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Observational Study
. 2025 Jan 17;15(1):2247.
doi: 10.1038/s41598-025-86010-1.

Body composition changes and clinical outcomes in pediatric cystic fibrosis during 24 months of lumacaftor ivacaftor therapy based on real-world data

Marcell Imrei  1   2 , Adrienn F Kéri  1 , Éva Gács  1 , Ildikó Gönczi  1 , Melinda Meláth  1 , Éva Kosaras  3 , Botond Demeter  3 , Csaba Péterfia  4 , Klára Vass  5 , Gyöngyi Székely  6 , Klementina Ocskay  1   7 , Andrea Párniczky  8   9   10
Affiliations
Observational Study

Body composition changes and clinical outcomes in pediatric cystic fibrosis during 24 months of lumacaftor ivacaftor therapy based on real-world data

Marcell Imrei et al. Sci Rep. .

Abstract

Clinical trials demonstrate the short-term efficacy of dual CFTR modulators, but long-term real-world data is limited. We aimed to investigate the effects of 24-month lumacaftor/ivacaftor (LUM/IVA) therapy in pediatric CF patients (pwCF). This observational study included pwCF homozygous for F508del mutation treated between 2021 and 2023. We report data for the first 24 months from therapy initiation. Variables were analyzed separately for ages 2-5, 6-11, and over 12. Data from 49 pwCF (median age: 9.3 years (5.5-14.2)) showed that ppFEV1 values after a transient increase at 12 months, decreased from 102% (82-114) at baseline to 87% (74-96) at 24 months. The decrease was more pronounced with higher initial ppFEV1. Median sweat chloride concentration decreased from 75 mmol/L (69-82) to 57 mmol/L (43-70) without any association with respiratory function change. Median BMI z-score increased from - 0.81 (- 1.37-0.49) to - 0.39 (- 0.88 to - 0.04) (p = 0.288), and the proportion of underweight and overweight children decreased. Skeletal muscle mass remained stable, while fat mass significantly increased (p = 0.011). Fecal elastase levels improved, especially among younger patients. These findings underscore the potential benefits of early initiation of CFTR modulator therapy in pediatric CF patients, highlighting improvements in nutritional status and pancreatic function.

Keywords: Body composition; CFTR modulator therapy; Fecal elastase; LUM/IVA; Normal-weight obesity; Pancreatic function.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The highest annual ppFEV1 values in the three years prior to therapy initiation and during the first and second years of LUM/IVA therapy. Solid blue line represents the median value, dashed lines represent the 1st and 3rd quartiles (ppFEV1: percentile predicted forced expiratory volume in the first second).
Fig. 2
Fig. 2
(a) Association between the initial ppFEV1 and the ppFEV1 after 24 months of LUM/IVA therapy (b) Association between the initial sweat chloride concentration and levels after 24 months of LUM/IVA therapy (c) Association between the change of ppFEV1 and the change of sweat chloride concentration during the 24-month LUM/IVA therapy. Dotted lines represent the trend lines, arrows represent the greater reduction at higher initial values. (LUM/IVA: lumacaftor/ivacaftor; ppFEV1: percentile predicted forced expiratory volume in the first second).
Fig. 3
Fig. 3
Distribution of participants by (a) BMI percentile and (b) BMI categories at the initiation of LUM/IVA therapy and at 24 months (LUM/IVA: lumacaftor/ivacaftor).
See this image and copyright information in PMC

References

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