Type-2 biomarker elevation across asthma treatment steps in the ORACLE patient-level meta-analysis of all-comer trials

<bold>Rationale:</bold> The relationship between asthma treatment step and prevalence of raised blood eosinophil counts (BEC) and exhaled nitric oxide (FeNO) is unclear. <bold>Aim:</bold> To assess the proportion of trial patients with raised baseline BEC and FeNO across asthma treatment steps. <bold>Methods:</bold> We included participants from the control arms of 13 randomised controlled asthma trials not enriching for biomarkers (Novel START, PRACTICAL, CAPTAIN, Dupilumab phase 2b, LAVOLTA 1-2, LUTE-VERSE, MILLY, PACT, QUEST, STRATOS 1-2; all part of the OxfoRd Asthma attaCk risk scaLE (ORACLE) patient-level meta-analysis). Proportions of patients were tabulated for baseline BEC×FeNO categories per treatment step. A proportion test assessed differences in biomarker prevalence across steps in 10 imputed datasets. <bold>Results:</bold> 4292 patients were included. Raised biomarkers occurred significantly more in mild asthma (Fig). Baseline BEC and FeNO elevation (≥0.3×109/L and ≥50 ppb) was observed in n=61/315 (27%) of step 1, 63/315 (20%) of step 2, 50/846 (6%) of step 3, 175/1635 (11%) of step 4, and 158/1271 (12%) of step 5 populations (p<2.2E-16). <bold>Conclusion:</bold> In unselected clinical trial populations, BEC and FENO elevation is seen more often in less intensely treated asthma. These results highlight the complexity between type-2 biomarker status, treatment, and clinical impact. <bold>Prospero:</bold> CRD42021245337; <bold>Funding:</bold> NIHR, QRHRN, FRQS, APQ, SAB, LUF <fig><object-id>erj;64/suppl_68/PA1210/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

Authors

Institutions

Publication Details

Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.pa1210
Primary Topic
Delphi Technique in Research
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Type-2 biomarker elevation across asthma treatment steps in the ORACLE patient-level meta-analysis of all-comer trials

C.A. Celis-Preciado, Jacob K. Sont, Neil A. Martin, Jonathan Corren et al.
Delphi Technique in Research
article

Type-2 biomarker elevation across asthma treatment steps in the ORACLE patient-level meta-analysis of all-comer trials

C.A. Celis-Preciado, Jacob K. Sont, Neil A. Martin, Jonathan Corren, Nicola A. Hanania, Sanjay Ramakrishnan, Mario Castro, Timothy Hinks, Fleur L. Meulmeester, Emilio Santoro, Guy Bruselle, Megan Hardin, Christopher Edward Brightling, Annette Laugerud, Jo Hardy, D. J. Jackson, Richard Beasley, Michael Wechsler, Cécile Holweg, Sarah Diver, Simon Couillard, Xavier Jaumont, Ian Pavord, Ewout W. Steyerberg, Deborah Clarke, Chris Compton
article en

Abstract

<bold>Rationale:</bold> The relationship between asthma treatment step and prevalence of raised blood eosinophil counts (BEC) and exhaled nitric oxide (FeNO) is unclear. <bold>Aim:</bold> To assess the proportion of trial patients with raised baseline BEC and FeNO across asthma treatment steps. <bold>Methods:</bold> We included participants from the control arms of 13 randomised controlled asthma trials not enriching for biomarkers (Novel START, PRACTICAL, CAPTAIN, Dupilumab phase 2b, LAVOLTA 1-2, LUTE-VERSE, MILLY, PACT, QUEST, STRATOS 1-2; all part of the OxfoRd Asthma attaCk risk scaLE (ORACLE) patient-level meta-analysis). Proportions of patients were tabulated for baseline BEC×FeNO categories per treatment step. A proportion test assessed differences in biomarker prevalence across steps in 10 imputed datasets. <bold>Results:</bold> 4292 patients were included. Raised biomarkers occurred significantly more in mild asthma (Fig). Baseline BEC and FeNO elevation (≥0.3×109/L and ≥50 ppb) was observed in n=61/315 (27%) of step 1, 63/315 (20%) of step 2, 50/846 (6%) of step 3, 175/1635 (11%) of step 4, and 158/1271 (12%) of step 5 populations (p<2.2E-16). <bold>Conclusion:</bold> In unselected clinical trial populations, BEC and FENO elevation is seen more often in less intensely treated asthma. These results highlight the complexity between type-2 biomarker status, treatment, and clinical impact. <bold>Prospero:</bold> CRD42021245337; <bold>Funding:</bold> NIHR, QRHRN, FRQS, APQ, SAB, LUF <fig><object-id>erj;64/suppl_68/PA1210/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

AstraZeneca (United Kingdom) (GB), North Bristol NHS Trust (GB), Université de Sherbrooke (CA), University of Leicester (GB), University of California, Los Angeles (US), The University of Western Australia (AU), Baylor College of Medicine (US), GlaxoSmithKline (United Kingdom) (GB), Guy's and St Thomas' NHS Foundation Trust (GB), Leiden University Medical Center (NL), Ghent University Hospital (BE), National Jewish Health (US), University of Oxford (GB), AVEO Oncology (United States) (US), Acentech (United States) (US), Prognos (Switzerland) (CH), University of Kansas Medical Center (US), Medical Research Institute of New Zealand (NZ), Science Oxford (GB), University of Colorado Denver (US)
Zero hunger
Openalex Percentile: Top 69%
Delphi Technique in Research
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.