Trikafta and Psychopathology in Cystic Fibrosis: A Case Report

Tindell, William; Su, Amanda; Oros, Sarah M.; Rayapati, Abner O.; Rakesh, Gopalkumar

doi:10.1016/j.psym.2020.06.021

Cited by 33 publications

(39 citation statements)

References 12 publications

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“…ELX/TEZ/IVA was also associated with mental health-related AE, as described in a case report of a 19-year-old female [54]. In the described case, the patient experienced worsening of baseline depression and sleep paralysis with hypnopompic hallucinations, and new passive suicidal ideation following initiation of ELX/TEZ/IVA [54]. The latter resolved upon discontinuation, but initiation of an antidepressant was necessary to improve mood [54].…”

Section: Elexacaftor/tezacaftor/ivacaftor (Elx/tez/iva)mentioning

confidence: 69%

“…In the described case, the patient experienced worsening of baseline depression and sleep paralysis with hypnopompic hallucinations, and new passive suicidal ideation following initiation of ELX/TEZ/IVA [54]. The latter resolved upon discontinuation, but initiation of an antidepressant was necessary to improve mood [54]. Over the course of several months, the ELX/TEZ/IVA dose was titrated, and dosage times changed in response to worsening mood, suicidality, anxiety, and sleep paralysis.…”

Section: Elexacaftor/tezacaftor/ivacaftor (Elx/tez/iva)mentioning

confidence: 94%

“…Fourteen (26%) of the observational studies focused on patients with severe airflow obstruction, defined as ppFEV 1 < 40%; in 11 of these studies, patients accessed the CFTR modulator via a compassionate access program (also referred to as a "managed access", "early access', "expanded access", or "named patient" program) through the manufacturer [25,26,[29][30][31][32][33][34][35][36][37][38][39][40]. Twenty (65%) of the full manuscripts were deemed to have safety as a primary focus or outcome [27][28][29][30]32,33,[41][42][43][44][45][46][47][48][49][50][51][52][53][54].…”

Section: Description Of Studiesmentioning

confidence: 99%

See 2 more Smart Citations

Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review

Dagenais

Quon

2020

JCM

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Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies target the underlying cause of cystic fibrosis (CF), and are generally well-tolerated; however, real-world studies indicate the frequency of discontinuation and adverse events (AEs) may be higher than what was observed in clinical trials. The objectives of this systematic review were to summarize real-world AEs reported for market-available CFTR modulators (i.e., ivacaftor (IVA), lumacaftor/ivacaftor (LUM/IVA), tezacaftor/ivacaftor (TEZ/IVA), and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA)), and to identify ways in which the pharmacist on CF healthcare teams may contribute to mitigating and managing these AEs. The MEDLINE, EMBASE, CINAHL, and Web of Science Core Collection online databases were searched from 2012 to 1 Aug 2020. Full manuscripts or conference abstracts of observational studies, case series, and case reports were eligible for inclusion. The included full manuscripts and conference abstracts comprised of 54 observational studies, 5 case series, and 9 case reports. The types of AEs reported generally aligned with what have been observed in clinical trials. LUM/IVA was associated with a higher frequency of respiratory-related AE and discontinuation in real-world studies. A signal for mental health and neurocognitive AEs was identified with all 4 CFTR modulators. A systematic approach to monitoring for AEs in people with CF on CFTR modulators in the real-world setting is necessary to help better understand potential AEs, as well as patient characteristics that may be associated with higher risk of certain AEs. Pharmacists play a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies.

