Background: Dual bronchodilation with a long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) fixed-dose combination (FDC) is an established treatment strategy for chronic obstructive pulmonary disease (COPD). The relative efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI 18/9.6 μg) in patients with moderate-to-very severe COPD, compared with other licensed LAMA/LABA FDCs, was investigated using an integrated Bayesian network meta-analysis (NMA). Methods: A systematic literature review and subsequent screening process identified randomized controlled trials of ⩾10 weeks’ duration that enrolled patients aged ⩾40 years with moderate-to-very severe COPD and included at least one LAMA/LABA FDC or open LAMA + LABA treatment arm. NMAs were conducted for outcomes including change from baseline in forced expiratory volume in 1 s (FEV1), St George’s Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI) parameters, annualized rate of exacerbations, use of rescue medication, adverse events, and all-cause withdrawals. Meta-regression and sensitivity analyses accounted for heterogeneity across studies. Results: In total, 29 studies including 34,617 patients contributed to the NMA for efficacy or safety outcomes at week 24 or exacerbations. For all LAMA/LABA FDCs with data available, significantly greater improvements in FEV1 [trough, peak, and area under the curve (AUC)0–4], SGRQ total score and TDI focal score at week 24, and annualized rate of moderate-to-severe exacerbations, were observed versus placebo. Where indirect comparisons were possible, differences between GFF MDI and other LAMA/LABA FDCs were small relative to established margins of clinical relevance, and not statistically significant. The safety and tolerability profile of GFF MDI was consistent with other LAMA/LABA FDCs and placebo. The results of the meta-regression were generally similar to the base case. Conclusions: GFF MDI demonstrated comparable efficacy and safety outcomes to other LAMA/LABA FDCs. Personalization of treatment choice within the class on the basis of other factors such as patient preference may be appropriate.

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Articles were also identified by hand searching for references cited within screened publications. Findings reported in the selected studies were synthesized qualitatively. 10 Additional articles were identified during the writing of the report and manuscript after the formal targeted literature

Introduction: This retrospective, observational cohort study utilized an integrated dataset from an electronic health records system and a claims database to describe demographic and clinical characteristics, healthcare resource utilization (HCRU), and treatment patterns in COPD patients initiating long-acting muscarinic antagonist (LAMA)/long-acting β 2 -agonist (LABA) fixed-dose combination (FDC) treatment in the USA. Methods: Patients were aged ≥40 years and had a COPD diagnosis (Practice Fusion system) and ≥1 prescription of LAMA/LABA FDC therapy, with an index date (first prescription) 1 May 2014-31 December 2017. For the HCRU analysis, patients had ≥2 claims from the Symphony Health database within 12 months before index. All analyses of outcomes relating to demographic and clinical characteristics, HCRU, and treatment patterns were descriptive. Results: Patients initiating LAMA/LABA FDCs (n=8224) had a mean age of 67.9 years, 52.8% were female, and mean BMI was 29.2 kg/m 2 . The most common comorbidities were cardiovascular disease (74.3%), hypertension (64.0%), and hyperlipidemia (45.6%). In the 12 months prior to index, 53.1% of patients had used inhaled therapy: 23.4% short-acting therapy only, 16.7% short-acting and maintenance therapy, and 13.1% maintenance therapy only. Amongst users of inhaled therapies, the pMDI was the most frequently used device (64.3%, n=2812/4370). Of 7050 patients included in the HCRU analysis, 79.8% had COPDrelated costs; mean cost/patient was $4174. Mean COPD-related costs per patient for moderate and severe exacerbations were $910 and $23,208, respectively. Per-patient costs included $23,032 for inpatient visits, $2358 for emergency visits, $4432 for outpatient visits, and $1989 for pharmacy claims. Conclusion: This observational study is the first to describe the real-world demographic and clinical characteristics and HCRU of patients initiating LAMA/LABA FDC treatment in the USA. Patients were generally elderly and overweight, with comorbidities of CVD, hypertension, and hyperlipidemia. Inpatient visits were the largest contributor to COPD-related costs per patient in the year prior to initiation of LAMA/LABA FDCs.

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.