International Journal of COPD (Sep 2022)
Effect of Recent Exacerbation History on the Efficacy of Once-Daily Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease in the FULFIL Trial
Abstract
Reynold A Panettieri Jr,1 Carlos A Camargo Jr,2 Tariq Cheema,3 Sherif G El Bayadi,4 Stanley Fiel,5 Tania M Vila,6 Renu G Jain,6 Dawn Midwinter,7 Byron Thomashow,8 Andrea Ludwig-Sengpiel,9 David A Lipson10,11 1Child Health Institute of New Jersey, Rutgers University School of Medicine, New Brunswick, NJ, USA; 2Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 3Breathing Disorder Center, Allegheny Health Network, Pittsburgh, PA, USA; 4Department of Medicine, St. Joseph’s Health/SUNY Upstate, Syracuse, NY, USA; 5Atlantic Health Systems/Morristown Medical Center, Morristown, NJ, 07960, USA; 6GSK, Research Triangle Park, NC, USA; 7GSK, Brentford, UK; 8Department of Medicine, Columbia University Medical Center, New York, NY, USA; 9KLB Gesundheitsforschung Lübeck GmbH, Lübeck, Germany; 10Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 11GSK, Collegeville, PA, USACorrespondence: Reynold A Panettieri Jr, Rutgers University School of Medicine, 89 French Street, Suite 4210, New Brunswick, NJ, 08901, USA, Tel +1 732-235-6404, Email [email protected]: In the FULFIL trial, once-daily single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) resulted in reduced moderate/severe exacerbation rates and conferred significant improvements in lung function and health status in patients with chronic obstructive pulmonary disease (COPD) versus twice-daily budesonide/formoterol (BUD/FOR) dual therapy.Methods: FULFIL was a Phase III, randomized, double-blind, double-dummy, parallel-group study. Patients ≥ 40 years of age with symptomatic COPD were randomized 1:1 to FF/UMEC/VI 100/62.5/25 mcg or BUD/FOR 400/12 mcg. In this post hoc analysis, patients were categorized by exacerbation history in the year prior to study entry (≥ 1 moderate/severe exacerbation [recent exacerbation] versus no recent exacerbation). Endpoints included annual rate of on-treatment moderate/severe exacerbations up to Week 24, annual rate of on-treatment severe exacerbations up to Week 24, change from baseline in trough forced expiratory volume in 1 second at Week 24, and change from baseline in health status as measured by St George’s respiratory questionnaire total score at Week 24.Results: Of the 1810 patients in the intent-to-treat population, 1180 (65%) had one or more moderate/severe exacerbation in the year prior to entry, while 630 (35%) patients did not. FF/UMEC/VI versus BUD/FOR significantly reduced moderate/severe exacerbation rates in the recent exacerbation subgroup (mean annualized rate: 0.19 vs 0.29; rate ratio [95% confidence interval [CI]]: 0.64: [0.45, 0.91]; p=0.014) and numerically reduced moderate/severe exacerbation rates in the no recent exacerbation subgroup (mean annualized rate: 0.29 vs 0.43; rate ratio [95% CI]: 0.67 [0.43, 1.04]; p=0.073). Severe exacerbation rates were numerically reduced with FF/UMEC/VI versus BUD/FOR treatment across both subgroups. FF/UMEC/VI conferred significant improvements in lung function and health status versus BUD/FOR, regardless of recent exacerbation history.Conclusion: FF/UMEC/VI reduced moderate/severe and severe exacerbation rates and improved lung function and health status versus BUD/FOR in patients with symptomatic COPD, regardless of recent exacerbation history.Keywords: COPD, exacerbations, severe exacerbations, triple therapy, ICS/LABA
