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Review
. 2022 Sep 20;14(9):e29359.
doi: 10.7759/cureus.29359. eCollection 2022 Sep.

Newly Discovered Cutting-Edge Triple Combination Cystic Fibrosis Therapy: A Systematic Review

Sarah N Dawood  1 , Ahmad M Rabih  2 , Ahmad Niaj  2 , Aishwarya Raman  2 , Manish Uprety  2 , Maria Jose Calero  3 , Maria Resah B Villanueva  4 , Narges Joshaghani  5 , Nicole Villa  2 , Omar Badla  6 , Raman Goit  2 , Samia E Saddik  2 , Lubna Mohammed  2
Affiliations
Review

Newly Discovered Cutting-Edge Triple Combination Cystic Fibrosis Therapy: A Systematic Review

Sarah N Dawood et al. Cureus. .

Abstract

A cystic fibrosis (CF) transmembrane conductor regulator (CFTR) gene modulating triple therapy combining elexacaftor-tezacaftor-ivacaftor (Trikafta) has been recently discovered. Its approval by the Food and Drug Administration (FDA) in 2019 has expanded the target therapy group to individuals aged twelve and up with at least one Phe508del (phenylalanine 508 deletion) mutation in the CFTR gene. This systematic review aims to assess this combination therapy's safety and efficacy. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, an in-depth search was performed. The search was done by utilizing databases such as PubMed Central (PMC), Google Scholar, and Science Direct for articles related to this topic. Studies published in the last five years in the English language were chosen preliminarily. Further eligibility criteria and quality assessment tools were employed to assess the risk of bias and finalize ten articles to be used in this review. The chosen articles constituted four randomized control trials (RCTs), four systematic reviews, and two narrative reviews. The last date for data collection was April 24, 2022. Based on the findings of this review, we concluded that by combining three CFTR modulators, this therapy had outperformed all the currently available medications in terms of improving pulmonary function, reducing exacerbations, and enhancing the quality of life of CF patients. In clinical trials, headache and rash were the most common side effects, and laboratory testing to assess liver function is suggested. Long-term safety and effectiveness must be confirmed by the continued review of real-life patient data. Studies done on triple therapy thus far have been promising. Unfortunately, a small proportion of the CF population remains ineligible for any form of CFTR modulator therapy owing to their type of genetic mutation, and this provides ground for further research in this field.

Keywords: cftr gene mutation; cftr modulating therapy; cftr modulator; cystic fibrosis (cf); cystic fibrosis triple therapy; elexacaftor; ivacaftor; phe508 mutation; tezacaftor; trikafta.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Prevalence of having at least one mutation from each class among cystic fibrosis patients
Figure 2
Figure 2. Prisma flow chart.
Assessment of multiple systematic reviews 2 (AMSTAR 2); Scale for the assessment of narrative review articles 2 (SANRA 2); Cochrane collaboration risk of bias tool (CCRBT).
See this image and copyright information in PMC

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References

    1. A review of Trikafta: triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Zaher A, ElSaygh J, Elsori D, ElSaygh H, Sanni A. Cureus. 2021;13:0. - PMC - PubMed
    1. Clinical development of triple-combination CFTR modulators for cystic fibrosis patients with one or two F508del alleles. Taylor-Cousar JL, Mall MA, Ramsey BW, et al. ERJ Open Res. 2019;5:82–2019. - PMC - PubMed
    1. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Heijerman HG, McKone EF, Downey DG, et al. Lancet. 2019;394:1940–1948. - PMC - PubMed
    1. Progress in precision medicine in cystic fibrosis: a focus on CFTR modulator therapy. Tewkesbury DH, Robey RC, Barry PJ. Breathe (Sheff) 2021;17:210112. - PMC - PubMed
    1. Elexacaftor-tezacaftor-ivacaftor: the first triple-combination cystic fibrosis transmembrane conductance regulator modulating therapy. Ridley K, Condren M. J Pediatr Pharmacol Ther. 2020;25:192–197. - PMC - PubMed

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