Work

Off-label treatment with elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: real-world evidence from the German CF Registry

Year: 2025

Type: article

Abstract: Background Elexacaftor/tezacaftor/ivacaftor (ETI) triple therapy has been introduced as causal therapy for people with cystic fibrosis (pwCF) carrying at least one F508del allele. Data on the real-world effect of ETI in pwCF without any F508del allele are limited. Methods In this observational cohort study, data from the German CF Registry for pwCF who received off-label ETI for up to 365 days were used to study effects on lung function, nutritional status and sweat chloride concentration (SCC). Results 616 pwCF (mean± sd age 28.8±13.9 years) were registered with ETI treatment within compassionate use (n=509; at least one F508del allele present) or off-label use (carrying non- F508del mutations likely to respond to ETI (n=81) or not (n=26)). After 1 year, mean percentage predicted forced expiratory volume in 1 s increased by 10.3±11.0 (p<0.0001) and 9.0±10.7 (p<0.0001) percentage points compared to baseline in the at least one F508del and non- F508del predicted responsive groups, and remained stable in the non- F508del predicted non-responsive group (p=0.31). Body mass index percentile increased in the at least one F508del and non- F508del predicted responsive groups (11.4±15.2; p<0.0001 and 5.0±12.3; p<0.05, respectively), and remained stable in the non- F508del predicted non-responsive group (p=0.14). Mean SCC after 3 months decreased by 43.9±24.6 mmol·L −1 (p<0.0001) and 34.4±22.9 mmol·L −1 (p<0.0001), respectively, in the at least one F508del and non- F508del predicted responsive groups, and increased in the non- F508del predicted non-responsive group (14.8±9.5 mmol·L −1 ; p<0.05). Conclusions Real-world data align with the results of randomised clinical trials for pwCF carrying at least one F508del allele. Clinical improvements in pwCF with a range of CF transmembrane conductance regulator mutations treated off-label with ETI provide compelling support for the recent ETI label extension in Europe.

Source: ERJ Open Research

DOI: 10.1183/23120541.00667-2025

Authors: Mirjam Stahl, Florian S. Gerts, Sylvia Hafkemeyer, Julia Wosniok, Lutz Naehrlich, on behalf of the German CF Registry of the Mukoviszidose e.V. and participating sites