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Section: Elexacaftor/tezacaftor/ivacaftor (Elx/tez/iva)mentioning

confidence: 69%

Section: Elexacaftor/tezacaftor/ivacaftor (Elx/tez/iva)mentioning

confidence: 94%

Section: Description Of Studiesmentioning

confidence: 99%

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Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review

Dagenais

Quon

2020

JCM

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“…A new combination tablet composed of elexacaftor (vx-445), tezacaftor, and ivacaftor was FDA approved in 2019 for the treatment of CF patients 6years of age and older who carry at least one F508del mutation (Trikafta, Vertex Pharmaceuticals, Boston, MA, USA) [ 37 , 38 , 39 , 40 ]. It is recommended that one tablet containing 100 mg elexacaftor, 50 mg tezacaftor, and one tablet containing only 75 mg ivacaftor be taken in the morning, followed by taking an additional 150 mg of ivacaftor in the evening, approximately 12 h later [ 39 , 40 ]. Gopalkumar Rakesh’s group reported the case of a 19-year- old CF patient diagnosed at aged 4 with F508del/1898 + 1G > A mutations and a sweat chloride level of 105 mmol/.…”

Section: Rescue Of Cftr Functionmentioning

confidence: 99%

Cystic Fibrosis Human Organs-on-a-Chip

et al. 2021

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Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene: the gene product responsible for transporting chloride and bicarbonate ions through the apical membrane of most epithelial cells. Major clinical features of CF include respiratory failure, pancreatic exocrine insufficiency, and intestinal disease. Many CF animal models have been generated, but some models fail to fully capture the phenotypic manifestations of human CF disease. Other models that better capture the key characteristics of the human CF phenotype are cost prohibitive or require special care to maintain. Important differences have been reported between the pathophysiology seen in human CF patients and in animal models. These limitations present significant limitations to translational research. This review outlines the study of CF using patient-derived organs-on-a-chip to overcome some of these limitations. Recently developed microfluidic-based organs-on-a-chip provide a human experimental model that allows researchers to manipulate environmental factors and mimic in vivo conditions. These chips may be scaled to support pharmaceutical studies and may also be used to study organ systems and human disease. The use of these chips in CF discovery science enables researchers to avoid the barriers inherent in animal models and promote the advancement of personalized medicine.

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“…These new therapies resulted in significant benefits for CF patients as described both in Randomized Controlled Trials (RCTs) and studies on data from national CF registries [13,14], but also some adverse events mainly consisting in cough, nasopharyngitis, oropharyngeal pain, and upper respiratory tract infection [15]. In addition, depression, anxiety, sleep paralysis with hypnopompic hallucinations [16] and testicular pain [17] have been reported after initiation of Trikafta therapy. Another common adverse event reported in patients treated with CFTR modulators is an abnormal liver function that is however moderate in severity and did not require drug discontinuation [18].…”

Section: Introductionmentioning

confidence: 99%

In silico drug repositioning on F508del-CFTR: A proof-of-concept study on the AIFA library

Orro

Uggeri

Rusnati

et al. 2021

European Journal of Medicinal Chemistry

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Computational drug repositioning is of growing interest to academia and industry, for its ability to rapidly screen a huge number of candidates in silico (exploiting comprehensive drug datasets) together with reduced development cost and time. The potential of drug repositioning has not been fully evaluated yet for cystic fibrosis (CF), a disease mainly caused by deletion of Phe 508 (F508del) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. F508del-CFTR is thus withheld in the endoplasmic reticulum and rapidly degraded by the ubiquitin/proteasome system. CF is still a fatal disease. Nowadays, it is treatable by some CFTR-rescuing drugs, but new-generation drugs with stronger therapeutic benefits and fewer side effects are still awaited. In this manuscript we report about the results of a pilot computational drug repositioning screening in search of F508del-CFTR-targeted drugs performed on AIFA library by means of a dedicated computational pipeline and surface plasmon resonance binding assay to experimentally validate the computational findings.

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Trikafta and Psychopathology in Cystic Fibrosis: A Case Report

Cited by 33 publications

References 12 publications

Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review

Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review

Cystic Fibrosis Human Organs-on-a-Chip

In silico drug repositioning on F508del-CFTR: A proof-of-concept study on the AIFA library

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