Chest
Volume 155, Issue 6, June 2019, Pages 1158-1165
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Original Research: COPD
Comparative Effectiveness and Safety of LABA-LAMA vs LABA-ICS Treatment of COPD in Real-World Clinical Practice

https://doi.org/10.1016/j.chest.2019.03.005Get rights and content

Background

Long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are recommended as initial maintenance treatments for COPD, with their combination (LABA-LAMA) advocated as the disease progresses. Randomized trials comparing the effectiveness of this combination with the alternative combination of LABA with inhaled corticosteroid (LABA-ICS) have reported conflicting data, while there are no real-world comparative effectiveness and safety studies of these regimens in clinical practice settings.

Methods

We identified a cohort of patients with COPD during 2002-2015, age 55 years or older, from the United Kingdom’s Clinical Practice Research Datalink. Patients initiating LABA-LAMA on the same day (no ICS) were matched on time-conditional high-dimensional propensity scores with patients initiating LABA-ICS on the same day (no LAMA), and monitored for 1 year for the occurrence of a moderate or severe COPD exacerbation and severe pneumonia.

Results

The cohort included 1,977 initiators of LABA-LAMA matched with 1,977 initiators of LABA-ICS. The hazard ratio (HR) of moderate or severe COPD exacerbation associated with LABA-LAMA initiation, relative to LABA-ICS initiation, was 1.04 (95% CI, 0.90-1.20), while for a severe exacerbation it was 0.94 (95% CI, 0.65-1.36). The incidence of severe pneumonia requiring hospitalization was lower with LABA-LAMA initiation (HR, 0.66; 95% CI, 0.41-1.05), particularly in the on-treatment analysis (HR, 0.66; 95% CI, 0.50-0.87).

Conclusions

In a real-world clinical practice setting of COPD treatment, combined LABA-LAMA inhalers appear to be as effective as combined LABA-ICS inhalers in preventing COPD exacerbations. However, a LABA-LAMA combination may be preferred because it is associated with fewer severe pneumonias.

Section snippets

Data Source

This study was conducted using the Clinical Practice Research Datalink (CPRD), a primary care database from the United Kingdom that contains primary care medical records for over 10 million people enrolled from over 600 practices. Trained participating general practitioners record medical information, including demographic data, lifestyle factors, and medical diagnoses, using the Read classification. Prescriptions are automatically transcribed, using the UK Prescription Pricing Authority

Results

The base cohort included 56,460 patients with a diagnosis of COPD and a prescription for LABA, LAMA, or ICS from January 1, 2002 to December 31, 2015, after excluding patients with a diagnosis of asthma and less than 55 years of age (Fig 1). There were 2,066 initiators of LABA-LAMA on the same date at some point during follow-up. After computing time-conditional propensity score, 1,977 initiators of LABA-LAMA were matched to 1,977 initiators of LABA-ICS. The baseline characteristics of these

Discussion

In this observational study in the real-world setting of COPD treatment, we found that patients treated with a LABA and a LAMA, both as initial treatment or adding one to the other, have a similar incidence of exacerbations as those treated with a LABA and an ICS, over the first year of use. There was a trend for a higher incidence of exacerbation with LABA-LAMA in patients with a > 6% blood eosinophil count. However, the incidence of pneumonia was lower with the LABA-LAMA treatment. This is

Acknowledgments

Author contributions: P. E. participated in study design, data interpretation, and writing of the manuscript. S. D’A. participated in data analysis and writing of the manuscript. S. S. participated in data acquisition, study design, data interpretation, and writing of the manuscript, and acts as guarantor of this entire manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: S. S. has received research grants from Boehringer Ingelheim and Novartis and

References (25)

  • J.A. Wedzicha et al.

    FLAME Investigators. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD

    N Engl J Med

    (2016)
  • D. Singh et al.

    Umeclidinium/vilanterol versus fluticasone propionate/salmeterol in COPD: a randomised trial

    BMC Pulmon Med

    (2015)
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    FUNDING/SUPPORT: This research was funded in part by grants from the Canadian Institutes of Health Research (CIHR) [Grant No. CIHR MOP-49462], the Canada Foundation for Innovation (CFI) [Grant No. CFI 94480], and Boehringer-Ingelheim. S. S. is the recipient of the James McGill Professorship award.

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