Dupilumab Efficacy in Uncontrolled, Moderate-to-Severe Asthma with Self-Reported Chronic Rhinosinusitis

Jorge F. Maspero*, Constance H. Katelaris, William W. Busse, Mario Castro, Jonathan Corren, Bradley E. Chipps, Anju T. Peters, Ian D. Pavord, Linda B. Ford, Lawrence Sher, Klaus F. Rabe, Megan S. Rice, Paul Rowe, Yufang Lu, Sivan Harel, Alexandre Jagerschmidt, Asif H. Khan, Siddhesh Kamat, Gianluca Pirozzi, Nikhil AminMarcella Ruddy, Neil M.H. Graham, Leda P. Mannent, Ariel Teper

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13 signaling, key drivers of type 2 inflammation. In the phase 3 study (NCT02414854), add-on dupilumab 200 mg/300 mg every 2 weeks, versus placebo, significantly reduced severe asthma exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) and quality-of-life measures in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in those with a high baseline type 2 phenotype. Objective: To assess the efficacy and safety of dupilumab in patients with uncontrolled, moderate-to-severe asthma with or without self-reported comorbid chronic rhinosinusitis (CRS or non-CRS). Methods: Comorbid CRS was self-reported by patients using an e-diary. Annualized severe exacerbation rates, changes from baseline in pre- and post-bronchodilator FEV1, patient-reported outcomes, type 2 biomarkers, and safety were assessed. Results: CRS was self-reported by 382 of 1902 (20.1%) patients. Dupilumab 200 mg/300 mg reduced annualized severe exacerbation rates by 63%/61%, respectively, in patients with CRS, and by 42%/40% in patients without CRS (all P < .001 vs placebo). Dupilumab also improved lung function and patient-reported asthma control and quality of life, and suppressed type 2 biomarkers versus placebo in both subgroups. Clinical responses were rapid, with near-maximal responses observed at the earliest measured time points and sustained at week 52. Improvements observed in the CRS subgroup were similar to or numerically greater than those in the non-CRS subgroup. Conclusion: Dupilumab showed efficacy and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma with or without CRS.

Original languageEnglish (US)
Pages (from-to)527-539.e9
JournalJournal of Allergy and Clinical Immunology: In Practice
Volume8
Issue number2
DOIs
StatePublished - Feb 2020

Keywords

  • Anti-IL-13
  • Anti-IL-4
  • Asthma
  • Chronic rhinosinusitis
  • Dupilumab
  • Efficacy
  • Safety

ASJC Scopus subject areas

  • Immunology and Allergy

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    Maspero, J. F., Katelaris, C. H., Busse, W. W., Castro, M., Corren, J., Chipps, B. E., Peters, A. T., Pavord, I. D., Ford, L. B., Sher, L., Rabe, K. F., Rice, M. S., Rowe, P., Lu, Y., Harel, S., Jagerschmidt, A., Khan, A. H., Kamat, S., Pirozzi, G., ... Teper, A. (2020). Dupilumab Efficacy in Uncontrolled, Moderate-to-Severe Asthma with Self-Reported Chronic Rhinosinusitis. Journal of Allergy and Clinical Immunology: In Practice, 8(2), 527-539.e9. https://doi.org/10.1016/j.jaip.2019.07.016