Cystic fibrosis in a transformative era: Adapting to changing mental health needs

Abstract

The emergence of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator therapies has significantly impacted the lives of people with cystic fibrosis (pwCF) and their families. In 2019, the triple combination CFTR modulator elexacaftor-tezacaftor-ivacaftor (ETI) was approved for pwCF aged 12 and older, with at least one F508del variant, based on supportive phase 3 efficacy and safety data [ [1] Heijerman H.G.M. McKone E.F. Downey D.G. Van Braeckel E. Rowe S.M. Tullis E. et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019; 394: 1940-1948 Google Scholar , [2] Zemanick E.T. Taylor-Cousar J.L. Davies J. Gibson R.L. Mall M.A. McKone E.F. et al. A phase 3 open-label study of elexacaftor/tezacaftor/ivacaftor in children 6 through 11 years of age with cystic fibrosis and at least one F508del allele. Am J Respir Crit Care Med. 2021; 203: 1522-1532 Google Scholar ]. ETI is estimated to be effective for 85% of the cystic fibrosis population, a far greater percent than previous CFTR therapies, though notably it is not effective for everyone. To date, the clinical impact of CFTR correction for most pwCF and its effects on multiple organ systems are very exciting and encouraging [ [3] Nichols D.P. Paynter A.C. Heltshe S.L. Donaldson S.H. Frederick C.A. Freedman S.D. et al. Clinical effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: a clinical trial. Am J Respir Crit Care Med. 2022; 205: 529-539 Google Scholar ]. However, real world experience also suggests a link between CFTR therapy and adverse cognitive and mental health symptoms, including insomnia, mental fogginess, neurocognitive adverse events, anxiety and depression [ 4 Tindell W. Su A. Oros S.M. Rayapati A. Rakesh G. Trikafta and psychopathology in cystic fibrosis: a case report. Psychosomatics. 2020; 61: 735-738 Google Scholar , 5 Dagenais R.V.E. Su V.C.H. Quon B.S. Real-world safety of CFTR modulators in the treatment of cystic fibrosis: a systematic review. J Clin Med. 2020; 10 Google Scholar , 6 Heo S. Young D.C. Safirstein J. Bourque B. Antell M.H. Diloreto S. et al. Mental status changes during elexacaftor/tezacaftor /ivacaftor therapy. J Cyst Fibros. 2022; 21: 339-343https://doi.org/10.1016/j.jcf.2021.10.002 Google Scholar ]. Research on the mental health (“MH”) implications of highly effective modulator therapies is still limited and the link is not fully understood or mapped out. Accordingly, the two papers in this issue of the journal [ [7] Arslan M. Chalmers S. Rentfrow K. Olson J.M. Dean V. Wylam M.E. Demirel N. Suicide attempts in adolescents with cystic fibrosis on Elexacaftor/Tezacaftor/Ivacaftor therapy. J Cyst Fibros. 2023; (XXXXXX) Google Scholar , [8] Milo F. Ciciriello F. Alghisi F. Tabarini P. Lived experiences of people with Cystic Fibrosis that were not eligible for elexacaftor-tezacaftor-ivacaftor (ETI): a qualitative study. J Cyst Fibros. 2023; (XXXXX) Google Scholar ] provide valuable insights from real-world experience with regard to the psychological experience of living with CF and the implications of the new modulator therapies on those who are eligible, those who may need to discontinue treatment and those who are not eligible.