Clinical and biochemical response to elexacaftor/tezacaftor/ivacaftor in a patient with the rare L927P/N1303K CFTR genotype.

Elexacaftor/tezacaftor/ivacaftor (ETI) has transformed the treatment of cystic fibrosis (CF), although evidence in individuals carrying rare CFTR variants remains limited. We report the clinical and biochemical response to ETI in a 25-year-old woman with advanced CF carrying the rare L927P/N1303K genotype. Following initiation of ETI under specialist supervision, the patient experienced marked improvement in respiratory symptoms, exercise tolerance, nutritional status, and oxygen requirements. Six pulmonary exacerbations requiring hospitalisation and intravenous antibiotics occurred during the two years preceding full-dose ETI therapy, compared with none during the subsequent 18-month follow-up. Overnight enteral feeding was discontinued, body weight increased, and sweat chloride concentration decreased from 95 to 75 mmol/L, with sustained improvement thereafter. Lung function remained stable despite severe baseline airflow obstruction. This case adds to the growing evidence supporting ETI responsiveness in N1303K-associated disease and contributes further clinical experience in the rare L927P/N1303K genotype. It also highlights the importance of integrating clinical outcomes with theratyping when considering treatment for individuals carrying rare CFTR variants.