PMID- 35001708
OWN - NLM
STAT- MEDLINE
DCOM- 20220307
LR  - 20220307
IS  - 1753-4666 (Electronic)
IS  - 1753-4658 (Print)
IS  - 1753-4658 (Linking)
VI  - 16
DP  - 2022 Jan-Dec
TI  - Quantitative analysis of efficacy and safety of LABA/LAMA fixed-dose combinations 
      in the treatment of stable COPD.
PG  - 17534666211066068
LID - 10.1177/17534666211066068 [doi]
LID - 17534666211066068
AB  - OBJECTIVE: This study aimed to quantitatively compare the efficacy and safety of 
      long-acting beta2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose 
      combinations (FDCs) for the treatment of stable chronic obstructive pulmonary 
      disease (COPD), especially in terms of their loss of efficacy in lung function. 
      METHODS: Randomized controlled clinical trials of LABA/LAMA FDCs for the 
      treatment of stable COPD were comprehensively searched for in public databases. 
      Pharmacodynamic models were established to describe the time course of the 
      primary outcome [trough forced expiratory volume in the first second (FEV(1))]. 
      Secondary outcomes [COPD exacerbations, St. George's Respiratory Questionnaire 
      (SGRQ), Transition Dyspnoea Index (TDI), and rescue medication use] and safety 
      outcomes [mortality, serious adverse events (SAEs), and withdrawals due to 
      adverse events (AEs)] were also compared via a meta-analysis. RESULTS: A total of 
      22 studies involving 16,486 participants were included in this study. The results 
      showed that in terms of primary outcome (change from baseline in trough FEV(1)), 
      the efficacy of vilanterol/umeclidinium was the highest, while the efficacy of 
      formoterol/aclidinium was the lowest, with a maximum effect value (E(max)) of 
      0.185 L [95% confidence interval (CI): 0.173-0.197 L] and 0.119 L (95% CI: 
      0.103-0.135 L), respectively. The efficacy of other drugs, such as 
      formoterol/glycopyrronium, indacaterol/glycopyrronium, and olodaterol/tiotropium, 
      were comparable, and their E(max) values were 0.150-0.177 L. Except for 
      vilanterol/umeclidinium, the other four LABA/LAMA FDCs showed a certain degree of 
      loss of efficacy. Compared with the efficacy at 2 days, the trough FEV(1) (L) 
      relative to baseline at 24 weeks decreased by 0.029-0.041 L. In terms of 
      secondary outcomes, the efficacy of different LABA/LAMA FDCs was similar in TDI 
      and rescue medication use. However, formoterol/aclidinium was better in 
      preventing the COPD exacerbations, while vilanterol/umeclidinium was the best in 
      terms of SGRQ. In addition, different LABA/LAMA FDCs and placebo had similar 
      safety outcomes. CONCLUSION: The present findings may provide necessary 
      quantitative information for COPD medication guidelines.
FAU - Gong, Yiwen
AU  - Gong Y
AUID- ORCID: 0000-0002-2415-8537
AD  - Center for Drug Clinical Evaluation, Shanghai University of Traditional Chinese 
      Medicine, Shanghai, China.
FAU - Lv, Yinghua
AU  - Lv Y
AD  - Center for Drug Clinical Evaluation, Shanghai University of Traditional Chinese 
      Medicine, Shanghai, China.
FAU - Liu, Hongxia
AU  - Liu H
AD  - Center for Drug Clinical Evaluation, Shanghai University of Traditional Chinese 
      Medicine, Shanghai, China.
FAU - Zheng, Qingshan
AU  - Zheng Q
AD  - Center for Drug Clinical Evaluation, Shanghai University of Traditional Chinese 
      Medicine, No. 1200 Cailun Road, Shanghai 201203, China.
FAU - Li, Lujin
AU  - Li L
AD  - Center for Drug Clinical Evaluation, Shanghai University of Traditional Chinese 
      Medicine, No. 1200 Cailun Road, Shanghai 201203, China.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Ther Adv Respir Dis
JT  - Therapeutic advances in respiratory disease
JID - 101316317
RN  - 0 (Adrenergic beta-2 Receptor Agonists)
RN  - 0 (Bronchodilator Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (Muscarinic Antagonists)
RN  - V92SO9WP2I (Glycopyrrolate)
RN  - W34SHF8J2K (Formoterol Fumarate)
SB  - IM
MH  - Adrenergic beta-2 Receptor Agonists
MH  - Bronchodilator Agents
MH  - Drug Combinations
MH  - Forced Expiratory Volume
MH  - Formoterol Fumarate
MH  - Glycopyrrolate
MH  - Humans
MH  - *Muscarinic Antagonists
MH  - *Pulmonary Disease, Chronic Obstructive/diagnosis/drug therapy
MH  - Treatment Outcome
PMC - PMC8743917
OTO - NOTNLM
OT  - LABA/LAMA fixed-dose combinations
OT  - chronic obstructive pulmonary disease
OT  - model-based meta-analysis
OT  - trough forced expiratory volume in 1 second
COIS- Conflict of interest statement: The authors declared no potential conflicts of 
      interest with respect to the research, authorship, and/or publication of this 
      article.
EDAT- 2022/01/11 06:00
MHDA- 2022/03/08 06:00
PMCR- 2022/01/08
CRDT- 2022/01/10 08:48
PHST- 2022/01/10 08:48 [entrez]
PHST- 2022/01/11 06:00 [pubmed]
PHST- 2022/03/08 06:00 [medline]
PHST- 2022/01/08 00:00 [pmc-release]
AID - 10.1177_17534666211066068 [pii]
AID - 10.1177/17534666211066068 [doi]
PST - ppublish
SO  - Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666211066068. doi: 
      10.1177/17534666211066068.