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

囊性纤维化患者接受 elexacaftor/tezacaftor/ivacaftor 治疗后发生呼吸道感染:欧洲囊性纤维化协会患者登记分析

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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.

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