Discontinuation of therapy among COPD patients who experience an improvement in exacerbation status

Eur J Clin Pharmacol. 2019 Jul;75(7):1025-1032. doi: 10.1007/s00228-019-02667-4. Epub 2019 Mar 22.


Purpose: A subset of patients with chronic obstructive pulmonary disease (COPD) experience a decrease in exacerbation frequency, leading to a diminished need for treatment with inhaled corticosteroids (ICS). We investigated prescribing and discontinuation patterns of long-acting bronchodilators and ICS in COPD patients according to exacerbation frequency.

Methods: Using the nationwide Danish health registries, we conducted a drug utilization study among patients who had at least two exacerbations or one hospitalization due to an exacerbation during 2011-2012. This study population was stratified according to consistency of exacerbation occurrence after 12, 24, 36, and 48 months of follow-up and the groups were described according to use of ICS, long-acting β2-agonists (LABA), and long-acting anticholinergics (LAMA), and combinations thereof.

Results: We identified 29,010 COPD exacerbators during 2011-2012. Upon inclusion, 70% received ICS-containing regimens, in combination with LABA (23%) or both LABA and LAMA (41%). The proportion of prevalent users of ICS-containing regimens decreased to 56% during follow-up among exacerbation-free individuals, while it increased to 86% in individuals who experienced at least one exacerbation annually. Persistence to ICS-containing regimens was 58% after 4 years in individuals without exacerbations compared to 74% among those with annual exacerbations. Similar patterns were observed for triple therapy which was the most extensively used drug combination regardless of consistency of exacerbation occurrence.

Conclusions: The extensive use of ICS and the relatively high persistence to ICS-containing regimens in individuals who had a decrease in exacerbation occurrence highlight a need for the development and implementation of de-escalation strategies in clinical practice.

Keywords: COPD; Inhaled corticosteroids; Long-acting bronchodilators; Pharmacoepidemiology; Utilization patterns.

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / therapeutic use
  • Adrenergic beta-2 Receptor Agonists / therapeutic use
  • Aged
  • Aged, 80 and over
  • Denmark
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Hospitalization
  • Humans
  • Male
  • Muscarinic Antagonists / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Severity of Illness Index
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Muscarinic Antagonists