Biliary disease and cholecystectomy after initiation of elexacaftor/ivacaftor/tezacaftor in adults with cystic fibrosis

Safirstein, Julie; Grant, Jonathan J.; Clausen, Emily; Savant, Deepika; Dezube, Rebecca; Hong, Gina

doi:10.1016/j.jcf.2020.07.014

Cited by 28 publications

(22 citation statements)

References 13 publications

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“…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%

“…Given the relatively recent market approval in some countries, limited data were available regarding real-world AEs with ELX/TEZ/IVA. One case series reported on seven adults who experienced biliary colic following initiation of ELX/TEZ/IVA; all but one patient received a cholecystectomy [53]. Only one of the seven patients was CFTR modulator naïve prior to ELX/TEZ/IVA, and five of the patients had chronic cholecystitis and cholelithiasis [53].…”

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

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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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: Description Of Studiesmentioning

confidence: 99%

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

confidence: 99%

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

Dagenais

Quon

2020

JCM

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“…Almost all the patients were diagnosed with acute or chronic cholecystitis and had cholecystectomies despite discontinuing therapy. All patients resumed therapy postcholecystectomy 35 . Discontinuation rates were fairly low in phase 3 trials with one trial having no adverse events that led to treatment discontinuation and the other trial having only two patients discontinue therapy due to a rash and due to portal hypertension in a patient with preexisting cirrhosis 33,34 .…”

Section: Commentmentioning

confidence: 97%

A current review of the safety of cystic fibrosis transmembrane conductance regulator modulators

Gavioli¹,

Guardado²,

Haniff³

et al. 2020

J Clin Pharm Ther

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What is known and objective Treatment with cystic fibrosis transmembrane conductance regulator (CFTR) modulators has led to improved clinical outcomes and an increase in lifespans of cystic fibrosis (CF) patients. As CF patients continue to live longer, they are at risk for developing adverse drug reactions associated with polypharmacy and CFTR modulators. Comment The authors aim to describe safety concerns of the current combination CFTR modulators, based upon a literature review, including notable safety concerns and recommendations for drug‐drug interactions. What is new and conclusion Cystic fibrosis transmembrane conductance regulator agents are generally well tolerated with low discontinuation rates when compared to placebo. Elevations in liver enzymes and drug‐drug interactions are the most notable safety concerns. Additionally, lumacaftor/ivacaftor has shown more respiratory‐related adverse events and drug‐drug interactions compared to elexacaftor/tezacaftor/ivacaftor and tezacaftor/ivacaftor. Postmarketing studies are needed to determine long‐term safety concerns.

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“…Remarkably, the triple therapy is particularly well-tolerated. Liver enzyme monitoring is recommended as with ivacaftor, and there have been reports of biliary colic and transient testicular pain, as well as increased fertility in women [89][90][91]. Delayed drug interaction between azithromycin and the TEZ/IVA combination manifested by first degree heart block has also been reported [92].…”

Section: Tezacaftor-ivacaftormentioning

confidence: 99%

New Therapies to Correct the Cystic Fibrosis Basic Defect

Bergeron

Cantin

2021

IJMS

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Rare diseases affect 400 million individuals worldwide and cause significant morbidity and mortality. Finding solutions for rare diseases can be very challenging for physicians and researchers. Cystic fibrosis (CF), a genetic, autosomal recessive, multisystemic, life-limiting disease does not escape this sad reality. Despite phenomenal progress in our understanding of this disease, treatment remains difficult. Until recently, therapies for CF individuals were focused on symptom management. The discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and its product, a protein present at the apical surface of epithelial cells regulating ion transport, allowed the scientific community to learn about the basic defect in CF and to study potential therapies targeting the dysfunctional protein. In the past few years, promising therapies with the goal to restore CFTR function became available and changed the lives of several CF patients. These medications, called CFTR modulators, aim to correct, potentialize, stabilize or amplify CFTR function. Furthermore, research is ongoing to develop other targeted therapies that could be more efficient and benefit a larger proportion of the CF community. The purpose of this review is to summarize our current knowledge of CF genetics and therapies restoring CFTR function, particularly CFTR modulators and gene therapy.

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Biliary disease and cholecystectomy after initiation of elexacaftor/ivacaftor/tezacaftor in adults with cystic fibrosis

Cited by 28 publications

References 13 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

A current review of the safety of cystic fibrosis transmembrane conductance regulator modulators

New Therapies to Correct the Cystic Fibrosis Basic Defect

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