Differences in pulmonary exacerbation risks among CF subpopulations

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BACKGROUND: Studies of CF therapies intended to reduce pulmonary exacerbations (PEx) balance future PEx risks across treatment groups. Recent PEx definitions capture any antimicrobial treatments, but future PEx risks using newer definitions and among people with CF (pwCF) receiving elexacaftor/tezacaftor/ivacaftor (ETI) remain undescribed. METHODS: PwCF 12+ years followed in the CF Foundation Patient Registry (CFFPR) receiving either no modulators or ETI in 2022-2023 were studied. 2022 PEx frequency was stratified (zero, one or two, or three+); mean 2023 PEx frequencies and time to first 2023 PEx were determined. 2023 PEx hazards were modeled using 2022 PEx frequency, lung disease stage, age, sex, Pseudomonas aeruginosa infection status, and treatment (no modulator, ETI). RESULTS: Among 2188 not receiving modulators, 62.7 %, 28.1 %, and 9.2 % had no, one or two, and three+ PEx in 2022, respectively, as did 73.1 %, 23.6 %, and 3.2 % of 14,964 receiving ETI. Mean 2023 PEx frequencies were strongly associated with 2022 PEx frequencies. Time to first 2023 PEx varied by 2022 PEx frequency (P < 0.0001). After adjustment, pwCF with three+ 2022 PEx had a 7.11-fold higher hazard [95 % CI 6.44, 7.86]) and those with one or two 2022 PEx had a 2.89-fold higher hazard [2.72, 3.08] of PEx in 2023 than those with no PEx in 2022. DISCUSSION: Prior-year PEx frequency (treated by any route) was strongly associated with future PEx risk independent of modulator use. Although ETI reduces PEx rates, agents intended to further reduce rates can be studied in pwCF receiving ETI having experienced higher numbers of prior-year PEx.

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