Dose adjustments of Elexacaftor/Tezacaftor/Ivacaftor in response to mental health side effects in adults with cystic fibrosis.

Introduction: Deterioration in mental health has been reported in a minority of individuals with cystic fibrosis starting elexacafor/tezacaftor/ivacaftor (ELX/TEZ/IVA). We report our experience of using sweat chloride and markers of clinical stability to titrate dose reduction with the aim of minimising adverse events and maintaining clinical stability.
Method: Adults (n = 266) prescribed ELX/TEZ/IVA, were included. Adverse events, sweat chloride, lung function and clinical data were collected.
Results: Nineteen (7.1%) individuals reported anxiety, low mood, insomnia and "brain fog" with reduced attention and concentration span. Thirteen underwent dose reduction with sweat chloride remained normal (<30 mmol l-1) or borderline (30-60 mmol l-1) in six (46.2%) and seven (53.2%) cases respectively. Improvement or resolution of AEs occurring in 10 of the 13 cases.
Conclusion: Dose adjustment of ELX/TEZ/IVA was associated with improvement in mental health AEs without significant clinical deterioration. Sweat chloride concentration may prove useful as a surrogate marker of CFTR function.
Competing Interests: Declaration of Competing Interest D Peckham reports past educational speaker and advisory board fees from Vertex. N Shaw reports speaker fees for educational talks from Vertex.
(Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)