Individualized approach to elexacaftor/tezacaftor/ivacaftor dosing in cystic fibrosis, in response to self-reported anxiety and neurocognitive adverse events: A case series

• DOI: 10.3389/fphar.2023.1156621
• Publication Date: 2023-04-27T04:26:04Z
• Authors: Hisham Ibrahim; Hammad Danish; David Morrissey; Kevin F. Deasy; Mairead McCarthy; James Dorgan; Claire Fleming; Ciara Howlett; Sarah Twohig; Tamara Vagg; Desmond M. Murphy; Michael Maher; Barry J. Plant
• Keywords: Ivacaftor; Irritability; Regimen

The prevalence of mental health disorders is high among people with Cystic Fibrosis. psychological symptoms in CF are associated poor adherence, worse treatment outcomes, and greater utilization/cost. Mental neurocognitive Adverse Events (AEs) have been reported all available Fibrosis Transmembrane conductance Regulator (CFTR) modulators small groups patients. We report our experience a dose reduction strategy 10 patients on elexacaftor/tezacaftor/ivacaftor (7.9% total number patients) who self-reported developing intense anxiety, irritability, sleep disturbance and/or slowness after initiation full treatment. Standard resulted 14.3 points improvement mean Percent Predicted Forced Expiratory Volume 1 s (ppFEV1), difference sweat chloride -39.3 mmol/L. initially discontinued reduced therapy according to the AEs severity, subsequent planned escalation every 4-6 weeks guided by sustainability clinical effectiveness, absence recurrence, patients' preferences. Clinical parameters including lung function were monitored for up 12 assess ongoing response regimen. Dose resolution mental/psychological AEs, without loss effectiveness (ppFEV1 was 80.7% standard dose, 83.4% at dose; 33.4 34 mmol/L respectively). Furthermore, subgroup completed 24 regimen, repeat low Computed Tomography imaging showed significant when compared pre-initiation elexacaftor/tezacaftor/ivacaftor.