Impact of Elexacaftor-Tezacaftor-Ivacaftor on Quality of Life in Children With Cystic Fibrosis.

OBJECTIVES: CFTR modulators have revolutionized cystic fibrosis (CF) management by targeting the defective protein rather than its consequences. Their impact on quality of life (QoL) have been studied in numerous trials, but few data are available on QoL in patients receiving Elexacaftor-Tezacaftor-Ivacaftor (ETI), notably in children given its recent authorization for this age group. We aimed to assess the impact of ETI on children's QoL.

METHODS: This prospective observational study included children with CF (6-17 years), assessing QoL using the CF Questionnaire Revised (CFQ-R) before (baseline) and 3 months after (M3) starting ETI treatment for children and their caregivers.

RESULTS: We included 23 children (median [range]) age 10.2 [6-17.2] years, 13 (57%) with homozygous F508del genotype. The total QoL score at baseline ([mean (SD)] children: 74.07 [10.86]; caregivers: 73.21 [10.38]) reflected severe disease impact, particularly regarding treatment burden in the children's perspective (63.28 [21.04]) and digestive domains in the caregivers' perspective (digestive symptoms: 66.67 [17.37]; eating disorder: 67.54 [32.14]; weight: 61.40 [33.82]). At M3, there was a significant increase in reported QoL (p = 0.0001), particularly regarding physical domains. Emotional/social/school domains barely showed improvement. Although QoL mean scores were comparable between children and caregivers' groups, they were poorly correlated within the same family. Homozygous F508del genotype was associated with better QoL improvement at M3 compared to composite heterozygous genotypes (p < 0.001).

CONCLUSION: ETI treatment has a significant impact on children's QoL, particularly in physical health domains. Other QoL domains that are not improved by ETI need to be addressed, in particular, psycho-social components. Both children's and caregivers' perspectives must be considered for a holistic picture of children's QoL.