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Current Reviews in Clinical and Experimental Pharmacology


ISSN (Print): 2772-4328
ISSN (Online): 2772-4336


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

Author(s): Alaa Hassan Yousif Hamdan, Faiza Zakaria, Maria Kezia Lourdes Pormento, Odunayo Susan Lawal, Adaugo Opiegbe, Samina Zahid, Prathima Guntipalli, Ujala Nasr and Syed Asad Hasan Rizvi*

Volume 19, Issue 1, 2024

Published on: 24 February, 2023

Page: [93 - 110] Pages: 18

DOI: 10.2174/2772432818666230201094115

Price: $65


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, 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.

Keywords: Cystic fibrosis, CFTR protein modulators, elexacaftor, ivacaftor, tezacaftor, meta-analysis, conductance.

Graphical Abstract
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