A76-22 Sex Differences in Clinical Outcomes Among Adults With Cystic Fibrosis After Initiation of Elexacaftor/Tezacaftor/Ivacaftor: Analysis From a Multi-center Prospective Study

Abstract Rationale Sex disparities among persons with cystic fibrosis (PwCF) are well documented prior to cystic fibrosis transmembrane conductance regulator modulators (CFTRm), with females having lower pulmonary function, increased rates of pulmonary exacerbations (PEx) and chronic infection with Pseudomonas aeruginosa (PsA). While overall survival for males and females improved in the era of CFTRm, the extent to which a sex disparity persists is unknown. This study aims to compare clinical outcomes between males and females up to 30 months after initiation of elexacaftor/tezacaftor/ivacaftor (ETI). Methods PROMISE is a multicenter prospective study of PwCF 12y started on CFTRm. Data were collected prior to and 1, 3, 6, 18, and 30 months after ETI initiation. Outcomes included mean percent-predicted FEV1 (ppFEV1), body mass index (BMI), cystic fibrosis questionnaire revised-respiratory domain (CFQ-R) score, sweat chloride, and prevalence of PsA. Mean PEx were compared between 2017-18 and 2022-23 to minimize variability from COVID-19. We conducted longitudinal data analysis using generalized estimating equation method for each outcome variable, adjusting for age and prior non-ETI modulator use; interactions between sex and time were used to test if changes differed by sex. Results 158 females and 154 males 18y were included. No statistically significant sex differences were found in mean changes in ppFEV1, BMI, and CFQ-R over 30mos. Month-12 sweat chloride was lower for both females (mean difference -46.2 mmol/L; 95% CI -49.6, -42.7) and males (mean difference -38.5 mmol/L; 95% CI -41.8,-35.3) with females experiencing greater reduction (p 0.001 for interaction effect over time). Both sexes experienced significant decline in PsA infection at 6-30 months (males 11%, females 12%) compared to baseline (female OR = 0.07; 95% CI 0.04,0.13, male OR = 0.18; 95% CI 0.10,0.32). Declines in PEx did not differ significantly between sexes; however, among people with baseline ppFEV150 (25 females, 23 males), males had lower incidence of PEx (mean 0.41 vs 0.98, rate ratio=0.42; 95% CI 0.19,0.93) and greater reduction (p 0.05 for interaction effect) post-ETI. Conclusions Overall, our results did not suggest statistically significant sex differences in clinical outcomes among adults with CF 2y after ETI. Females did experience greater reduction in sweat chloride, although the clinical significance of this finding remains unknown. Ongoing work in this cohort includes testing relationships of sex hormones with clinical outcomes and inflammatory markers. Long-term studies to assess sex disparities in mortality are also warranted. Acknowledgements: We thank the CF Foundation and Therapeutics Development Network for use of this data. This abstract is funded by: none