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Exploring reduced pulmonary exacerbation rates in cystic fibrosis: a pandemic or modulator effect?
Anne L Stephenson1, Jenna Sykes1, Sanja Stanojevic2
1Division of Respirology, St Michael's Hospital, University of Toronto, ON, Canada.
Background:
The impact of elexacaftor-tezacaftor-ivacaftor (ETI) on pulmonary exacerbations (PEx) in cystic fibrosis (CF) is difficult to estimate since ETI availability coincided with the COVID-19 pandemic. Later access to ETI in Canada created a natural experiment to adjust for the impact of the pandemic on PEx rates. The objective for this study was to compare PEx rates pre- and post-ETI in the USA using Canada as a control group.
Methods:
This retrospective cohort study utilised data from the US and Canadian CF patient registries from 1 January 2015 to 31 December 2022. Individuals with at least one F508del mutation and ≥12 years old were followed. Poisson regression was used to estimate PEx rates per 100 person-years of follow-up. A difference-in-difference approach was used to estimate the impact of ETI alone.
Results:
Longitudinal data from 22 590 US individuals and 3271 Canadians were analysed. Pre-pandemic, the PEx rate was significantly higher in the USA (70.6, 95% CI 70.1-71.2) compared to Canada (53.1, 95% CI 51.9-54.3). During the COVID-19 pandemic, the PEx rate decreased to 30.2 (95% CI 28.8-31.8) in Canada; whereas in the USA, the rates decreased to 14.7 (95% CI 14.3-15.1). After adjusting for covariates, the ETI effect was 2.48 times (95% percentile interval 2.26-2.70) that of the pandemic effect.
Conclusions:
Public health measures imposed during the pandemic resulted in a reduction in the number of PEx for both countries; however, the impact of ETI on reducing the rate of PEx was more than double the effect of the COVID-19 pandemic.
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