Changes in Neuropsychiatric Symptoms after Switching from Elexacaftor/Tezacaftor/Ivacaftor to Vanzacaftor/Tezacaftor/Deutivacaftor: A Single-Center Experience.

Authors

Julie Galipean, Denis Hadjiliadis, Samantha Kane, William Longacre, Gina Hong

Published in

Respiratory medicine. Pages 109268. Nov 06, 2026. Epub Nov 06, 2026.

Abstract

Neuropsychiatric adverse effects (AEs) have increasingly been reported with elexacaftor/tezacaftor/ivacaftor (ETI) in people with cystic fibrosis (PwCF). Vanzacaftor/tezacaftor/deutivacaftor (VTD) demonstrated similar rates of neuropsychiatric events to ETI in clinical trials; however, individuals with prior ETI intolerance were not specifically studied. We evaluated neuropsychiatric outcomes after switching from ETI to VTD in PwCF with documented ETI-related neuropsychiatric AEs.
We performed a retrospective chart review of adults with cystic fibrosis with documented ETI-related neuropsychiatric AEs who transitioned to VTD and had at least one follow-up visit. Patient-reported symptom changes, Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scores were assessed before and after VTD initiation. Changes in screening scores were analyzed using Wilcoxon signed-rank test. Agreement between patient-reported improvement and clinically meaningful reductions in GAD-7 and PHQ-9 scores was evaluated using Cohen's kappa.
Twenty-three patients were included (median age 40 years, 60.9% female). Nineteen (82.6%) reported improvement in neuropsychiatric symptoms after transitioning to VTD. GAD-7 scores improved significantly (median 6 [IQR: 2 -10] vs. 3 [IQR: 0-7], p=0.005), while PHQ-9 scores decreased from a median of 6 [IQR: 2-9] to 3 [IQR: 2-8], p=0.05. Agreement between patient-reported improvement and clinically meaningful changes in GAD-7 (κ = -0.107, 95% CI [-0.351, 0.136], p=0.81) and PHQ-9 (κ = 0.123, 95% CI [0.077, 0.323], p=0.12), was poor to slight.
Most PwCF with ETI-related neuropsychiatric AEs reported improvement after switching to VTD. Standard anxiety and depression screening tools may not fully capture CFTR modulator-associated neuropsychiatric symptoms. Larger prospective studies are needed.

PMID:
42994765
Bibliographic data and abstract were imported from PubMed on 07 Nov 2026.

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