P345 The clinical impact of reduced dose prescribing of elexacaftor/tezaxaftor/ivacaftor (ETI) in children with cystic fibrosis

Trikafta® ETI is a triple therapy cystic fibrosis transmembrane conductance regulator (CFTR) medication available in Australia for children over twelve years of age since April 1, 2022. Although it has been found to be a highly effective in the treatment of CF, some individuals require a reduced dose due to drug-drug interactions or significant co-morbidities. To assess the clinical effectiveness of reduced Trikafta® dose regimens, up to 6-months following commencement of therapy, in children attending the CF centre at Sydney Children’s Hospital, Randwick, Australia. A retrospective review of eight patient’s medical records was performed evaluating sweat chloride test levels (ST), lung function and nutritional status before and after commencement of Trikafta®. All clinical measurements were conducted at a time of clinical stability. Children underwent testing prior to commencing Trikafta® (baseline) and at regular intervals up to six months whilst on reduced dose Trikafta® (follow up). Eight patient’s medical records were analysed (4 male) with an age range of 12–17 years. Indication for reduced dose varied; 62.5% were prescribed a reduced dose due to liver impairment, 25% due to mental health concerns and 12.5% for strong CYP3A inhibitor. All patients (100%) had an improvement in ST. 12.5% gained normal ST (<30 mmol/L), 50% of ST were borderline (30–60 mmol/L) and 37.5% had improved from baseline, however remained above 60 mmol/L. Median FEV1 at baseline was 90% (64–99%). At follow up 75% had an improvement in FEV1, of these 50% had a significant improvement (≥ 10%). At baseline 87.5% children had a BMI within the healthy weight range (5th – 85th centile), and at follow up 37% had a BMI above the healthy weight range. This retrospective review of medical records in a small paediatric cohort has demonstrated that a reduced dose of Trikafta® is clinically effective in children where full dose is contraindicated.