Triple combination cystic fibrosis transmembrane conductance regulator modulator therapy in the real world – opportunities and challenges

Barry, Peter J.; Taylor‐Cousar, Jennifer L.

doi:10.1097/mcp.0000000000000819

Cited by 21 publications

(21 citation statements)

References 55 publications

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“…Elexacaftor is a CFTR corrector that operates at a different binding location on the CFTR protein than tezacaftor to improve the CFTR protein's functioning at the cell surface [ 15 ]. When administered as a combination, Trikafta enhances the function of the Phe508del mutant CFTR protein on the cell surface, resulting in greater chloride ion transport and amelioration of symptoms [ 9 , 16 , 17 ].…”

Section: Reviewmentioning

confidence: 99%

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

Dawood¹,

Rabih²,

Niaj³

et al. 2022

Cureus

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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.

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Section: Reviewmentioning

confidence: 99%

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

Dawood¹,

Rabih²,

Niaj³

et al. 2022

Cureus

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“…Because of their rare mutations, Black, Indigenous, and People of Color (BIPOC) are overrepresented in this group of pwCF 10 . Additionally, there are pwCF who do not tolerate CFTR modulators because of side effects 11 . Finally, while all four drugs have approval in the United States with broad in vitro based application, approval varies widely by nation, with some nations having no access to CFTR modulators 11 .…”

Section: Introductionmentioning

confidence: 99%

“…10 Additionally, there are pwCF who do not tolerate CFTR modulators because of side effects. 11 Finally, while all four drugs have approval in the United States with broad in vitro based application, approval varies widely by nation, with some nations having no access to CFTR modulators. 11 Although registries can be utilized to describe clinical characteristics of those not eligible for modulators in one region or country, registries do not capture the burden of care individuals in that group or their family members live with on a day-to-day basis nor their perceptions about participating in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

A survey: Understanding the health and perspectives of people with CF not benefiting from CFTR modulators

Kramer-Golinkoff¹,

Camacho²,

Kramer³

et al. 2022

Pediatric Pulmonology

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Background: While the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulator use has improved daily life and long-term prognosis of CF for many with approved CFTR mutations, approximately 10% of people with CF (pwCF) have only symptomatic treatments available. Methods: Between June 10 and July 1, 2021, Emily's Entourage distributed a 38question anonymous survey targeted at pwCF not benefitting from approved modulators via social media and email to pwCF and CF advocacy groups in and outside the United States regarding health status, impact of CF, unmet needs, and clinical research interest.Results: There were 431 survey respondents representing pwCF on five continents.The majority of pwCF had moderate lung disease (50.3%). Ineligibility based on CFTR mutation (64.1%) was the most frequently reported reason pwCF were not on modulators. PwCF reported the most impacted aspects of life were mental (66.7%) and physical (40.7%) health. Financial concerns and feelings of isolation were commonly reported. Witnessing improvements for peers with access to modulators was both uplifting and disheartening. The majority of pwCF would be interested in participating in future clinical research (77.6%), although some living outside of the United States cited lack of opportunity to participate in clinical trials as a barrier.Conclusions: PwCF who are ineligible, intolerant, or lack access to modulators have a high burden of disease impacting their physical and mental health. Although most are happy for those who are benefiting from modulators, they are eager for the opportunity to experience similar improvements for themselves, and willing to participate in clinical trials of new therapies.

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“…LUM/IVA and TEZ/IVA were the first FDA-approved combination therapies for pwCF carrying the F508del gene defect. The results obtained with these combinations were very promising [4], but the combination of TEZ/IVA with the next-generation corrector ELX produces significant, sustained effects in pwCF homozygous and heterozygous for F508del, including improved percent predicted forced expiratory volume in 1 s (ppFEV 1 ) and body mass index (BMI), decreased pulmonary exacerbation rate, and improved quality of life [5]. This highlights the potential of this new, highly effective CFTR modulator therapy.…”

Section: Introductionmentioning

confidence: 99%

Effect of Triple Combination CFTR Modulator Therapy on Sleep in Adult Patients with Cystic Fibrosis

et al. 2022

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Background: Sleep-disordered breathing (SDB) and disturbed sleep are common, often underrecognized, comorbidities in people with cystic fibrosis (pwCF). Objectives: We studied the effect of CFTR triple combination therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on sleep in pwCF. Method: This was a prospective, observational sleep study in clinically stable adult pwCF. All participants underwent overnight polysomnography (PSG), before (T0) and after (T1) initiation of CFTR modulator therapy with ELX/TEZ/IVA. In addition, pulmonary function tests, calculation of BMI, and sweat chloride testing were performed. Results: Twenty-nine pwCF (mean age 32 ± 8 years; 15 female) participated in the study. Mean time between T0 and T1 was 194 ± 21 days. Total sleep time (TST) was 298 ± 40 min, with decreased sleep efficiency (SE) (76 ± 109) and increased sleep latency (SL) (73 ± 38 min). Sleep stages for NREM (N1–3) and REM sleep were within the normal range. Nocturnal respiratory events mainly occur during REM sleep (T0: AHI REM 8.3 ± 9.0/h; ODI REM 9.4 ± 10.6/h), whereas the overall AHI was normal (3.6 ± 3.7/h). After initiation of ELX/TEZ/IVA, we saw significant improvements in ppFEV1 (p < 0.001) and BMI (p < 0.001) and a reduction in sweat chloride levels (p < 0.001). In parallel, there was a reduction in AHI (p = 0.003), ODI (p = 0.001), and nocturnal respiratory rate (p < 0.001), both in total, REM and NREM sleep. Neither TST, SL, SE, nor sleep architecture was influenced (all p > 0.05). Conclusions: Initiation of ELX/TEZ/IVA resulted in significant improvements in SDB in adult pwCF.

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Triple combination cystic fibrosis transmembrane conductance regulator modulator therapy in the real world – opportunities and challenges

Cited by 21 publications

References 55 publications

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

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

A survey: Understanding the health and perspectives of people with CF not benefiting from CFTR modulators

Effect of Triple Combination CFTR Modulator Therapy on Sleep in Adult Patients with Cystic Fibrosis

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