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.

Probing Phosphorylation-Induced Vibrational Couplings in CFTR by 2D IR Spectra Simulations

“…CFTR is a chloride channel residing in epithelial tissues, orchestrates the vital secretory functions of various organs and tissues. It governs the flow of ions and water onto the apical surface of epithelia lining our airways, sweat glands, and exocrine organ lumens (1, 2). Malfunctioning or down regulation of CFTR channels trap chloride ions within cells, preventing the crucial hydration of cellular surfaces.…”