(572) Changes in total IgE levels and fungal acquisition in People with CF before and after Elexacaftor/Tezacaftor/Ivacaftor Initiation

Background: While bacterial infections are a hallmark of the disease, CF is commonly associated with fungi, atopy, asthma, and allergic bronchopulmonary aspergillosis. This is thought to be due to allergens and fungal spores being captured by viscous mucus, however studies are limited. Ivacaftor alone has shown reduction in Aspergillus detection and recently, elexacaftor/tezacaftor/ivacaftor (ETI) was shown to improve mucus viscosity and mucus clearance as well as reduce bacteria load in sputum. Given this, we hypothesized that increasing ETI use would change fungal detection in people with CF (PwCF) and consequently lower allergic IgE response

Methods: We conducted a single center retrospective analysis of PwCF using the CF Registry to identify cases from the UAB pediatric center cohort. Medical record data extraction included total IgE, environmental allergy results, Aspergillus and Scedosporium from registry, culture results, other metrics, ETI use and dispensing information from 2010-2021.

Results: After data extraction, 12 individuals were included in the study given that they had a dx of CF, at least one IgE >500 during time frame, and at least one IgE value Pre and Post ETI. Median age for Pre-ETI IgE value was 15 years old. In all subjects (regardless of ABPA diagnosis) we observed a significant reduction in total IgE level after ETI was initiated in those with an IgE level >500 prior to ETI use. The reduction in IgE from baseline was significant at one year and greater than one year post ETI initiation, when compared to IgE levels the year prior to ETI initiation, controlling for the potential of regression to the mean (p=0.02, 0.04 respectively). IgE levels were stable greater than a year prior to ETI initiation (Figure). Evaluating changes in anyone with a hx of abnormal IgE and on ETI is underway. Pediatric center specific CF registry data supplemented by chart review and random screening during Fall 2021 showed that in people with CF that had both positive fungal cultures and ETI use, the number of positive fungal cultures (Aspergillus, Scedosporium, and mold) decreased as the number of individuals on ETI increased. The majority of individuals (16 of 28 from 2010-2021) last isolated fungi in 2018-2019. Interestingly, 10 individuals started ETI this same period (2018-2019) and 13 individuals started ETI in 2020-2021, while only 5 individuals isolated fungi that same period (2020-2021). Further screening is underway.

Conclusions: In PwCF with high IgE, ETI use is associated with reduced serum IgE that is sustained for one year. This suggests ETI is altering atopic response, regardless of ABPA diagnosis. Fungal acquisition followed a similar trend. Reduced fungi infection, rather than problems with its detection, may be occurring with CFTR modulator therapy. Larger prospective studies are needed evaluate the effect of ETI on atopy in PwCF.

Acknowledgements: This work is supported by the Cystic Fibrosis Foundation (POORE20D0), UAB CF Research and Translation Core Center – (P30DK072482) and UAB Research and Development Program (CFF, ROWE19RO)

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