ERJ open research · 2026
Off-label treatment with elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: real-world evidence from the German CF Registry.
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Stahl Mirjam, Gerts Florian S, Hafkemeyer Sylvia, Wosniok Julia, Naehrlich Lutz, German CF Registry of the Mukoviszidose e.V. and participating sites
Аннотация
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.
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.