ABSTRACT
Background: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), a triple CFTR modulator combination, has proved to be highly effective in Phe508del homozygous and Phe508del/minimal function compound heterozygous people with cystic fibrosis (PwCF).We report preliminary data on the realworld effectiveness and safety of ELX/TEZ/IVA after 6 months of treatment. Method(s):We collected prospective data on PwCF who started ELX/TEZ/IVA and evaluated changes in pulmonary function (spirometry and lung clearance index [LCI]), nutritional status (body mass index [BMI]), sweat chloride, and rate of hospitalization from baseline to 6 months of treatment. Result(s): Between August 2021 and October 2021, ELX/TEZ/IVAwas started in 24 PwCF (12 female,10 Phe508del-homozygous, median age 20.5 (range 13-37), all with pancreatic insufficiency). After 6 months of treatment, all respiratory function indicators improved (median change: +16% percentage predicted forced expiratory volume in 1 second, +12% percentage predicted forced vital capacity, +23% percentage predicted forced expiratory flow at 25/75%, -2 lung clearance index). Improvement was also observed in BMI (+0.41 z-score) and sweat chloride concentrations (-54 mMol/L, 6 PwCF had Cl concentrations within the limit of normality) (Table 1). Over a 6-month period, only one hospitalization due to pulmonary exacerbations was observed, compared with 22 hospitalizations observed in the 6 months before starting ELX/TEZ/IVA (rate per 100 patient-months 15.3 vs 0.7, rate ratio 0.05, 95% CI, 0.01-0.29). Treatment was well tolerated, with only mild and transient adverse events consisting of headache (n = 4), cutaneous rash (n = 2), and mild hemoptysis (n = 2). One PwCF had intestinal subocclusion and required hospitalization. One patient had liver function test elevation after 6 months of therapy during an Changes in clinical variables and sweat test results from baseline through 6 months in patients treated with elexacaftor, tezacaftor and ivacaftor. Data are medians (interquartile ranges). Baseline vs 6 months compared usingWilcoxon signed-rank test. ppFEV1, percentage predicted forced expiratory volume in 1 second;ppFVC, percentage predicted forced vital capacity;ppFEV25/75, percentage predicted forced expiratory flow at 25/75%;LCI, lung clearance index;BMI, body mass index;Cl, chloride. (Table Presented) episode of SARS-COV2 infection, which required adjustment of the dose administered. Conclusion(s): Our data confirm that ELX/TEZ/IVA treatment is safe, well tolerated, and effective in PwCF. ELX/TEZ/IVA improved pulmonary function and nutritional status and remarkably reduced hospitalization rate. Our data indicate that introduction of ELX/TEZ/IVA in CF care will radically change the natural history of and management approach to the disease.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved