Baseline results from the NEMO study: psychometric evaluation of the preschool cystic fibrosis questionnaire-revised in children with cystic fibrosis and caregivers in the United States and Australia

Abstract

Background: The Cystic Fibrosis Questionnaire-Revised (CFQ-R) is a widely used, validated instrument to assess health-related quality of life (HRQOL) for ages 6+. The ongoing NEMO Study is a prospective, multicenter, non-interventional study designed to psychometrically evaluate the preschoolage version of the CFQ-R (Preschool CFQ-R: Preschool Pictorial CFQ-R [child report for ages 3–5 years]; Preschool CFQ-R [caregiver proxy for caregivers with children aged 2–5 years]) and assess the impact of ELX/TEZ/IVA initiation on clinical outcomes, patient-reported outcomes, and caregiverreported outcomes. In this interim analysis, we evaluate baseline data to: (1) assess the ability of children with cystic fibrosis (CF) aged 3–5 years to complete the Preschool Pictorial CFQ-R; and (2) among those who initiated ELX/TEZ/IVA, understand how children rate the Preschool Pictorial CFQ-R domains prior to initiation. Methods: This interim analysis includes 217 participants (75 children with CF aged 3–5 years, 142 caregivers of children with CF aged 2–5 years) across 32 sites in the United States and Australia who initiated ELX/TEZ/IVA between March 2023-November 2024 and completed the Preschool CFQ-R at baseline (prior to ELX/TEZ/IVA initiation). Children and their caregivers were enrolled together (dyads) or separately (non-dyads). Data included extraction of retrospective electronic medical record data for 12 months prior to and prospective data collection during clinic visits up to 12 months after ELX/TEZ/IVA initiation. An interviewer administered the 29-item Preschool Pictorial CFQ-R to the child in clinic. A positive reinforcement system (animal puzzle images) was integrated into the Preschool Pictorial CFQ-R to encourage participation and keep the child's attention. Caregivers completed the 44-item Preschool CFQ-R caregiver proxy using a link. Demographics, clinical characteristics, and CFQ-R domains were evaluated at baseline. Domain scores ranged from 0 to 100, with higher scores indicating better HRQOL. Results: Most (83.8%, 217/259) of the enrolled study participants initiated ELX/TEZ/IVA and completed the Preschool CFQ-R. Among ELX/TEZ/IVA initiators, 52.0% (39/75) of children and 85.9% (122/142) of caregivers were female. The mean (SD) age at enrollment for children and caregivers was 4.4 (0.8) years and 34.3 (5.8) years, respectively. Mean (SD) BMI-for-age percentile of children at baseline was 62.1 (28.1), 49.3% (37/75) had previous CFTR modulators use, and 76.0% (57/75) used pancreatic enzyme replacement therapy. 49.2% (29/59) of those reporting pulmonary exacerbations (PEx) had ≥ 1 PEx in the preceding 12 months before ELX/TEZ/IVA initiation. About 88.0% (66/75) of children aged 3–5 years completed the minimum number of items for scoring the Preschool CFQ-R domains. In general, median scores were lower among children than those reported by caregivers (Table 1). All Preschool Pictorial CFQ-R domains have median scores of < 85, with the lowest scores reported for the Treatment Burden, Emotional Functioning, Respiratory Symptoms, and Digestive Functioning domains. Conclusions: Most children were able to complete the Preschool Pictorial CFQ-R. Median scores of <85 in all domains show unmet need and the opportunity to demonstrate benefit from ELX/TEZ/IVA treatment using the Preschool CFQ-R. Further research is underway to complete the full psychometric validation of the Preschool CFQ-R and compare the concordance between child-caregiver dyads. Acknowledgements: Vertex Pharmaceuticals Inc.