LABA/LAMA more effective than LAMA, LABA/ICS for COPD
Fixed-dose combinations of long-acting β2-agonist (LABA) and muscarinic antagonist (LAMA) offered superior efficacy and comparable safety to LAMA or LABA/inhaled corticosteroid (ICS), the two most commonly prescribed first-line treatments for stable moderate-to-very-severe chronic obstructive pulmonary disease (COPD), according to a meta-analysis.
“The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations vs LAMA or LABA/ICS support their potential role as first-line treatment options in COPD,” said the researchers.
Researchers pooled data from 18 studies (n=20,185) comprising trials comparing 12-week LABA/LAMA treatment with LAMA alone and/or LABA/ICS (using approved doses only) in patients with stable moderate-to-very severe COPD. [Int J Chron Obstruct Pulmon Dis 2017;12:907-922]
At week 12, LABA/LAMA-treated patients had significantly improved trough forced expiratory volume in 1 second vs LAMA alone and LABA/ICS (mean overall difference, 0.07, 95 percent confidence interval [CI], 0.05–0.09; p<0.0001 and mean overall difference, 0.08, 95 percent CI, 0.07–0.09; p<0.0001, respectively).
LABA/LAMA-treated patients also had significantly improved transitional dyspnoea index score (mean difference, 0.5, 95 percent CI, 0.32–0.68; p<0.0001) and St George’s Respiratory Questionnaire score (mean difference, -1.84, 95 percent CI, -2.31 to -1.37, p<0.0001) vs LAMA alone at week 12.
In terms of safety outcomes, lower adverse event (AE) rates were observed with LABA/LAMA vs LABA/ICS (risk ratio [RR], 0.94, 95 percent CI, 0.89–0.99; p=0.02), with significantly fewer incidences of pneumonia in the LABA/LAMA group (RR, 0.59, 95 percent CI, 0.43–0.81; p=0.001).
The researchers underlined the significance of pneumonia-related AEs due to the increased pneumonia risk associated with ICS alone or in combination with LABA, particularly with the ICS fluticasone. [Global Initiative for Chronic Obstructive Lung Disease, www.goldcopd.org, accessed May 18, 2017; Pulm Pharmacol Ther 2016;42:1-6; Lancet Respir Med 2013;1:210-223]
As salmeterol/fluticasone propionate was the only LABA/ICS comparator used in the analysis, and given the lack of direct comparison between LABA/LAMA and LABA alone, definitive conclusions on the relative efficacy of various treatments within the LABA/LAMA class cannot be made, hence the need for further evaluation of drug differences, said the researchers.
“LABAs improve symptoms and [health-related quality of life] more effectively than LAMAs, while LAMAs are superior to LABAs in reducing exacerbations,” said the researchers. Therefore, combining LABAs and LAMAs led to improved results that signified the advantage of dual bronchodilation over LAMA monotherapy or LABA/ICS combinations, they added.
“Including all available LABA/LAMA combinations … allowed us to provide indirect insights on the potential relative efficacy of these drugs … [W]e believe that our analysis provides clinically relevant, high-quality evidence that is applicable to daily clinical practice,” they said.