Respiratory infections after elexacaftor/tezacaftor/ivacaftor treatment in people with cystic fibrosis: analysis of the European Cystic Fibrosis Society Patient Registry

Abstract

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has improved outcomes for people with cystic fibrosis (pwCF). This study evaluated changes in airway microbiological infection status after initiating ETI.

Methods: Using the European Cystic Fibrosis Society registry, pwCF who started ETI between 2019 and 2021 were identified. The changes in microbiological status from 1 year before to 1 year after ETI initiation, were compared with the changes seen from 3 to 1 years before starting ETI. Mixed-effect regression models were used to analyse changes. Data from 2 years after initiation were examined for those starting ETI in 2019-2020.

Results: Included were 15 739 pwCF from 30 countries. In the year before ETI, 38.4% were positive for Pseudomonas aeruginosa (PsA) and 36.4% for methicillin-sensitive Staphylococcus aureus (MSSA). After ETI, 38.7% of PsA-positive and 47.2% of MSSA-positive patients transitioned to negative status, compared with 14.8% and 29.1%, respectively, in the previous years. The adjusted difference in transitioning to negative was 14.6% (PsA) and 17.1% (MSSA), both p<0.001. Similar improvements were seen for Burkholderia cepacia complex and Stenotrophomonas maltophilia. For those starting ETI in 2019-2020, PsA positivity remained low over 2 years, decreasing from 46.8% pre-ETI to 30.4% and 27.7% at 1 and 2 years after ETI treatment.

Conclusion: One year after starting ETI, many pwCF who were initially positive for various CF-related pathogens, shifted to a negative status, a change less common before ETI. These findings suggest that ETI reduces airway infections, with benefits extending into the second year of treatment, although some pwCF continue to carry these pathogens despite treatment.

FIGURE 1

Study timeline. The considered time points for the analysis are shown. “Pre to post” defines the time comprising 1 year before (−1) and after (+1) elexacaftor/tezacaftor/ivacaftor (ETI) initiation (0). “Pre to pre” defines the years before treatment: 3 (−3) and 1 (−1) year before ETI initiation. For those starting ETI in 2019 and 2020 (n=7973) data from the second year after ETI were included.

FIGURE 2

Proportion of positive microbiological status at considered time points. Bars denote the proportion of people with cystic fibrosis with positive microbiological status at considered time points. Specific numbers and percentages for the different time points can be seen in supplementary table S2. ETI: elexacaftor/tezacaftor/ivacaftor.

FIGURE 3

Alluvial plots: Pseudomonas aeruginosa status at all time points . Stacked bars denote the percentage of people with cystic fibrosis (pwCF) with a) positive/negative P. aeruginosa and b) methicillin-sensitive Staphylococcus aureus (MSSA) at different time points. Colours identify pwCF with positive/negative bacterial detection 3 years before elexacaftor/tezacaftor/ivacaftor (ETI). The flow streams show how their frequency changed from 3 years before ETI through 1 year after exposure to ETI.

FIGURE 4

Proportion of positive microbiological status for those starting elexacaftor/tezacaftor/ivacaftor (ETI) in 2019/2020 and with 2 years of follow-up. Bars denote proportion of positive microbiological status for those starting ETI in 2019/2020 with continuous follow-up from −1 to +2 years after ETI. Specific numbers and percentages for the different time points can be seen in supplementary table S4.