Risk of Hospitalized COVID ‐19 in COPD : Single‐Inhaler Triple Versus Dual Bronchodilator Therapy

ABSTRACT Purpose Our objective was to estimate the effect of initiating an inhaled corticosteroids‐containing single‐inhaler triple agent (ICS‐LABA‐LAMA) compared with a single‐inhaler LABA‐LAMA dual bronchodilator in patients with COPD on the risk of severe COVID‐19 prior to the roll‐out of vaccines. Methods We conducted a cohort study emulating a randomized trial, among patients with COPD aged 40 years or more in the UK, comparing those who initiated a triple inhaler with those who initiated a dual bronchodilator inhaler between March 1 and December 31, 2020. Weighting by fine stratification of the propensity score was used to account for confounders. The risk of hospitalized COVID‐19 was compared with a Cox proportional hazards model in an as‐treated analysis with a 30‐day grace period. Results The study cohort included 876 patients initiating a triple inhaler and 5010 initiating a dual LABA‐LAMA inhaler. The adjusted incidence rate of hospitalized COVID‐19 was 5.6 per 100 person‐years in the triple inhaler group and 2.9 per 100 person‐years in the dual inhaler group, with a corresponding hazard ratio (HR) of 1.96 (95% confidence interval 1.01–3.77). Sensitivity analyses on the duration of the grace period, using an intent‐to‐treat exposure classification, or starting follow‐up 14 days after treatment initiation (accounting for treatment initiation for an undocumented SARS‐CoV‐2 infection) were generally consistent with the main analysis. Conclusions Patients with COPD prescribed an ICS‐containing triple inhaler were potentially exposed to an increased risk of severe COVID‐19 prior to the vaccine era. As SARS‐CoV‐2 continues to cause significant burden, these findings should be considered when determining initiation of inhaled treatment in COPD.