Effectiveness of lumacaftor/ivacaftor initiation in children with cystic fibrosis aged 2 through 5 years on disease progression: Interim results from an ongoing registry-based study

Claire Kim; Mark Higgins; Lingyun Liu; Nataliya Volkova; Anna Zolin; Lutz Naehrlich; ECFSPR Study Group

doi:10.1016/j.jcf.2024.02.004

Effectiveness of lumacaftor/ivacaftor initiation in children with cystic fibrosis aged 2 through 5 years on disease progression: Interim results from an ongoing registry-based study

J Cyst Fibros. 2024 Feb 23:S1569-1993(24)00017-1. doi: 10.1016/j.jcf.2024.02.004. Online ahead of print.

Authors

Claire Kim¹, Mark Higgins², Lingyun Liu², Nataliya Volkova², Anna Zolin³, Lutz Naehrlich⁴; ECFSPR Study Group

Affiliations

¹ Vertex Pharmaceuticals Incorporated, Boston, MA, USA. Electronic address: Claire_Kim@vrtx.com.
² Vertex Pharmaceuticals Incorporated, Boston, MA, USA.
³ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
⁴ Department of Pediatrics, Justus-Liebig-University Giessen, Giessen, Germany.

PMID: 38402082
DOI: 10.1016/j.jcf.2024.02.004

Abstract

Background: Lumacaftor/ivacaftor (LUM/IVA) has been shown to be safe and efficacious in people with cystic fibrosis (CF) ≥1 year of age. To assess the impact of early LUM/IVA initiation on CF disease progression, a 6-year observational study leveraging data from existing CF patient registries is being conducted in children with CF homozygous for F508del (F/F genotype) who were aged 2 through 5 years at treatment initiation. Here we present interim results from this study focusing on data from the European CF Society Patient Registry (ECFSPR).

Methods: The LUM/IVA cohort included children in the ECFSPR who started LUM/IVA between 15 January 2019 and 31 December 2020. Longitudinal trends in growth parameters, pulmonary exacerbations, hospitalizations, safety outcomes, and other effectiveness outcomes in the LUM/IVA cohort were compared to those in two modulator-naïve cohorts: (i) matched concurrent cohort heterozygous for F508del and a minimal function mutation (F/MF concurrent comparator cohort) and (ii) matched concurrent cohort with the F/F genotype from countries without commercial access to LUM/IVA as of 2020 (F/F concurrent comparator cohort).

Results: The LUM/IVA cohort matched to the F/MF concurrent comparator cohort had 681 children and the LUM/IVA cohort matched to the F/F concurrent comparator cohort had 183 children. LUM/IVA cohorts had increases in body mass index percentiles relative to the matched F/MF and F/F concurrent comparator cohorts (mean difference in change from baseline: 8.4 [95% CI: 5.5, 11.3] and 11.8 [95% CI: 5.9, 17.7], respectively). Increases in height and weight percentiles were also observed in the LUM/IVA cohort relative to the F/MF and F/F concurrent comparator cohorts. Reductions in pulmonary exacerbations and hospitalizations relative to baseline and the F/F concurrent comparator cohort were seen in 2021.

Conclusions: This interim analysis showed favorable trends in clinical outcomes, including growth parameters, pulmonary exacerbations, and hospitalizations, suggesting an early beneficial effect of LUM/IVA treatment in children aged 2 through 5 years at treatment initiation.

Keywords: CFTR modulators; CFTR therapies; Children; Cystic fibrosis; Ivacaftor; Lumacaftor.