Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis
Abstract Background Recently, the addition of inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy has been recommended for patients with COPD who have severe symptoms and a history of exacerbations because it reduces the ex...
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doaj-6f9ca0cc973c410a949bf693cfbc95722021-06-27T11:16:41ZengBMCRespiratory Research1465-993X2021-06-0122111110.1186/s12931-021-01777-xTriple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysisAkira Koarai0Mitsuhiro Yamada1Tomohiro Ichikawa2Naoya Fujino3Tomotaka Kawayama4Hisatoshi Sugiura5Department of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDivision of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineAbstract Background Recently, the addition of inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy has been recommended for patients with COPD who have severe symptoms and a history of exacerbations because it reduces the exacerbations. In addition, a reducing effect on mortality has been shown by this treatment. However, the evidence is mainly based on one large randomized controlled trial IMPACT study, and it remains unclear whether the ICS add-on treatment is beneficial or not. Recently, a large new ETHOS trial has been performed to clarify the ICS add-on effects. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety including ETHOS trial. Methods We searched relevant randomized control trials (RCTs) and analyzed the exacerbations, quality of life (QOL), dyspnea symptom, lung function and adverse events including pneumonia and mortality, as the outcomes of interest. Results We identified a total of 6 RCTs in ICS add-on protocol (N = 13,579). ICS/LAMA/LABA treatment (triple therapy) significantly decreased the incidence of exacerbations (rate ratio 0.73, 95% CI 0.64–0.83) and improved the QOL score and trough FEV1 compared to LAMA/LABA. In addition, triple therapy significantly improved the dyspnea score (mean difference 0.33, 95% CI 0.18–0.48) and mortality (odds ratio 0.66, 95% CI 0.50–0.87). However, triple therapy showed a significantly higher incidence of pneumonia (odds ratio 1.52, 95% CI 1.16–2.00). In the ICS-withdrawal protocol including 2 RCTs, triple therapy also showed a significantly better QOL score and higher trough FEV1 than LAMA/LABA. Concerning the trough FEV1, QOL score and dyspnea score in both protocols, the differences were less than the minimal clinically important difference. Conclusion Triple therapy causes a higher incidence of pneumonia but is a more preferable treatment than LAMA/LABA due to the lower incidence of exacerbations, higher trough FEV1 and better QOL score. In addition, triple therapy is also superior to LABA/LAMA due to the lower mortality and better dyspnea score. However, these results should be only applied to patients with symptomatic moderate to severe COPD and a history of exacerbations. Clinical Trial Registration: PROSPERO; CRD42020191978.https://doi.org/10.1186/s12931-021-01777-xChronic obstructive pulmonary diseaseExacerbationsInhaled corticosteroidMortalityPneumonia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Akira Koarai Mitsuhiro Yamada Tomohiro Ichikawa Naoya Fujino Tomotaka Kawayama Hisatoshi Sugiura |
spellingShingle |
Akira Koarai Mitsuhiro Yamada Tomohiro Ichikawa Naoya Fujino Tomotaka Kawayama Hisatoshi Sugiura Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis Respiratory Research Chronic obstructive pulmonary disease Exacerbations Inhaled corticosteroid Mortality Pneumonia |
author_facet |
Akira Koarai Mitsuhiro Yamada Tomohiro Ichikawa Naoya Fujino Tomotaka Kawayama Hisatoshi Sugiura |
author_sort |
Akira Koarai |
title |
Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis |
title_short |
Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis |
title_full |
Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis |
title_fullStr |
Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis |
title_full_unstemmed |
Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis |
title_sort |
triple versus lama/laba combination therapy for patients with copd: a systematic review and meta-analysis |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-993X |
publishDate |
2021-06-01 |
description |
Abstract Background Recently, the addition of inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy has been recommended for patients with COPD who have severe symptoms and a history of exacerbations because it reduces the exacerbations. In addition, a reducing effect on mortality has been shown by this treatment. However, the evidence is mainly based on one large randomized controlled trial IMPACT study, and it remains unclear whether the ICS add-on treatment is beneficial or not. Recently, a large new ETHOS trial has been performed to clarify the ICS add-on effects. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety including ETHOS trial. Methods We searched relevant randomized control trials (RCTs) and analyzed the exacerbations, quality of life (QOL), dyspnea symptom, lung function and adverse events including pneumonia and mortality, as the outcomes of interest. Results We identified a total of 6 RCTs in ICS add-on protocol (N = 13,579). ICS/LAMA/LABA treatment (triple therapy) significantly decreased the incidence of exacerbations (rate ratio 0.73, 95% CI 0.64–0.83) and improved the QOL score and trough FEV1 compared to LAMA/LABA. In addition, triple therapy significantly improved the dyspnea score (mean difference 0.33, 95% CI 0.18–0.48) and mortality (odds ratio 0.66, 95% CI 0.50–0.87). However, triple therapy showed a significantly higher incidence of pneumonia (odds ratio 1.52, 95% CI 1.16–2.00). In the ICS-withdrawal protocol including 2 RCTs, triple therapy also showed a significantly better QOL score and higher trough FEV1 than LAMA/LABA. Concerning the trough FEV1, QOL score and dyspnea score in both protocols, the differences were less than the minimal clinically important difference. Conclusion Triple therapy causes a higher incidence of pneumonia but is a more preferable treatment than LAMA/LABA due to the lower incidence of exacerbations, higher trough FEV1 and better QOL score. In addition, triple therapy is also superior to LABA/LAMA due to the lower mortality and better dyspnea score. However, these results should be only applied to patients with symptomatic moderate to severe COPD and a history of exacerbations. Clinical Trial Registration: PROSPERO; CRD42020191978. |
topic |
Chronic obstructive pulmonary disease Exacerbations Inhaled corticosteroid Mortality Pneumonia |
url |
https://doi.org/10.1186/s12931-021-01777-x |
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