The effect of indacaterol/glycopyrronium versus tiotropium or salmeterol/fluticasone on the prevention of clinically important deterioration in COPD

Int J Chron Obstruct Pulmon Dis. 2017 May 4;12:1325-1337. doi: 10.2147/COPD.S133307. eCollection 2017.

Abstract

Background: Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD. In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.

Methods: Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC). Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD. Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George's Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation. In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.

Results: Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001). With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).

Conclusion: These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD. Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population.

Keywords: COPD; IND/GLY; deterioration.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Aged
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Clinical Trials, Phase III as Topic
  • Disease Progression
  • Drug Combinations
  • Endpoint Determination
  • Female
  • Fluticasone-Salmeterol Drug Combination / administration & dosage*
  • Fluticasone-Salmeterol Drug Combination / adverse effects
  • Forced Expiratory Volume
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / adverse effects
  • Glycopyrrolate / administration & dosage*
  • Glycopyrrolate / adverse effects
  • Humans
  • Indans / administration & dosage*
  • Indans / adverse effects
  • Kaplan-Meier Estimate
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage*
  • Muscarinic Antagonists / adverse effects
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Quinolones / administration & dosage*
  • Quinolones / adverse effects
  • Randomized Controlled Trials as Topic
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Time Factors
  • Tiotropium Bromide / administration & dosage*
  • Tiotropium Bromide / adverse effects
  • Treatment Outcome

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Drug Combinations
  • Fluticasone-Salmeterol Drug Combination
  • Glucocorticoids
  • Indans
  • Muscarinic Antagonists
  • Quinolones
  • indacaterol-glycopyrronium combination
  • Glycopyrrolate
  • Tiotropium Bromide