Sophie-Liliane Rosenke
Cystic Fibrosis is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, causing the production of thick and sticky secretions into the airways. This leads to organ damage, including damage to the lungs, a major cause of early mortality. Only in the last decade, CFTR modulators were introduced, which can correct the underlying dysfunction of the CFTR gene in 90% of patients. There are currently four CFTR modulators approved in the UK: Kalydeco (the longest serving), Orkambi, Symkevi and lastly Kaftrio, introduced in 2021.
A systematic review of the literature revealed Kalydeco and Kaftrio have the greatest treatment benefit with improved lung function, reduced pulmonary exacerbations and improved symptoms overall. CFTR agents presented an overall favourable safety profile with low discontinuation rates when compared to placebo.
A greater treatment response was observed in young patients and simulations have suggested starting treatment at an early age could significantly increase life expectancy and reduce the huge life-long treatment burden of conventional symptomatic treatments. The current CFTR modulators do not have a significant effect on patients with rare CFTR mutations (10%), meaning treatment for these individuals still needs to be researched and developed.