(128) Sex-based differences in cystic fibrosis pulmonary exacerbations: Sub-analysis of the STOP2 cohort

Background: Data have shown that females with CF have higher morbidity and mortality compared to males, yet evaluations of differences in clinical trials outcomes by sex in CF are limited. Utilizing the Standardized Treatment of Pulmonary Exacerbations-2 (STOP2) cohort, we examined sex-based differences in pulmonary exacerbation (PEx) outcomes in people with CF treated with intravenous (IV) antibiotics.

Methods: STOP2 was a multi-center, randomized, controlled, clinical trial of treatment duration in adults with CF who received IV antibiotics for a PEx conducted from July 2016 through January 2020. Participants were randomized to 10 vs 14-day antimicrobial duration (early robust responder) if they demonstrated pre-defined lung function and symptom improvements after 7-10 days of treatment or were randomized to 14 vs 21-day duration (non-early robust responders). Aligning with STOP2, our primary outcome was the difference between sexes in absolute change in ppFEV1 from treatment initiation (Visit 1 (V1)) to two weeks after IV antibiotics (Visit 3 (V3)) using multivariable linear regression models adjusted for trial stratification variables and a priori demographic and clinical characteristics. Secondary endpoints included respiratory symptom scores (CRISS), weight, time to next PEx and adverse events (AE).

Results: A total of 982 participants were randomized and comprised the intention to treat population, of which 496 (50.5%) were females. Overall, females were more likely to have had an IV-treated PEx in the prior year, have a higher maximum and average baseline ppFEV1 in the prior year, and were more likely to be prescribed steroids during STOP2 compared to males. We found no sex differences in mean ppFEV1 decline from 6-month pre-study baseline to V1 (difference: 1.16; 95% CI: -0.07, 2.40). Females had a significantly higher mean ppFEV1 (52.7% vs. 47.0%, p< 0.001) at V1, but there was no difference in ppFEV1 change from V1 to V3 between sexes (difference: -0.73; 95% CI: -1.78, 0.33). Similarly, CRISS scores were significantly higher (worse) for females compared to males at study enrollment (52.3 vs 49.2, p< 0.001) but there was no statistically significant difference in CRISS score change from V1 to V3 between sexes (difference: -0.27; 95% CI: -1.94, 1.41). Females gained less weight from V1 to V3 (difference between groups -0.73 kg; 95% CI: -1.04, -0.42) and had a higher risk for a subsequent IV-treated PEx (HR 1.26; CI: 1.07, 1.47) compared to males. We found no difference in AE (any or serious) by sex. Results were generally consistent within the ERR and NERR study arms.

Conclusions: Our results suggest sex-related differences in PEx presentation. Females started with a higher lung function at treatment initiation, yet reported worse respiratory symptoms compared to males. While we found no sex difference in lung function or respiratory symptoms after IV antibiotic treatment, female sex was associated with an increased risk for future IV-treated PEx. Understanding sex disparities in CF remains a priority for the CF community and needs to be further explored in relation to highly effective modulator therapy.

Acknowledgements: This work was supported by the Cystic Fibrosis Foundation (MONTEMQ020).

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