomed, Pfizer, Revotar Biopharmaceuticals, Sandoz, Stallergenes Greer, Schwarz Pharma, Teva, UCB, Zydus Cadila – honoraria. Avontec, Boehringer Ingelheim, Chiesi, Essex Pharma Development, GSK, Hexal, Janssen-Cilag, Meda Pharmaceuticals, MSD, Mundipharma, Novartis, Regeneron Pharmaceuticals, Inc., Revotar Biopharmaceuticals, Roche, sanofi-aventis, Sandoz, Schwarz Pharma, Teva, UCB – advisory board participant. Deutsche Forschungsgesellschaft, GSK, Land Mecklenburg-Vorpommern, MSD – research grants. Papi A: AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Teva – report grants, personal fees, nonfinancial support, other; Menarini, Novartis, Zambon – personal fees, nonfinancial support; Sanofi – grants (all outside the submitted work). Lugogo NL: Amgen, AstraZeneca, Avillion, Genentech, Gossamer Bio, GSK, Regeneron Pharmaceuticals, Inc., Sanofi, Teva − research support paid to institution; Amgen, AstraZeneca, Genentech, GSK, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi, Teva − advisory board member, consultant; AstraZeneca – travel support; AstraZeneca, GSK – honoraria for non-speaker's bureau presentations. Bardin P: AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Sanofi – consultant, speaker fees. Antila M: AbbVie, Angion Biomedica Corp, AstraZeneca, BeiGene, EMS, Eurofarma, GSK, Humanigen, Janssen, Novartis, Sanofi – clinical trial funding; Aché, AstraZeneca, Chiesi, Eurofarma, IPI ASAC Brasil, Sanofi – honoraria; AstraZeneca, GSK, Novartis, Sanofi – meeting or travel support; Abbott, AstraZeneca, Chiesi, Sanofi, Zambon – data safety monitoring board and/or advisory board member. Halpin DMG: AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GSK, Novartis, Pfizer, Sandoz, Sanofi – advisory board member, speaker fees. Daizadeh N: Sanofi – former employee, may hold stock and/or stock options in the company. Djandji M, Jacob-Nara JA, Rowe PJ: Sanofi − employees, may hold stock and/or stock options in the company. Ortiz B: Regeneron – former employee, may hold stock and/or stock options in the company. Gall R, Deniz Y: Regeneron Pharmaceuticals, Inc. – employees and shareholders.

Copyright © 2022. Published by Elsevier Ltd.