OBJECTIVES: Patients with symptomatic COPD and frequent exacerbations typically receive combination therapy involving inhaled corticosteroids (ICS), long-acting beta agonist (LABA) and/or long-acting muscarinic antagonist (LAMA). While pivotal randomized controlled trials have demonstrated lower exacerbation rates with ICS versus non-ICS therapy, recent RWE studies have failed to replicate these findings, likely due to insufficient confounder data or use of less robust analytic methods. This study aims to obtain real-world evidence on the benefits of ICS-containing COPD maintenance therapy, using double-robust Longitudinal Targeted Maximum Likelihood Estimation (L-TMLE).

METHODS: A retrospective cohort study was executed using population-wide administrative data of COPD patients in Alberta, who were dispensed a long-acting COPD maintenance therapy between 1-April-2014, to 31-March-2019. The first dispense in that time-period was the index date and time zero for a 6-month follow-up period. A longitudinal TMLE model was used, with the 6-months follow-up period, subdivided into 15-day intervals. Using an intention-to-treat analysis, the first long-acting therapy combination in each interval was considered the treatment. The parameter of interest was the average treatment effect (ATE), the mean difference in rates of exacerbations if patients were always given ICS+LABA+LAMA compared to if they were always given LABA+LAMA. Exacerbations were categorized as moderate (outpatient visit with a diagnosis code for COPD and a dispense of oral corticosteroids or an antibiotic for respiratory infection within 5 days of the visit, for <15 days) or severe (emergency department visit with a COPD diagnosis in any position or a hospitalization with a “most-responsible diagnosis” or post-admission COPD code).

RESULTS: Overall, 89,296 patients were included in the analysis. The preliminary estimate of ATE was -0.32(-0.48, -0.17) for severe or moderate exacerbations, -0.13(-0.23, -0.02) for severe and -0.16(-0.27, -0.05) for moderate exacerbations.

CONCLUSIONS: Results from this study show evidence of real-world benefits of ICS-containing COPD maintenance therapy to prevent future exacerbations.