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

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.

Adverse Effects of Stimulant Interventions for Attention Deficit Hyperactivity Disorder (ADHD): A Comprehensive Systematic Review

“…Finally, the remaining full-text papers were thoroughly reviewed for quality evaluation. The search strategy’s detailed information can be found in Table 1 [ 18 ].…”

“…Subsequently, a quality assessment was performed using specialized instruments for each study type, leading to the inclusion of 13 high-quality studies with a score of over 70%. The final research study consisted of six systematic reviews, five cohort studies, one randomized control trial (RCT), and one traditional review [ 18 ]. Figure 1 displays a flow diagram illustrating the search and selection process.…”

Effects of highly effective modulator therapy on the dynamics of the respiratory mucosal environment and inflammatory response in cystic fibrosis

“…Highly effective modulator therapy with the triple combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (ETI) was approved in 2019 for persons with CF (pwCF) who are ≥12 years of age with ≥1 copy of the F508del variant. 1 Since then, numerous studies have demonstrated significant clinical improvements shortly after initiating treatment with ETI, including enhanced lung function, reduced sweat chloride levels, decreased sputum production, improved infection burden, and improved sinus disease. 2,3 While ETI is revolutionizing the care of pwCF, little is known about its effects on the respiratory mucosa and whether alterations in the host inflammatory response or physiochemical environment may underlie observed clinical improvements.…”

Impact of extended Elexacaftor/Tezacaftor/Ivacaftor therapy on the gut microbiome in cystic fibrosis

“…Following the approval of Elexacaftor/Tezacaftor/Ivacaftor (ETI) triple modulator therapy for pwCF from NHS England, over 60% of all pwCF in the United Kingdom are now registered users [3]. ETI therapy demonstrates increased clinical efficacy as compared to previous dual or mono-therapy approaches [22], yet little information is available on intestinal outcomes and the impact upon the gut microbiota. Given the scarcity of current evidence, the aim of this pilot study was to therefore assess the impact of ETI therapy in pwCF upon the intestinal microbiota.…”