FULFIL evaluated once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus twicedaily budesonide/formoterol (BUD/FOR) inhaled corticosteroid/long-acting b2-agonist (ICS/LABA) dual therapy in patients with symptomatic chronic obstructive pulmonary disease (COPD) who were at risk of exacerbations. FULFIL showed clinically meaningful and statistically significant improvements in lung function and health-related quality of life, as well as reductions in moderate/severe exacerbation annualized rates in patients receiving FF/UMEC/VI versus those receiving BUD/FOR. Severe exacerbations place a high clinical and financial burden on both patients and healthcare systems. This post hoc analysis examined treatment effects on severe exacerbation rates in the FULFIL study.
Previous evidence suggests significant improvement in treatment adherence in COPD patients who utilize fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) compared with multiple-inhaler triple therapy (MITT). There is a lack of realworld evidence on whether improved adherence translates to improved patient outcomes. This study examined the impact of switching from MITT to FF/UMEC/VI on moderate and severe COPD exacerbations in a real-world setting.
PURPOSE: FULFIL enrolled patients with symptomatic chronic obstructive pulmonary disease (COPD) at risk of exacerbations. FULFIL demonstrated a clinically meaningful and statistically significant reduction in the annualized rate of moderate/severe exacerbations in patients treated with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus budesonide/formoterol (BUD/FOR). Prior history of exacerbations is one of the major risk factors for future exacerbations. The FULFIL study included patients with no prior exacerbations in the past year; therefore, it is of interest to investigate the effect of triple versus dual therapy on exacerbation outcomes in these patients. This post hoc analysis investigated exacerbation outcomes in FULFIL in patients with no exacerbations in the year prior to study entry.METHODS: FULFIL was a Phase 3, 24-week, randomized, double-blind, double-dummy trial in 1810 patients $40 years of age with symptomatic COPD (COPD Assessment Test score $10) at risk of exacerbations who were randomized to once-daily FF/ UMEC/VI 100/62.5/25mg (ELLIPTA inhaler; N¼911) or twice-daily BUD/FOR 400/12mg (Turbuhaler inhaler; N¼899). Patients were required to have a forced expiratory volume in 1 s (FEV1) <50% predicted and no exacerbations in the past year or FEV1 $50-<80% predicted and $2 moderate or $1 severe exacerbation in the past year. On-treatment annualized rates of moderate/ severe and severe exacerbations at Week 24 were evaluated by treatment group for patients with no exacerbations in the year prior to study entry using a generalized linear model assuming a negative binomial distribution. Moderate exacerbations were those requiring corticosteroid or antibiotic therapy; severe exacerbations were those resulting in hospitalization.
RESULTS:Of the 1810 patients in the intent-to-treat population, 630(35%) had no prior exacerbations (FF/UMEC/VI, n¼313; BUD/FOR, n¼317). Of these patients, 37 (12%) and 51 (16%) experienced on-treatment moderate/severe exacerbations with FF/ UMEC/VI and BUD/FOR over 24 weeks, respectively; numbers for severe exacerbations were 5 (2%) and 8 (3%), respectively. Patients receiving FF/UMEC/VI vs BUD/FOR had numerically lower annualized rates of moderate/severe exacerbations (mean annualized rate: 0.29 vs 0.43; rate ratio: 0.67 [95% confidence interval [CI]: 0.43, 1.04]; p¼0.073) and severe exacerbations (mean annualized rates: 0.013 vs 0.020, respectively; rate ratio: 0.62 [95% CI: 0.18, 2.13]; p¼0.446).CONCLUSIONS: These results suggest FF/UMEC/VI may reduce moderate/severe exacerbation rates compared with BUD/FOR in patients with symptomatic COPD who had no exacerbations in the prior year.CLINICAL IMPLICATIONS: These results suggest that there may be exacerbation benefits associated with once-daily singleinhaler FF/UMEC/VI triple therapy in COPD patients with severe airflow limitation and no history of exacerbations.Funding: GSK (CTT116853/NCT02345161).
Several studies have shown increased risk of adverse events (AEs) with chronic use of oral corticosteroids (OCS) in patients with asthma, but patterns of OCS use, including chronic overuse and potential OCS-related AEs, have not been well characterized in the COPD population. This study assessed the burden of OCS overuse in a cohort of real-world COPD patients identified in the MarketScan Commercial and Medicare Supplemental Databases.
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