NEUROPSYCHIATRIC SYMPTOMS 6-MONTHS POST ELEXACAFTOR/TEZACAFTOR/IVACAFTOR INITIATION IN CHILDREN

Abstract

Introduction/Aim: Elexacaftor/tezacaftor/ivacaftor (ETI) significantly improves clinical outcomes and quality of life in many people with Cystic Fibrosis (CF). While generally well tolerated, adverse mental health and sleep outcomes are reported in adolescent and adult populations within the first 3-months of ETI treatment, raising concerns about potential neuropsychiatric side effects in children. This study aims to evaluate the impact of ETI on these outcomes in children aged 6-11 years. Methods: 108 children aged 6-11yrs were recruited from the CF Clinic at Queensland Children's Hospital. Neuropsychiatric outcomes were measured using parent-reported questionnaires: Paediatric Symptom Checklist (PSC), Sleep Disturbance Scale for Children (SDSC) before commencing ETI (baseline), +1-month and +6-months after ETI initiation. Scores were categorised as normal or clinically significant using established thresholds. Results: 66 (61%) caregivers completed the PSC and SDSC at all timepoints: clinically significant scores for PSC were observed in 20% at baseline, 12% at +1-month, and 18% at +6-months, and for SDSC in 17%, 15%, and 9%, respectively. PSC and SDSC categorisation over time is summarised in table 1. For each questionnaire 4 (6%) remained clinically significant throughout. 10 (15%) became clinically significant at any timepoint for PSC and/or SDSC post ETI, but of the children that moved from normal to clinically significant at +1-month (6, 9%) all returned to normal at +6-month. Conclusion: Most (>70%) children in our cohort did not experience any changes in score classification for either mental health or sleep disturbance during the first 6-months of ETI therapy. Deterioration in scores from baseline-normal to clinically significant at +1-month experienced by 9% children appeared transient with all returning to normal scores by +6-months. Ongoing follow-up will characterise changes in mental health and sleep over the first 12-months of ETI use.