Trials and tribulations of highly effective modulator therapies in cystic fibrosis

Nathan Lieu; Bernadette J Prentice; Penelope Field; Dominic A Fitzgerald

doi:10.1016/j.prrv.2023.09.001

Trials and tribulations of highly effective modulator therapies in cystic fibrosis

Paediatr Respir Rev. 2023 Dec:48:10-19. doi: 10.1016/j.prrv.2023.09.001. Epub 2023 Sep 15.

Authors

Nathan Lieu¹, Bernadette J Prentice², Penelope Field³, Dominic A Fitzgerald⁴

Affiliations

¹ Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia, 2145; Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia. Electronic address: [email protected].
² Department of Respiratory Medicine, Sydney Children's Hospital, Randwick, Sydney, New South Wales, Australia, 2031; Discipline of Paediatrics and Child Health, UNSW, Sydney, New South Wales, Australia.
³ Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia, 2145; Department of Respiratory Medicine, Sydney Children's Hospital, Randwick, Sydney, New South Wales, Australia, 2031; Discipline of Paediatrics and Child Health, UNSW, Sydney, New South Wales, Australia.
⁴ Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia, 2145; Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia.

PMID: 37914566
DOI: 10.1016/j.prrv.2023.09.001

Abstract

Highly effective modulator therapies (HEMTs) have revolutionised the management approach of most patients living with cystic fibrosis (CF) who have access to these therapies. Clinical trials have reported significant improvements across multiorgan systems, with patients surviving longer. However, there are accumulating case reports and observational data describing various adverse events following initiation of HEMTs including drug-to-drug interactions, drug induced liver injury, Stevens-Johnson syndrome, and neurocognitive symptoms including psychosis and depression, which have required discontinuation of therapy. Current clinical trials are assessing efficacy in younger patients with CF, yet long-term studies are also required to better understand the safety profile in the real-world setting across all ages and the impact of HEMT dose alteration or discontinuation.

Keywords: Adverse events; Cystic fibrosis; Elexacaftor-tezacaftor-ivacaftor; Highly effective modulator therapies [HEMT].

Publication types

Review

MeSH terms

Aminophenols
Chloride Channel Agonists
Cognition
Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis* / drug therapy
Humans
Mutation

Substances

Cystic Fibrosis Transmembrane Conductance Regulator
Aminophenols
Chloride Channel Agonists