Baseline Symptom Score Impact on Benefits of Glycopyrrolate/Formoterol Metered Dose Inhaler in COPD

Chest. 2017 Dec;152(6):1169-1178. doi: 10.1016/j.chest.2017.07.007. Epub 2017 Jul 16.

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.

Keywords: bronchodilators; chronic bronchitis; combination therapy; emphysema; metered dose inhalers.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Adult
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Forced Expiratory Volume / drug effects
  • Formoterol Fumarate / administration & dosage*
  • Glycopyrrolate / administration & dosage*
  • Humans
  • Male
  • Metered Dose Inhalers*
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Drug Combinations
  • Muscarinic Antagonists
  • Glycopyrrolate
  • Formoterol Fumarate

Associated data

  • ClinicalTrials.gov/NCT01854645
  • ClinicalTrials.gov/NCT01854658