Introduction: Comparative data on the efficacies of long-acting muscarinic antagonist (LAMA) and long-acting b 2 -agonist (LABA) combinations for the treatment of moderate-to-very-severe chronic obstructive pulmonary disease (COPD) are limited. The aim of this Bayesian network meta-analysis (NMA) is to assess the relative efficacies of available open

BackgroundAclidinium bromide is a new long-acting muscarinic antagonist (LAMA) indicated for maintenance bronchodilator treatment of chronic obstructive pulmonary disease (COPD). The efficacy of aclidinium was compared with tiotropium and glycopyrronium, using a network meta-analysis (NMA) of randomized controlled trials (RCTs) in moderate-to-severe COPD patients.MethodsA systematic review was performed to identify RCTs evaluating aclidinium 400 μg twice daily (BID), glycopyrronium 50 μg once daily (OD), tiotropium 18 μg OD, or tiotropium 5 μg OD in adults with moderate-to-severe COPD. The outcomes of interest were: trough forced expiratory volume in 1 second (FEV1); St George’s Respiratory Questionnaire (SGRQ) total score and proportion of patients achieving ≥4 unit change; Transition Dyspnea Index (TDI) focal score and proportion of patients achieving ≥1 point change. The results were synthesized by means of a Bayesian NMA.ResultsTwenty-one studies (22,542 patients) were included: aclidinium 400 μg BID (three studies); tiotropium 5 μg OD (three studies); tiotropium 18 μg OD (13 studies); and glycopyrronium 50 μg OD (two studies). Regarding trough FEV1 at 24 weeks, aclidinium demonstrated comparable efficacy to tiotropium 5 μg (difference in change from baseline [CFB]), (0.02 L [95% credible interval CrI −0.05, 0.09]); tiotropium 18 μg (0.02 L [95% CrI −0.05, 0.08]); and glycopyrronium (0.00 L [95% CrI −0.07, 0.07]). Aclidinium resulted in higher improvement in SGRQ score at 24 weeks, compared to tiotropium 5 μg (difference in CFB, −2.44 [95% CrI −4.82, −0.05]); and comparable results to tiotropium 18 μg (−1.80 [95% CrI −4.52, 0.14]) and glycopyrronium (−1.52 [95% CrI −4.08, 1.03]). Improvements in TDI score were comparable for all treatments.ConclusionMaintenance treatment with aclidinium 400 μg BID is expected to produce similar improvements in lung function, health-related quality of life, and dyspnea compared to tiotropium 5 μg OD; tiotropium 18 μg OD; and glycopyrronium 50 μg OD.

BackgroundRandomized, controlled trials comparing long-acting muscarinic antagonist (LAMA) efficacy in COPD are limited. This network meta-analysis (NMA) assessed the relative efficacy of tiotropium 18 µg once-daily (OD) and newer agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium 62.5 µg OD).MethodsA systematic literature review identified randomized, controlled trials of adult COPD patients receiving LAMAs. A NMA within a Bayesian framework examined change from baseline in trough forced expiratory volume in 1 second (FEV1), transitional dyspnea index focal score, St George’s Respiratory Questionnaire score, and rescue medication use.ResultsTwenty-four studies (n=21,311) compared LAMAs with placebo/each other. Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively, demonstrated favorable results versus placebo, for change from baseline (95% credible interval) in 12-week trough FEV1 (primary endpoint: 101.40 mL [77.06–125.60]; 117.20 mL [104.50–129.90]; 114.10 mL [103.10–125.20]; 136.70 mL [104.20–169.20]); 24-week trough FEV1 (128.10 mL [84.10–172.00]; 135.80 mL [123.10–148.30]; 106.40 mL [95.45–117.30]; 115.00 mL [74.51–155.30]); 24-week St George’s Respiratory Questionnaire score (−4.60 [−6.76 to −2.54]; −3.14 [−3.83 to −2.45]; −2.43 [−2.92 to −1.93]; −4.69 [−7.05 to −2.31]); 24-week transitional dyspnea index score (1.00 [0.41–1.59]; 1.01 [0.79–1.22]; 0.82 [0.62–1.02]; 1.00 [0.49–1.51]); and 24-week rescue medication use (data not available; −0.41 puffs/day [−0.62 to −0.20]; −0.52 puffs/day [−0.74 to −0.30]; −0.30 puffs/day [−0.81 to 0.21]). For 12-week trough FEV1, differences in change from baseline (95% credible interval) were −12.8 mL (−39.39 to 13.93), aclidinium versus tiotropium; 3.08 mL (−7.58 to 13.69), glycopyrronium versus tiotropium; 22.58 mL (−11.58 to 56.97), umeclidinium versus tiotropium; 15.90 mL (−11.60 to 43.15), glycopyrronium versus aclidinium; 35.40 mL (−5.06 to 76.07), umeclidinium versus aclidinium; and 19.50 mL (−15.30 to 54.38), umeclidinium versus glycopyrronium. Limitations included inhaler-related factors and safety; longer-term outcomes were not considered.ConclusionThe new LAMAs studied had at least comparable efficacy to tiotropium, the established class standard. Choice should depend on physician’s and patient’s preference.

