WS08.02Specific Pseudomonas aeruginosa IgG levels before and after elexacaftor/tezacaftor/ivacaftor treatment

PA lung infection is a significant concern in people with cystic fibrosis (pwCF). Close monitoring with sputum samples is international standard, however this system of monitoring has become difficult after the introduction of elexacaftor/tezacaftor/ivacaftor (ETI). In Denmark, routine analysis of specific PA immunoglobulin G (IgG) is used in combination with sputum samples. In this study we sought to examine specific PA IgG levels before and after ETI treatment among PA infected pwCF.

Data on IgG, modulator treatment and pulmonary infections were extracted from the Danish Cystic Fibrosis Cohort and national microbiology database. Data was grouped into four distinct time periods: One year before ETI initiation and the first, second and third year after. Based on sputum microbiology results, all individuals were grouped in accordance with Leeds criteria at each time period. A linear mixed effects model was used to estimate IgG levels.

236 pwCF were included. Distribution before ETI according to Leeds criteria was ‘never infected’ 22 (9,3%), ‘infection free’ 103 (44%), ‘intermittent’: 39 (17%) and ‘chronic’: 72 (31%). Among the 39 intermittently infected 24 shifted to ‘infection free’ but IgG was unchanged with a difference of 0.6 ELISA units (-0.7; 2.0). Among the 72 chronically infected 19 dropped at least one level on Leeds criteria by year 3 while IgG decreased 2.0 ELISA units 95% CI (1.0; 3.0).

Our findings suggest that the use of IgG levels with conventional sputum analysis offers insights into the dynamics of PA infection status post-ETI. Among chronically infected individuals, a significant decrease in IgG levels was observed three years following ETI initiation, indicative of a reduction in bacterial load. Conversely, in intermittently infected individuals, no significant change in specific IgG levels was noted despite a large decrease in number of isolated PA, highlighting the need for continued vigilance in monitoring PA despite clinical stability.