Arnaud Bourdin1, Gerard Criner2, Gilles Devouassoux3,4, Mark Dransfield5, David M G Halpin6, MeiLan K Han7, C Elaine Jones8, Ravi Kalhan9, Peter Lange10,11, Sally Lettis12, David A Lipson13,14, David A Lomas15, José M Echave-Sustaeta María-Tomé16, Neil Martin17,18, Fernando J Martinez19, Holly Quasny8, Lynda Sail20, Thomas M Siler21, Dave Singh22, Byron Thomashow23, Henrik Watz24, Robert Wise25, Nicola A Hanania26. 1. Department of Pneumology and Addictology, University of Montpellier, CHU Montpellier, Montpellier, France. 2. Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, United States. 3. Univ. Lyon, Université Claude-Bernard Lyon 1, Lyon, France. 4. Hôpital de la Croix-Rousse, Service de Pneumologie, Hospices Civils de Lyon, Lyon, France. 5. Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama, United States. 6. College of Medicine and Health, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom. 7. Pulmonary and Critical Care, University of Michigan, Ann Arbor, Michigan, United States. 8. GlaxoSmithKline, Research Triangle Park, North Carolina, United States. 9. Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States. 10. Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 11. Medical Department, Herlev University Hospital, Herlev, Denmark. 12. GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, United Kingdom. 13. GlaxoSmithKline, Collegeville, Pennsylvania, United States. 14. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States. 15. UCL Respiratory, University College London, London, United Kingdom. 16. Respiratory Department, Hospital Universitario Quirónsalud Madrid, Universidad Europea de Madrid, Madrid, Spain. 17. GlaxoSmithKline, Brentford, Middlesex, United Kingdom. 18. University of Leicester, Leicester, United Kingdom. 19. Weill Cornell Medicine, New York, New York, United States. 20. GlaxoSmithKline, Paris, France. 21. Midwest Chest Consultants, PC, St Charles, Missouri, United States. 22. The University of Manchester, Manchester University National Health Service Foundation Trust, United Kingdom. 23. Division of Pulmonary, Allergy, and Critical Care, Columbia University Medical Center, New York, New York, United States. 24. Pulmonary Research Institute at Lungen Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany. 25. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States. 26. Section of Pulmonary and Critical Care Medicine, Airways Clinical Research Center, Baylor College of Medicine, Houston, Texas, United States.
Abstract
BACKGROUND: The InforMing the Pathway of COPD Treatment (IMPACT) trial demonstrated lower moderate/severe exacerbation rates with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI or UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. Since IMPACT was a global study, post-hoc analyses were conducted by geographic region to investigate potential differences in overall findings. METHODS: IMPACT was a 52-week, randomized, double-blind trial. Patients with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25µg, FF/VI 100/25µg, or UMEC/VI 62.5/25µg. Endpoints assessed in the overall, Western Europe and North America populations included on-treatment moderate/severe exacerbation (rates and time-to-first), trough forced expiratory volume in 1 second and St George's Respiratory Questionnaire (SGRQ) total score. Safety was assessed. RESULTS: Overall, 10,355 patients were enrolled, 3164 from Western Europe, 2639 from North America. FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in Western Europe (rate ratios 0.82 [95%CI 0.74-0.91], P<.001 and 0.76 [0.67-0.87], P<.001) and in North America (0.87 [0.77-0.97], P=.014 and 0.69 [0.60-0.80], P<.001). FF/UMEC/VI reduced time-to-first moderate/severe exacerbation and improved lung function versus FF/VI and UMEC/VI in both regions, and improved SGRQ total score in Western Europe, but not North America. Safety profiles were generally similar between treatment groups/regions; the inhaled corticosteroid class effect of increased pneumonia incidence was seen in North America but not Western Europe. CONCLUSION: Consistent with intent-to-treat results, FF/UMEC/VI reduced moderate/severe exacerbation rate and risk and improved lung function in Western Europe and North America; however, between-regions differences were seen for SGRQ total score and pneumonia incidence. CLINICAL TRIAL REGISTRATION: NCT02164513. JCOPDF
BACKGROUND: The InforMing the Pathway of COPD Treatment (IMPACT) trial demonstrated lower moderate/severe exacerbation rates with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI or UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. Since IMPACT was a global study, post-hoc analyses were conducted by geographic region to investigate potential differences in overall findings. METHODS: IMPACT was a 52-week, randomized, double-blind trial. Patients with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25µg, FF/VI 100/25µg, or UMEC/VI 62.5/25µg. Endpoints assessed in the overall, Western Europe and North America populations included on-treatment moderate/severe exacerbation (rates and time-to-first), trough forced expiratory volume in 1 second and St George's Respiratory Questionnaire (SGRQ) total score. Safety was assessed. RESULTS: Overall, 10,355 patients were enrolled, 3164 from Western Europe, 2639 from North America. FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in Western Europe (rate ratios 0.82 [95%CI 0.74-0.91], P<.001 and 0.76 [0.67-0.87], P<.001) and in North America (0.87 [0.77-0.97], P=.014 and 0.69 [0.60-0.80], P<.001). FF/UMEC/VI reduced time-to-first moderate/severe exacerbation and improved lung function versus FF/VI and UMEC/VI in both regions, and improved SGRQ total score in Western Europe, but not North America. Safety profiles were generally similar between treatment groups/regions; the inhaled corticosteroid class effect of increased pneumonia incidence was seen in North America but not Western Europe. CONCLUSION: Consistent with intent-to-treat results, FF/UMEC/VI reduced moderate/severe exacerbation rate and risk and improved lung function in Western Europe and North America; however, between-regions differences were seen for SGRQ total score and pneumonia incidence. CLINICAL TRIAL REGISTRATION: NCT02164513. JCOPDF
Authors: David A Lipson; Frank Barnhart; Noushin Brealey; Jean Brooks; Gerard J Criner; Nicola C Day; Mark T Dransfield; David M G Halpin; MeiLan K Han; C Elaine Jones; Sally Kilbride; Peter Lange; David A Lomas; Fernando J Martinez; Dave Singh; Maggie Tabberer; Robert A Wise; Steven J Pascoe Journal: N Engl J Med Date: 2018-04-18 Impact factor: 91.245
Authors: David A Lipson; Helen Barnacle; Ruby Birk; Noushin Brealey; Nicholas Locantore; David A Lomas; Andrea Ludwig-Sengpiel; Rajat Mohindra; Maggie Tabberer; Chang-Qing Zhu; Steven J Pascoe Journal: Am J Respir Crit Care Med Date: 2017-08-15 Impact factor: 21.405
Authors: Anna E Wallace; Shuchita Kaila; Valentina Bayer; Asif Shaikh; Mayura U Shinde; Vincent J Willey; Mark B Napier; Joseph R Singer Journal: J Manag Care Spec Pharm Date: 2019-02
Authors: Monica J Fletcher; Jane Upton; Judith Taylor-Fishwick; Sonia A Buist; Christine Jenkins; John Hutton; Neil Barnes; Thys Van Der Molen; John W Walsh; Paul Jones; Samantha Walker Journal: BMC Public Health Date: 2011-08-01 Impact factor: 3.295
Authors: Sarah H Landis; Hana Muellerova; David M Mannino; Ana M Menezes; MeiLan K Han; Thys van der Molen; Masakazu Ichinose; Zaurbek Aisanov; Yeon-Mok Oh; Kourtney J Davis Journal: Int J Chron Obstruct Pulmon Dis Date: 2014-06-06