ObjectiveMultiple sclerosis (MS) is a chronic, neurodegenerative autoimmune disorder affecting the central nervous system. Relapsing–remitting MS (RRMS) is the most common clinical form of MS and affects ∼85% of cases at onset. Highly active (HA) and rapidly evolving severe (RES) RRMS are 2 forms of RRMS amenable to disease-modifying therapies (DMT). This study explored the efficacy of fingolimod relative to other DMTs for the treatment of HA and RES RRMS.MethodsA systematic literature review (SLR) was conducted to identify published randomised controlled trials in HA and RES RRMS. Identified evidence was vetted, and a Bayesian network meta-analysis (NMA) was performed to evaluate the relative efficacy of fingolimod versus dimethyl fumarate (DMF) in HA RRMS and versus natalizumab in RES RRMS.ResultsFor HA RRMS, the SLR identified 2 studies with relevant patient subgroup data: 1 comparing fingolimod with placebo and the other comparing DMF with placebo. 3 studies were found for RES RRMS: 1 comparing fingolimod with placebo and 2 studies comparing natalizumab with placebo. NMA results in the HA population showed a favourable numerical trend of fingolimod versus DMF assessed for annualised relapse rate (ARR) and 3-month confirmed disability progression. For the RES population, the results identified an increase of ARR and 3-month confirmed disability progression for fingolimod versus natalizumab (not statistically significant). Sparse study data and the consequently high uncertainty around the estimates restricted our ability to demonstrate statistical significance in the studied subgroups.ConclusionsData limitations are apparent when conducting an informative indirect comparison for the HA and RES RRMS subgroups as the subgroups analyses were retrospective analyses of studies powered to indicate differences across entire study populations. Comparisons across treatments in HA or RES RRMS will be associated with high levels of uncertainty until new data are collected for these subgroups.

ObjectiveChoosing therapies for type 2 diabetes that are both effective and cost-effective is vital as healthcare systems worldwide aim to maximize health of the population. The present analysis assessed the cost-effectiveness of once-weekly semaglutide (a novel glucagon-like peptide-1 (GLP-1) receptor agonist) versus insulin glargine U100 (the most commonly used basal insulin) and versus dulaglutide (an alternative once-weekly GLP-1 receptor agonist), from a societal perspective in the Netherlands.Research design and methodsThe IQVIA CORE Diabetes Model was used to project outcomes for once-weekly semaglutide 0.5 mg and 1 mg versus insulin glargine U100, once-weekly semaglutide 0.5 mg versus dulaglutide 0.75 mg, and once-weekly semaglutide 1 mg versus dulaglutide 1.5 mg. Clinical data were taken from the SUSTAIN 4 and SUSTAIN 7 clinical trials. The analysis captured direct and indirect costs, mortality, and the impact of diabetes-related complications on quality of life.ResultsProjections of outcomes suggested that once-weekly semaglutide 0.5 mg was associated with improved quality-adjusted life expectancy by 0.19 quality-adjusted life years (QALYs) versus insulin glargine U100 and 0.07 QALYs versus dulaglutide 0.75 mg. Once-weekly semaglutide 1 mg was associated with mean increases in quality-adjusted life expectancy of 0.27 QALYs versus insulin glargine U100 and 0.13 QALYs versus dulaglutide 1.5 mg. Improvements came at an increased cost versus insulin glargine U100, with incremental cost-effectiveness ratios from a societal perspective of €4988 and €495 per QALY gained for once-weekly semaglutide 0.5 mg and 1 mg, respectively, falling below Netherlands-specific willingness-to-pay thresholds. Improvements versus dulaglutide came at a reduced cost from a societal perspective for both doses of once-weekly semaglutide.ConclusionsOnce-weekly semaglutide is cost-effective versus insulin glargine U100, and dominant versus dulaglutide 0.75 and 1.5 mg for the treatment of type 2 diabetes, and represents a good use of healthcare resources in the Netherlands.