TY - JOUR
T1 - Predictors of treatment REsponse to inhaled corticosteroids (ICS) in Chronic Obstructive pulmonary disease
T2 - Randomised controlled trials individual participant Data re-Evaluation-protocol of the ICS-RECODE individual participant data meta-analysis
AU - ICS-RECODE group
AU - Bate, Sebastian
AU - Fortescue, Rebecca
AU - Fullwood, Catherine
AU - Sperrin, Matthew
AU - Simmonds, Mark
AU - Fally, Markus
AU - Hansel, Jan
AU - Miligkos, Michael
AU - Manohar, Sinduja
AU - Howlett, Emily
AU - Linnell, John
AU - Preston, Alan
AU - Woodcock, Ashley A
AU - Singh, Dave
AU - Stewart, Lesley
AU - Vestbo, Joergen
AU - Mathioudakis, Alexander G
N1 - © Author(s) (or their employer(s)) 2025.
PY - 2025/3/5
Y1 - 2025/3/5
N2 - INTRODUCTION: Inhaled corticosteroids (ICS) can improve clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and eosinophilic airway inflammation, but they also increase the risk of side effects like pneumonia. Blood eosinophils guide ICS use, though evidence is limited. The predictors of treatment REsponse to ICS in COPD: a randomised controlled trials (RCTs) individual participant Data re-Evaluation (ICS-RECODE) research programme will leverage data from large RCTs to identify patients who benefit most from ICS with minimal risk. This protocol details an individual participant data (IPD) meta-analysis, assessing ICS safety, efficacy and treatment×covariate interactions to identify predictors of treatment response.METHODS AND ANALYSIS: This meta-analysis will adhere to Cochrane, IPD handbook and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance. We will conduct a two-stage IPD meta-analysis of RCTs evaluating the addition of ICS to maintenance COPD treatments. Only RCTs with at least 500 participants across all eligible arms will be included, to allow for treatment×covariate interaction evaluation. Primary outcomes are severe and moderate or severe exacerbation rates; secondary outcomes assess both safety and efficacy. Data from each RCT will be reanalysed using rigorous, consistent statistical methods. Treatment×covariate interactions will be assessed at the RCT level. Trial treatment effects and the coefficients of treatment×covariate interaction analyses will be pooled using random effects model meta-analysis. Risk of bias will be appraised using RoB-2 informed by IPD, and certainty of evidence will be assessed with GRADE and the Instrument to assess the Credibility of Effect Modification Analyses.The ICS-RECODE IPD meta-analysis will make use of the best available data to define evidence-based, precision medicine approaches for ICS use in COPD.ETHICS AND DISSEMINATION: The Health Research Authority approved the ICS-RECODE study, exempting it from ethics review (HRA UK, Reference: 24/HRA/0460). Our findings will be published in peer-reviewed journals and shared with the scientific and broader stakeholder communities.PROSPERO REGISTRATION NUMBER: CRD42024508286.
AB - INTRODUCTION: Inhaled corticosteroids (ICS) can improve clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and eosinophilic airway inflammation, but they also increase the risk of side effects like pneumonia. Blood eosinophils guide ICS use, though evidence is limited. The predictors of treatment REsponse to ICS in COPD: a randomised controlled trials (RCTs) individual participant Data re-Evaluation (ICS-RECODE) research programme will leverage data from large RCTs to identify patients who benefit most from ICS with minimal risk. This protocol details an individual participant data (IPD) meta-analysis, assessing ICS safety, efficacy and treatment×covariate interactions to identify predictors of treatment response.METHODS AND ANALYSIS: This meta-analysis will adhere to Cochrane, IPD handbook and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance. We will conduct a two-stage IPD meta-analysis of RCTs evaluating the addition of ICS to maintenance COPD treatments. Only RCTs with at least 500 participants across all eligible arms will be included, to allow for treatment×covariate interaction evaluation. Primary outcomes are severe and moderate or severe exacerbation rates; secondary outcomes assess both safety and efficacy. Data from each RCT will be reanalysed using rigorous, consistent statistical methods. Treatment×covariate interactions will be assessed at the RCT level. Trial treatment effects and the coefficients of treatment×covariate interaction analyses will be pooled using random effects model meta-analysis. Risk of bias will be appraised using RoB-2 informed by IPD, and certainty of evidence will be assessed with GRADE and the Instrument to assess the Credibility of Effect Modification Analyses.The ICS-RECODE IPD meta-analysis will make use of the best available data to define evidence-based, precision medicine approaches for ICS use in COPD.ETHICS AND DISSEMINATION: The Health Research Authority approved the ICS-RECODE study, exempting it from ethics review (HRA UK, Reference: 24/HRA/0460). Our findings will be published in peer-reviewed journals and shared with the scientific and broader stakeholder communities.PROSPERO REGISTRATION NUMBER: CRD42024508286.
KW - Humans
KW - Pulmonary Disease, Chronic Obstructive/drug therapy
KW - Administration, Inhalation
KW - Randomized Controlled Trials as Topic
KW - Adrenal Cortex Hormones/administration & dosage
KW - Treatment Outcome
KW - Research Design
KW - Meta-Analysis as Topic
KW - Systematic Reviews as Topic
UR - http://www.scopus.com/inward/record.url?scp=86000629180&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2024-095541
DO - 10.1136/bmjopen-2024-095541
M3 - Article
C2 - 40044194
SN - 2044-6055
VL - 15
JO - BMJ Open
JF - BMJ Open
IS - 3
M1 - e095541
ER -