(664) Effectiveness and safety of elexacaftor-tezacaftor-ivacaftor therapy: an Italian center experience

Background: Elexacaftor-tezacaftor-ivacaftor (ETI), 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 real-world effectiveness and safety of ETI in patients after 6 months of treatment.

Methods: We collected prospective data on pwCF who started ETI and evaluated changes from baseline to 6 months of treatment in pulmonary function (Spirometry and Lung clearance index LCI), nutritional status (BMI), sweat chloride and rate of hospitalization.

Results: Between August 2021 and October 2021, ETI was started in 24 pwCF [12 females, 10 Phe508del-homozygous, median age 20.5 years (range 13-37), all with pancreatic insufficiency]. After 6 months of treatment all respiratory function indicators improved (median changes: +16 ppFEV1, +12 ppFVC, +23 ppFEF 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) (Table1). Over a period of 6-month, only 1 hospitalization due to pulmonary exacerbations was observed as compared to 22 hospitalizations observed in the 6 months before starting ETI (rate per 100 patient-month 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 in headache (n=4), cutaneous rash (n=2), mild haemoptysis (N=2). One pwCF had intestinal subocclusion and required hospitalization. One patient had liver function test elevation after 6 months of therapy during an episode of Sars-Cov2 infection, which required the adjustment of the dose administered.

Conclusions: Our data confirm that ETI treatment is safe, well tolerated and effective in pwCF. ETI improved pulmonary function and nutritional status and remarkably reduced hospitalization rate. Our data indicates that the introduction of ETI in CF care will radically change the natural history and the management approach of the disease

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