Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have changed
the clinical landscape of cystic fibrosis (CF) by improving clinically significant
outcome measures and quality of life of people with CF (pwCF). There are now long-term
data showing improved 5-year survival with the use of ivacaftor, and the field continues
to evolve at a rapid pace with the continued development of highly effective CFTR
modulators. While the randomized controlled trials of CFTR modulators excluded patients
with severe lung disease (forced expiratory volume in 1 second <40% predicted), observational
data based on case reports and registry data show similar benefits in those with advanced
lung disease. This has altered clinical practice particularly as it pertains to the
role of lung transplantation in CF. This article describes the impact of highly effective
modulator therapy (HEMT) on the natural history of CF and the influence on the timing
of referral and consideration of listing for lung transplantation. CF clinicians play
a pivotal role to ensure that the impetus of the CF foundation consensus guidelines
to facilitate timely referral for lung transplantation is not lost among the excitement
of anticipated sustained benefit from HEMT. While the widespread availability of elexacaftor/tezacaftor/ivacaftor
over the past 2 years has been associated with a sharp drop in the number of people
referred for consideration for lung transplantation and the number of people wait-listed
for lung transplantation, it is difficult to accurately determine the true impact
due to the confounding effect of the coronavirus disease 2019 pandemic. It is expected
that lung transplantation will remain an important treatment for a smaller number
of pwCF. Lung transplantation offers survival benefits in CF, and there remains an
imperative to ensure timely consideration of lung transplantation in patients with
advanced disease to further reduce the number of pwCF dying without consideration
of lung transplant.
Keywords
cystic fibrosis - CFTR modulators - highly effective modulator therapy
