Introduction: In clinical trials, Elexacaftor/Tezacaftor/Ivacaftor (ETI) showed effectivity and good tolerability. However, real-life experience suggests this drug might be associated with a wider range of adverse effects (AE) than previously thought, namely neuropsychiatric (NPAE). 

Aims and Objectives: We aimed to assess the AE experienced by patients (pts) on ETI, in a real-life setting.

Methods: We performed a retrospective study of the pts on ETI followed at a Portuguese Cystic Fibrosis Centre from March 2021 to January 2023. Data on AE up to one year after ETI start was collected.

Results: Forty-five pts were started on ETI. Eleven (24%) presented skin rash. Four (9%) reported testicular hypersensitivity. Fifteen (33%) had gastrointestinal symptoms. Eleven pts presented self-limited changes of liver function tests and 6 (13%) of creatine kinase. Two pts reported haemoptysis. Five (11%) developed arterial hypertension and 7 (16%) dyslipidaemia. Twenty-four (53%) presented NPAE, namely headache (36%), vision (2%), hearing (2%) and speech disturbances (4%), memory changes (9%), low mood (13%), insomnia (4%), irritability (7%) and anxiety (11%). One patient was diagnosed with bipolar disorder. Treatment was permanently suspended in one patient with memory and concentration problems and temporarily suspended in one with persistent headache. Dose was adjusted in a patient with persistent irritability and low mood. Two pts died while on ETI. One, with a previously undiagnosed Chiari malformation, died from intracranial hypertension and another from aortic dissection.

Conclusions: We found a high incidence of neuropsychiatric AE. While most were mild, drug suspension or dose reduction were required in a few cases.