Step up to triple therapy versus switch to dual bronchodilator therapy in patients with COPD on an inhaled corticosteroid/long-acting β2-agonist: post-hoc analyses of KRONOS
Abstract Background In people with chronic obstructive pulmonary disease (COPD) on inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) therapy, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends stepping up to ICS/long-acting muscarinic antagonist (LAMA)/long-acting β2...
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BMC
2025-05-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-025-03234-5 |
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| author | Dave Singh Mona Bafadhel Niki Arya Jonathan Marshall Himanshu Parikh Dobrawa Kisielewicz Charlotta Movitz Karin Bowen Mehul Patel |
| author_facet | Dave Singh Mona Bafadhel Niki Arya Jonathan Marshall Himanshu Parikh Dobrawa Kisielewicz Charlotta Movitz Karin Bowen Mehul Patel |
| author_sort | Dave Singh |
| collection | DOAJ |
| description | Abstract Background In people with chronic obstructive pulmonary disease (COPD) on inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) therapy, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends stepping up to ICS/long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) in those with exacerbations or switching to LAMA/LABA in those with major symptoms. However, the effect of stepping up to ICS/LAMA/LABA versus switching to LAMA/LABA on exacerbation risk is unclear. This analysis evaluated the effect of escalating to ICS/LAMA/LABA versus switching to LAMA/LABA or staying on ICS/LABA on lung function and exacerbation rates in symptomatic individuals with COPD without a recent exacerbation history from KRONOS. Methods In KRONOS (NCT02497001), symptomatic participants with moderate-to-very severe COPD (exacerbations in the prior year were not required for inclusion) were randomized to budesonide/glycopyrronium/formoterol fumarate dihydrate 320/14.4/10 μg (BGF), glycopyrronium/formoterol fumarate dihydrate 14.4/10 μg (GFF), budesonide/formoterol fumarate dihydrate 320/10 μg (BFF) via metered-dose inhaler, or budesonide/formoterol fumarate dihydrate 400/12 μg via dry-powder inhaler (BUD/FORM) for 24 weeks. In participants without a recent exacerbation history on ICS/LABA in the 30 days before screening, morning pre-dose trough FEV1 change from baseline and moderate/severe exacerbation rates over 24 weeks were analyzed post-hoc using linear repeated measures models and negative binomial regression, respectively, and participants escalated to ICS/LAMA/LABA (BGF) were compared with those switching to LAMA/LABA (GFF) or staying on ICS/LABA (BFF or BUD/FORM). Results On stepping up to BGF, least square means (95% confidence interval [CI]) differences for morning pre-dose trough FEV1 change from baseline over 24 weeks was similar versus switching to GFF (12 [–21, 44] mL) but greater versus staying on ICS/LABA (BGF vs. BFF, 106 [64, 148] mL; BGF vs. BUD/FORM, 55 [12, 97] mL). Moderate/severe exacerbations were experienced by participants in all treatment arms (BGF, 14.9%; GFF, 24.0%; BFF 17.6%; BUD/FORM, 21.2%). Exacerbation risk was reduced when stepping up to BGF versus switching to GFF (rate ratio [95% CI]: 0.57 [0.35, 0.94]); rate ratios (95% CI) for BGF versus remaining on ICS/LABA were 0.93 (0.47, 1.82) with BFF and 0.62 (0.33, 1.18) with BUD/FORM. Conclusions People with symptomatic COPD and no recent exacerbation history previously on ICS/LABA had reduced exacerbation risk after escalating to ICS/LAMA/LABA versus switching to LAMA/LABA, and improved lung function versus staying on ICS/LABA. Trial registration ClinicalTrials.gov registry number NCT02497001 (registration date, 7 July 2015). |
| format | Article |
| id | doaj-art-d6c2bf8176f444d2b0f3371ef2aeb8c3 |
| institution | OA Journals |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | Respiratory Research |
| spelling | doaj-art-d6c2bf8176f444d2b0f3371ef2aeb8c32025-08-20T02:03:32ZengBMCRespiratory Research1465-993X2025-05-012611910.1186/s12931-025-03234-5Step up to triple therapy versus switch to dual bronchodilator therapy in patients with COPD on an inhaled corticosteroid/long-acting β2-agonist: post-hoc analyses of KRONOSDave Singh0Mona Bafadhel1Niki Arya2Jonathan Marshall3Himanshu Parikh4Dobrawa Kisielewicz5Charlotta Movitz6Karin Bowen7Mehul Patel8Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Hospitals TrustKing’s Centre for Lung Health, School of Immunology and Microbial Sciences, Faculty of Life Science and Medicine, King’s College LondonRespiratory and Immunology, Biometrics, BioPharmaceuticals R&D, AstraZenecaGlobal Medical Affairs - Respiratory, BioPharmaceuticals Medical, AstraZenecaRespiratory and Immunology, Clinical Development, BioPharmaceuticals R&D, AstraZenecaRespiratory and Immunology, Clinical Development, Biopharmaceuticals