Fernando J Martinez1, Leonardo M Fabbri2, Gary T Ferguson3, Chad Orevillo4, Patrick Darken5, Ubaldo J Martin6, Colin Reisner7. 1. Joan and Sanford Weill Department of Internal Medicine, Weill Cornell Medicine, New York, NY. Electronic address: fjm2003@med.cornell.edu. 2. Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy. 3. Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI. 4. Former employee of Clinical Development, Pearl Therapeutics, Inc, Morristown, NJ. 5. Department of Biostatistics, Pearl Therapeutics, Inc, Morristown, NJ. 6. Respiratory Global Medicines, AstraZeneca, Gaithersburg, MD. 7. Clinical Development and Medical Affairs, Pearl Therapeutics, Inc, Morristown, NJ; and Respiratory Global Medicines, AstraZeneca, Gaithersburg, MD.
Abstract
BACKGROUND: The clinical severity of COPD is currently categorized by symptom burden and exacerbation risk. Previous 24-week phase III trials (NCT01854645 and NCT01854658) that demonstrated better improvement of lung function with glycopyrrolate/formoterol fumarate (GFF) metered dose inhaler (MDI) (an MDI fixed-dose of GFF 18/9.6 μg) over individual monocomponent MDIs included a cross-section of patients with moderate to very severe airflow limitation and a broad range of COPD symptoms. METHODS: These post hoc analyses of pooled data investigated whether baseline symptom burden, assessed using the COPD Assessment Test (CAT) score, impacted GFF MDI-associated improvements in lung function, health status, rescue medication use, and exacerbation risk. RESULTS: In 3,699 patients, improvement in FEV1 at week 24 between the GFF MDI and monocomponent MDIs and a placebo MDI was similar in magnitude regardless of baseline CAT score. In contrast, the magnitude of mean difference in the St. George's Respiratory Questionnaire total score for GFF MDI vs monocomponent MDIs and the placebo MDI increased with increasing baseline CAT scores. Likewise, reduced rescue medication use and lower exacerbation risk were more pronounced in GFF MDI groups with a higher baseline symptom burden. CONCLUSIONS: Beneficial effects of GFF MDI on health status, rescue medication use, and exacerbation risk in symptomatic patients with COPD increased as a function of baseline symptom burden, whereas lung function benefits were independent. These data suggest a greater clinical benefit from dual bronchodilators in symptomatic patients than in patients without symptoms. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01854645 and NCT01854658; URL: www.clinicaltrials.gov.
RCT Entities:
BACKGROUND: The clinical severity of COPD is currently categorized by symptom burden and exacerbation risk. Previous 24-week phase III trials (NCT01854645 and NCT01854658) that demonstrated better improvement of lung function with glycopyrrolate/formoterol fumarate (GFF) metered dose inhaler (MDI) (an MDI fixed-dose of GFF 18/9.6 μg) over individual monocomponent MDIs included a cross-section of patients with moderate to very severe airflow limitation and a broad range of COPD symptoms. METHODS: These post hoc analyses of pooled data investigated whether baseline symptom burden, assessed using the COPD Assessment Test (CAT) score, impacted GFF MDI-associated improvements in lung function, health status, rescue medication use, and exacerbation risk. RESULTS: In 3,699 patients, improvement in FEV1 at week 24 between the GFF MDI and monocomponent MDIs and a placebo MDI was similar in magnitude regardless of baseline CAT score. In contrast, the magnitude of mean difference in the St. George's Respiratory Questionnaire total score for GFF MDI vs monocomponent MDIs and the placebo MDI increased with increasing baseline CAT scores. Likewise, reduced rescue medication use and lower exacerbation risk were more pronounced in GFF MDI groups with a higher baseline symptom burden. CONCLUSIONS: Beneficial effects of GFF MDI on health status, rescue medication use, and exacerbation risk in symptomatic patients with COPD increased as a function of baseline symptom burden, whereas lung function benefits were independent. These data suggest a greater clinical benefit from dual bronchodilators in symptomatic patients than in patients without symptoms. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01854645 and NCT01854658; URL: www.clinicaltrials.gov.
Authors: Fernando J Martinez; Brian J Lipworth; Klaus F Rabe; David J Collier; Gary T Ferguson; Sanjay Sethi; Gregory J Feldman; Gerald O'Brien; Martin Jenkins; Colin Reisner Journal: Respir Res Date: 2020-05-25
Authors: Alexander J Mackay; Konstantinos Kostikas; Nicolas Roche; Stefan-Marian Frent; Petter Olsson; Pascal Pfister; Pritam Gupta; Francesco Patalano; Donald Banerji; Jadwiga A Wedzicha Journal: Respir Res Date: 2020-04-22
Authors: Fernando J Martinez; Klaus F Rabe; Brian J Lipworth; Samir Arora; Martin Jenkins; Ubaldo J Martin; Colin Reisner Journal: Int J Chron Obstruct Pulmon Dis Date: 2020-01-09
Authors: Claus F Vogelmeier; Edward M Kerwin; Leif H Bjermer; Lee Tombs; Paul W Jones; Isabelle H Boucot; Ian P Naya; David A Lipson; Chris Compton; Neil Barnes; François Maltais Journal: Ther Adv Respir Dis Date: 2020 Jan-Dec Impact factor: 4.031