Clinical efficacy of elexacaftor-tezacaftor-ivacaftor in two siblings with homozygous I1234V mutation cystic fibrosis: A prospective case series.

Background: The missense CFTR variant I1234V (c.3700A > G) produces class II protein-folding defects and is prevalent in the Middle East, yet clinical evidence for elexacaftor/tezacaftor/ivacaftor (ETI) in homozygous carriers is sparse. We prospectively evaluated ETI efficacy and safety in two paediatric siblings with homozygous I1234V cystic fibrosis (CF). Methods: A single-centre, prospective case series was undertaken at King Fahad Medical City. Baseline assessments included spirometry, body-mass index (BMI), sputum microbiology, liver biochemistry and high-resolution chest CT. ETI was initiated according to weight-based dosing and patients were reviewed at 6 and 8 months. Primary outcomes were change in percent-predicted forced expiratory volume in 1 second (ppFEV Results: After eight months of ETI, ppFEV Conclusions: ETI produced clinically meaningful improvements in lung function, nutritional status, microbiological clearance and radiological appearance in two children homozygous for the rare I1234V mutation. These real-world findings support extending ETI access to patients with rare class II CFTR variants and justify larger multicentre studies to confirm efficacy and long-term safety.