TY - JOUR
T1 - Triple versus LAMA/LABA combination therapy for patients with COPD
T2 - a systematic review and meta-analysis
AU - Koarai, Akira
AU - Yamada, Mitsuhiro
AU - Ichikawa, Tomohiro
AU - Fujino, Naoya
AU - Kawayama, Tomotaka
AU - Sugiura, Hisatoshi
N1 - Funding Information:
We appreciated the staffs of the Japan Council for Quality Health Care for supporting the systematic review and meta-analysis. We also thank Mr. Brent Bell for reading this manuscript.
Funding Information:
AK reports grants from Novartis, personal fees for lectures from Astellas, AstraZeneca, Kyorin, Novartis, Sanofi and Taiho, and personal fees for lectures and consulting from Boehringer Ingelheim and GlaxoSmithKline, outside the submitted work. MY reports grants from Japan Society for the Promotion of Science and Novartis, and personal fees for lectures from AstraZeneca, Meiji Seika Pharma, Novartis, Daiichi Sankyo, Sanofi and Boehringer Ingelheim, outside the submitted work. TI has nothing to disclose. NF reports personal fees for lectures from AstraZeneca, outside the submitted work. TK reports grants from Novartis, and personal fees for lectures from AstraZeneca, Boehringer Ingelheim, Meiji Seika Pharma and GlaxoSmithKline, outside the submitted work. HS reports grants from MSD and Novartis, personal fees for lectures from Astellas, Kyorin, Novartis and Sanofi, and personal fees for lectures and consulting from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline, outside the submitted work.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Chronic obstructive pulmonary disease
KW - Exacerbations
KW - Inhaled corticosteroid
KW - Mortality
KW - Pneumonia
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U2 - 10.1186/s12931-021-01777-x
DO - 10.1186/s12931-021-01777-x
M3 - Article
C2 - 34154582
AN - SCOPUS:85108989704
SN - 1465-9921
VL - 22
JO - Respiratory Research
JF - Respiratory Research
IS - 1
M1 - 183
ER -