CT Mucus Score and 129Xe MRI Ventilation Defects After 2.5 Years' Anti-IL-5Rα in Eosinophilic Asthma

Marrissa J McIntosh; Harkiran K Kooner; Rachel L Eddy; Angela Wilson; Hana Serajeddini; Anurag Bhalla; Christopher Licskai; Constance A Mackenzie; Cory Yamashita; Grace Parraga

doi:10.1016/j.chest.2023.02.009

CT Mucus Score and ¹²⁹Xe MRI Ventilation Defects After 2.5 Years' Anti-IL-5Rα in Eosinophilic Asthma

Chest. 2023 Jul;164(1):27-38. doi: 10.1016/j.chest.2023.02.009. Epub 2023 Feb 11.

Authors

Affiliations

¹ Robarts Research Institute; Department of Medical Biophysics, Western University, London, ON, Canada.
² University of British Columbia Centre for Heart Lung Innovation, St. Paul's Hospital Vancouver, Vancouver, BC, Canada.
³ Robarts Research Institute.
⁴ Robarts Research Institute; Division of Respirology.
⁵ Division of Respirology.
⁶ Division of Respirology; Division of Clinical Pharmacology and Toxicology, Department of Medicine, Western University, London, ON, Canada.
⁷ Robarts Research Institute; Department of Medical Biophysics, Western University, London, ON, Canada; Division of Respirology. Electronic address: gparraga@uwo.ca.

PMID: 36781102
DOI: 10.1016/j.chest.2023.02.009

Abstract

Background: We previously showed in patients with poorly controlled eosinophilic asthma that a single dose of benralizumab resulted in significantly improved Asthma Control Questionnaire (ACQ-6) score and ¹²⁹Xe MRI ventilation defect percent (VDP) 28 days postinjection, and ¹²⁹Xe MRI VDP and CT airway mucus occlusions were shown to independently predict this early ACQ-6 response to benralizumab.

Research question: Do early VDP responses at 28 days persist, and do FEV₁, fractional exhaled nitric oxide, and mucus plug score improve during a 2.5 year treatment period?

Study design and methods: Participants with poorly controlled eosinophilic asthma completed spirometry, ACQ-6, and MRI, 28 days, 1 year, and 2.5 years after initiation of treatment with benralizumab; chest CT was acquired at enrollment and 2.5 years later.

Results: Of 29 participants evaluated at 28 days post-benralizumab, 16 participants returned for follow-up while on therapy at 1 year, and 13 participants were evaluable while on therapy at 2.5 years post-benralizumab initiation. As compared with 28 days post-benralizumab, ACQ-6 score (2.0 ± 1.4) significantly improved after 1 year (0.5 ± 0.6, P = .02; 95% CI, 0.1-1.1) and 2.5 years (0.5 ± 0.5, P = .03; 95% CI, 0.1-1.1). The mean VDP change at 2.5 years (-4% ± 3%) was greater than the minimal clinically important difference, but not significantly different from VDP measured 28 days post-benralizumab. Mucus score (3 ± 4) was significantly improved at 2.5 years (1 ± 1, P = .03; 95% CI, 0.3-5.5). In six of eight participants with previous occlusions, mucus plugs vanished or substantially diminished 2.5 years later. VDP (P < .001) and mucus score (P < .001) measured at baseline, but not fractional exhaled nitric oxide or FEV₁, independently predicted ACQ-6 score after 2.5 years.

Interpretation: In poorly controlled eosinophilic asthma, early MRI VDP responses at 28 days post-benralizumab persisted 2.5 years later, alongside significantly improved mucus scores and asthma control.

Trial registration: ClinicalTrials.gov NCT03733535 NCT02351141.

Keywords: (129)Xe MRI; airway occlusions; benralizumab; eosinophilic asthma; mucus score.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Airway Obstruction*
Anti-Asthmatic Agents* / therapeutic use
Asthma* / diagnostic imaging
Asthma* / drug therapy
Humans
Magnetic Resonance Imaging / methods
Mucus
Nitric Oxide
Pulmonary Eosinophilia* / drug therapy
Tomography, X-Ray Computed

Substances

Nitric Oxide
Anti-Asthmatic Agents

Associated data

ClinicalTrials.gov/NCT03733535
ClinicalTrials.gov/NCT02351141

Grants and funding

CIHR/Canada