Dupilumab on Airway Hyper-responsiveness and Ventilation Heterogeneity in Patients With Asthma.

Summary

In asthmatics with airway hyperresponsiveness and a "T2 immune signature" (type 2), Dupilumab will suppress airway hyperresponsiveness (assessed by methacholine PC20 ≤ 4 mg/mL (PC20: provocative concentration causing a 20% fall in FEV1) OR ≥15% decreased in forced expired volume in 1 second (FEV1) during saline inhalation for sputum induction OR ≥25% improvement in FEV1 after bronchodilator) and airway eosinophilia (assessed by sputum eosinophils) and this will be associated with greater asthma control and improved ventilation heterogeneity.

Timeline

Start

2019-07-01

Primary completion

2022-10-12

Completion

2023-01-17

Publications

• Background Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, Donaldson DD. Interleukin-13: central mediator of allergic asthma. Science. 1998 Dec 18;282(5397):2258-61. doi: 10.1126/science.282.5397.2258.
• Background Svenningsen S, Kirby M, Starr D, Leary D, Wheatley A, Maksym GN, McCormack DG, Parraga G. Hyperpolarized (3) He and (129) Xe MRI: differences in asthma before bronchodilation. J Magn Reson Imaging. 2013 Dec;38(6):1521-30. doi: 10.1002/jmri.24111. Epub 2013 Apr 15.
• Background Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD, Cockcroft DW, Fish JE, Sterk PJ. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 2000 Jan;161(1):309-29. doi: 10.1164/ajrccm.161.1.ats11-99. No abstract available.
• Svenningsen S, Kjarsgaard M, Haider E, Venegas C, Konyer N, Friedlander Y, Nasir N, Boylan C, Kirby M, Nair P. Effects of Dupilumab on Mucus Plugging and Ventilation Defects in Patients with Moderate-to-Severe Asthma: A Randomized, Double-Blind, Placebo-Controlled Trial. Am J Respir Crit Care Med. 2023 Nov 1;208(9):995-997. doi: 10.1164/rccm.202306-1102LE. No abstract available.

Drugs

Indications