<p>Efficacy and Safety of LAMA/LABA Fixed-Dose Combination Therapies in Chronic Obstructive Pulmonary Disease: A Systematic Review of Direct and Indirect Treatment Comparisons</p>

Abstract

Background: This literature review assessed comparative efficacy and safety of long-acting muscarinic antagonist/long-acting β 2-agonist (LAMA/LABA) fixed-dose combinations (FDCs) in patients with COPD and moderate-to-very severe airflow limitation, using evidence from direct (head-to-head) and indirect treatment comparisons. Methods: Two systematic literature reviews were conducted to identify direct comparisons (head-to-head randomized controlled trials [RCTs]) and indirect comparisons (network metaanalyses [NMAs]; indirect treatment comparisons; meta-analyses) in patients with COPD with moderate-to-very severe airflow limitation. Study/Analysis characteristics, eligibility criteria, patient characteristics, and overall conclusions were extracted from relevant publications. The review of indirect comparisons focused on NMAs reporting efficacy outcomes at 12 and 24 weeks of treatment (established durations of symptomatic studies in COPD recommended by regulators). Results: Direct comparisons: Four RCTs that provided head-to-head comparisons of LAMA/ LABA FDCs were identified, and these varied in their study design, included patient population and reported endpoints. While some differences in lung function outcomes were noted, where assessed, LAMA/LABA FDCs had comparable efficacy in improving symptoms, health status, exacerbations, and comparable safety profiles. However, the differences in study methodology and patient characteristics between these studies made it difficult to draw generalizable conclusions regarding the comparative effectiveness of LAMA/LABA FDCs from the direct comparisons alone. Indirect comparisons: Six NMAs were identified that reported indirect comparisons between LAMA/ LABA FDCs; five of these were within the pre-defined scope of this review. Although the scope of each NMA varied, all five concluded that LAMA/LABA FDCs were generally comparable in terms of lung function improvements, patient-reported outcomes, and safety (where assessed). Conclusion: Although there were some inconsistencies between the outcomes of RCTs and NMAs for lung function, the totality of lung function, symptoms, exacerbations, and safety data suggests that currently available LAMA/LABA FDCs have comparable efficacy and safety in patients with COPD and moderate-to-very severe airflow limitation.

Comparative efficacy and safety of glycopyrronium/formoterol fixed-dose combination versus glycopyrronium monotherapy in patients with moderate-to–severe COPD

“…The change from baseline in FEV 1 in the GB/FF group was in line with the previous combination of LAMA and LABA either as FDC or separately administered via pMDI or DPI. [ 20 22 ] In a meta-analysis of 1868 patients from randomized trials of ≥2 weeks duration, LAMA/LABA combination (TIO/FORMO) significantly improved average FEV 1 compared to tiotropium only. [ 23 ] In another large meta-analysis of 34,617 patients from randomized controlled trial studies of ≥10 weeks, all licensed FDC of LAMA/LABA showed significant improvement in lung function in terms of trough, peak, and AUC 0–24h FEV 1 compared to placebo.…”

Stepwise management of COPD: What is next after bronchodilation?

“…Although some studies have suggested that different LABA/LAMA fixed-dose combinations have specific efficacy profiles in COPD that might allow more personalized therapy, 18 systematic reviews evaluating intra-class efficacy for LABA/ LAMA and LABA/LAMA/ICS have not shown any clear evidence of greater efficacy associated with specific combinations. [19][20][21][22][23] A summary of international and national treatment guidelines for COPD is presented in Table 1.…”

How can the findings of the EMAX trial on long-acting bronchodilation in chronic obstructive pulmonary disease be applied in the primary care setting?

“…Systematic meta-analyses have concluded that LAMA/LABA dual therapy is superior to LAMA and LABA monotherapies. 5 , 30 In addition, several head-to-head trials 31 , 32 and systematic meta-analyses 33 , 34 suggest that once-daily UMEC/VI is non-inferior or superior to other available LAMA/LABAs.…”