Cystic Fibrosis Transmembrane Conductance Regulator Protein Modulators in Children and Adolescents with different CF Genotypes - Systematic Review and Meta-Analysis.

Abstract

Objective: To determine the efficacy of the first triple CFTR protein modulators in children and adolescents with cystic fibrosis.

Methods: Systematic review and meta-analysis were conducted, following PRISMA guidelines. The following databases were searched extensively: PubMed/Medline, Clinical trials.gov, Google Scholar, Scopus, Embase, and Europe PMC using the keywords: "Ivacaftor," "Elexacaftor," "Tezacaftor," VX_661", VX_770", "VX_445", "cystic fibrosis". A total of ten randomized clinical trials were included in our analysis. Primary outcomes included: Absolute change in predicted FEV1 from baseline, Absolute change in sweat chloride test from baseline, Absolute change in BMI from baseline, Absolute change in CF-QR from baseline, and Adverse Events.

Results: Among primary findings, significant absolute change in predictive FEV1 from baseline through 4 weeks favoured the triple CFTR protein modulators. [MD=11.80,95%CI=8.47_15.12, p value=<0.00001]; as well as CF_QR score [MD=0.00,95%CI=-2.50_2.50, p value=1.00], and BMI kg/m² change [MD=16.90,95%CI=12.73_21.06, p value=<0.00001]. No significant change was noted for CFTR channels activity in the treatment group when compared to placebo or VX_770/VX_661 [MD= -12.57,95%CI=-94.46_69.32, p value=0.76].

Conclusion: In children aged ≥ 6 y old and adolescents with F508del_CFTR mutation, Elexacaftor-Tezacaftor-Ivacaftor tend to be more effective than first-generation therapy, demonstrating promising results by exhibiting significant improvement in lung function, body weight, and respiratory-related quality of life.