A Randomized Trial of a Composite T2-Biomarker Strategy Adjusting Corticosteroid Treatment in Severe Asthma: A Post Hoc Analysis by Sex.


Journal

The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220

Informations de publication

Date de publication:
04 2023
Historique:
received: 15 06 2022
revised: 06 12 2022
accepted: 14 12 2022
medline: 11 4 2023
pubmed: 10 1 2023
entrez: 9 1 2023
Statut: ppublish

Résumé

Approximately 5% to 10% of patients with asthma have severe disease, with a consistent preponderance in females. Current asthma guidelines recommend stepwise treatment to achieve symptom control with no differential treatment considerations for either sex. To examine whether patient sex affects outcomes when using a composite T2-biomarker score to adjust corticosteroid (CS) treatment in patients with severe asthma compared with standard care. This is a post hoc analysis, stratifying patient outcomes by sex, of a 48-week, multicenter, randomized controlled clinical trial comparing a biomarker-defined treatment algorithm with standard care. The primary outcome was the proportion of patients with a reduction in CS treatment (inhaled and oral corticosteroids). Secondary outcomes included exacerbation rates, hospital admissions, and lung function. Of the 301 patients randomized, 194 (64.5%) were females and 107 (35.5%) were males. The biomarker algorithm led to a greater proportion of females being on a lower CS dose versus standard care, which was not seen in males (effect estimate: females, 3.57; 95% CI, 1.14-11.18 vs males, 0.54; 95% CI, 0.16-1.80). In T2-biomarker-low females, reducing CS dose was not associated with increased exacerbations. Females scored higher in all domains of the 7-item Asthma Control Questionnaire, apart from FEV1, but with no difference when adjusted for body mass index/anxiety and/or depression. Dissociation between symptoms and T2 biomarkers were noted in both sexes, with a higher proportion of females being symptom high/T2-biomarker low (22.8% vs 15.6%; P = .0002), whereas males were symptom low/T2-biomarker high (22.3% vs 11.4%; P < .0001). This exploratory post hoc analysis identified that females achieved a greater benefit from biomarker-directed CS optimization versus symptom-directed treatment.

Sections du résumé

BACKGROUND
Approximately 5% to 10% of patients with asthma have severe disease, with a consistent preponderance in females. Current asthma guidelines recommend stepwise treatment to achieve symptom control with no differential treatment considerations for either sex.
OBJECTIVE
To examine whether patient sex affects outcomes when using a composite T2-biomarker score to adjust corticosteroid (CS) treatment in patients with severe asthma compared with standard care.
METHODS
This is a post hoc analysis, stratifying patient outcomes by sex, of a 48-week, multicenter, randomized controlled clinical trial comparing a biomarker-defined treatment algorithm with standard care. The primary outcome was the proportion of patients with a reduction in CS treatment (inhaled and oral corticosteroids). Secondary outcomes included exacerbation rates, hospital admissions, and lung function.
RESULTS
Of the 301 patients randomized, 194 (64.5%) were females and 107 (35.5%) were males. The biomarker algorithm led to a greater proportion of females being on a lower CS dose versus standard care, which was not seen in males (effect estimate: females, 3.57; 95% CI, 1.14-11.18 vs males, 0.54; 95% CI, 0.16-1.80). In T2-biomarker-low females, reducing CS dose was not associated with increased exacerbations. Females scored higher in all domains of the 7-item Asthma Control Questionnaire, apart from FEV1, but with no difference when adjusted for body mass index/anxiety and/or depression. Dissociation between symptoms and T2 biomarkers were noted in both sexes, with a higher proportion of females being symptom high/T2-biomarker low (22.8% vs 15.6%; P = .0002), whereas males were symptom low/T2-biomarker high (22.3% vs 11.4%; P < .0001).
CONCLUSIONS
This exploratory post hoc analysis identified that females achieved a greater benefit from biomarker-directed CS optimization versus symptom-directed treatment.

Identifiants

pubmed: 36621603
pii: S2213-2198(22)01332-0
doi: 10.1016/j.jaip.2022.12.019
pii:
doi:

Substances chimiques

Anti-Asthmatic Agents 0
Adrenal Cortex Hormones 0
Biomarkers 0

Types de publication

Randomized Controlled Trial Multicenter Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1233-1242.e5

Subventions

Organisme : Medical Research Council
ID : MR/M016579/1
Pays : United Kingdom

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Matthew C Eastwood (MC)

Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, United Kingdom.

John Busby (J)

Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, United Kingdom.

David J Jackson (DJ)

Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

Ian D Pavord (ID)

Oxford Respiratory NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.

Catherine E Hanratty (CE)

Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, United Kingdom.

Ratko Djukanovic (R)

NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, United Kingdom.

Ashley Woodcock (A)

Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, United Kingdom.

Samantha Walker (S)

Asthma UK, London, United Kingdom.

Timothy C Hardman (TC)

Niche Science & Technology, Richmond, United Kingdom.

Joseph R Arron (JR)

Genentech, Inc, South San Francisco, Calif.

David F Choy (DF)

Genentech, Inc, South San Francisco, Calif.

Peter Bradding (P)

Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.

Chris E Brightling (CE)

Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.

Rekha Chaudhuri (R)

NHS Greater Glasgow and Clyde Health Board, Gartnavel Hospital, Glasgow, United Kingdom; NHS Greater Glasgow and Clyde, Stobhill Hospital, Glasgow, United Kingdom.

Douglas Cowan (D)

NHS Greater Glasgow and Clyde, Stobhill Hospital, Glasgow, United Kingdom.

Adel H Mansur (AH)

University of Birmingham and Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, United Kingdom.

Stephen J Fowler (SJ)

Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, United Kingdom.

Peter Howarth (P)

School of Clinical and Experimental Sciences, University of Southampton, NIHR Southampton Biomedical Research Centre, Southampton, United Kingdom.

James Lordan (J)

The Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.

Andrew Menzies-Gow (A)

Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom.

Timothy Harrison (T)

UK Nottingham Respiratory NIHR Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom.

Douglas S Robinson (DS)

University College Hospitals NHS Foundation Trust, London, United Kingdom.

Cecile T J Holweg (CTJ)

Genentech, Inc, South San Francisco, Calif.

John G Matthews (JG)

Peter Gorer Department of Immunobiology, King's College, London, United Kingdom; 23andMe, Sunnyvale, Calif.

Liam G Heaney (LG)

Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, United Kingdom. Electronic address: l.heaney@qub.ac.uk.

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