R&D, AstraZenecaRespiratory and Immunology, Biometrics, BioPharmaceuticals R&D, AstraZenecaRespiratory and Immunology, Biometrics, BioPharmaceuticals R&D, AstraZenecaRespiratory and Immunology, Clinical Development, BioPharmaceuticals R&D, AstraZenecaAbstract Background In people with chronic obstructive pulmonary disease (COPD) on inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) therapy, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends stepping up to ICS/long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) in those with exacerbations or switching to LAMA/LABA in those with major symptoms. However, the effect of stepping up to ICS/LAMA/LABA versus switching to LAMA/LABA on exacerbation risk is unclear. This analysis evaluated the effect of escalating to ICS/LAMA/LABA versus switching to LAMA/LABA or staying on ICS/LABA on lung function and exacerbation rates in symptomatic individuals with COPD without a recent exacerbation history from KRONOS. Methods In KRONOS (NCT02497001), symptomatic participants with moderate-to-very severe COPD (exacerbations in the prior year were not required for inclusion) were randomized to budesonide/glycopyrronium/formoterol fumarate dihydrate 320/14.4/10 μg (BGF), glycopyrronium/formoterol fumarate dihydrate 14.4/10 μg (GFF), budesonide/formoterol fumarate dihydrate 320/10 μg (BFF) via metered-dose inhaler, or budesonide/formoterol fumarate dihydrate 400/12 μg via dry-powder inhaler (BUD/FORM) for 24 weeks. In participants without a recent exacerbation history on ICS/LABA in the 30 days before screening, morning pre-dose trough FEV1 change from baseline and moderate/severe exacerbation rates over 24 weeks were analyzed post-hoc using linear repeated measures models and negative binomial regression, respectively, and participants escalated to ICS/LAMA/LABA (BGF) were compared with those switching to LAMA/LABA (GFF) or staying on ICS/LABA (BFF or BUD/FORM). Results On stepping up to BGF, least square means (95% confidence interval [CI]) differences for morning pre-dose trough FEV1 change from baseline over 24 weeks was similar versus switching to GFF (12 [–21, 44] mL) but greater versus staying on ICS/LABA (BGF vs. BFF, 106 [64, 148] mL; BGF vs. BUD/FORM, 55 [12, 97] mL). Moderate/severe exacerbations were experienced by participants in all treatment arms (BGF, 14.9%; GFF, 24.0%; BFF 17.6%; BUD/FORM, 21.2%). Exacerbation risk was reduced when stepping up to BGF versus switching to GFF (rate ratio [95% CI]: 0.57 [0.35, 0.94]); rate ratios (95% CI) for BGF versus remaining on ICS/LABA were 0.93 (0.47, 1.82) with BFF and 0.62 (0.33, 1.18) with BUD/FORM. Conclusions People with symptomatic COPD and no recent exacerbation history previously on ICS/LABA had reduced exacerbation risk after escalating to ICS/LAMA/LABA versus switching to LAMA/LABA, and improved lung function versus staying on ICS/LABA. Trial registration ClinicalTrials.gov registry number NCT02497001 (registration date, 7 July 2015).https://doi.org/10.1186/s12931-025-03234-5Chronic obstructive pulmonary diseaseExacerbationsLung functionTriple therapy |
| spellingShingle | Dave Singh Mona Bafadhel Niki Arya Jonathan Marshall Himanshu Parikh Dobrawa Kisielewicz Charlotta Movitz Karin Bowen Mehul Patel Step up to triple therapy versus switch to dual bronchodilator therapy in patients with COPD on an inhaled corticosteroid/long-acting β2-agonist: post-hoc analyses of KRONOS Respiratory Research Chronic obstructive pulmonary disease Exacerbations Lung function Triple therapy |
| title | Step up to triple therapy versus switch to dual bronchodilator therapy in patients with COPD on an inhaled corticosteroid/long-acting β2-agonist: post-hoc analyses of KRONOS |
| title_full | Step up to triple therapy versus switch to dual bronchodilator therapy in patients with COPD on an inhaled corticosteroid/long-acting β2-agonist: post-hoc analyses of KRONOS |
| title_fullStr | Step up to triple therapy versus switch to dual bronchodilator therapy in patients with COPD on an inhaled corticosteroid/long-acting β2-agonist: post-hoc analyses of KRONOS |
| title_full_unstemmed | Step up to triple therapy versus switch to dual bronchodilator therapy in patients with COPD on an inhaled corticosteroid/long-acting β2-agonist: post-hoc analyses of KRONOS |
| title_short | Step up to triple therapy versus switch to dual bronchodilator therapy in patients with COPD on an inhaled corticosteroid/long-acting β2-agonist: post-hoc analyses of KRONOS |
| title_sort | step up to triple therapy versus switch to dual bronchodilator therapy in patients with copd on an inhaled corticosteroid long acting β2 agonist post hoc analyses of kronos |
| topic | Chronic obstructive pulmonary disease Exacerbations Lung function Triple therapy |
| url | https://doi.org/10.1186/s12931-025-03234-5 |
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