Which Drug Combination Works Best to Reduce Acute COPD Exacerbations?
A higher blood eosinophil count was associated with a greater protective effect of ICS/LABA/LAMA against severe acute COPD exacerbations.
A combination of inhaled corticosteroids (ICS)/long-acting β2-agonist (LABA)/long-acting muscarinic receptor antagonist (LAMA) is possibly more effective than a LABA/LAMA combination or single long-acting bronchodilator therapy in reducing the risk for moderate or severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD), according to a meta-analysis published in the European Respiratory Journal.
A total of 14 randomized clinical trials consisting of 16,751 patients with COPD were included in the meta-analysis. Patients were treated with either an ICS/LABA/LAMA combination (57.3%), LABA/LAMA combination (28.4%), or single long-acting bronchodilator therapy (14.3%).
Researchers examined the pooled impact of the ICS/LABA/LAMA combination vs the LABA/LAMA combination and single long-acting bronchodilator therapy on the moderate or severe AECOPD risk as well as the change in trough forced expiratory volume in 1 second from baseline and pneumonia risk. Secondary end points of the analysis included the effect of the ICS/LABA/LAMA combination vs the LABA/LAMA combination and single long-acting bronchodilator therapy on the change in St. George's Respiratory Questionnaire baseline score as well as the risk for serious adverse events.
Compared with combination treatment with LABA/LAMA, the ICS/LABA/LAMA combination therapy was associated with a significantly greater pooled risk reduction in disease exacerbation (relative risk [RR], 0.70; 95% CI, 0.53-0.94; P <.001). Protection against disease exacerbation was greater in patients with blood eosinophil counts of ≥300 cells/μL (RR, 0.57; 95% CI, 0.48-0.68). In addition, ICS/LABA/LAMA improved trough forced expiratory volume in 1 second significantly more than LABA/LAMA (mean difference, mL: +37.94, 95%CI 18.83-53.89; P <.001).
The triple ICS/LABA/LAMA combination was also more effective than the LABA/LAMA combination (RR, 0.78; 95% CI, 0.69-0.89) or single long-acting bronchodilator therapy (RR, 0.59; 95% CI, 0.42-0.82) (P <.001) for the end point of severe AECOPD. A higher blood eosinophil count was associated with a greater protective effect of ICS/LABA/LAMA against severe AECOPD and was found to be a modifier of the triple combination strategy in preventing moderate or severe AECOPD risk (coefficient –0.001; P <.05).
“Nevertheless, we must emphasize that while meta-analyses have evolved as a technique useful for summarizing a large number of [randomized clinical trials] and for resolving discrepancies raised by these trials, they deal with populations, not with single individuals,” the investigators wrote when explaining the limitations of their findings. “Thus, clinicians must use clinical judgment when applying the conclusions of this and other studies to the individual patient.”
Cazzola M, Rogliani P, Calzetta L, Matera MG. Triple therapy versus single and dual long-acting bronchodilator therapy in chronic obstructive pulmonary disease: a systematic review and meta-analysis [published online October 11, 2018]. Eur Respir J. doi:10.1183/13993003.01586-2018