The New Landscape of Cystic Fibrosis in the Era of Highly Effective Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy.

Abstract

Background: For many years, the management of cystic fibrosis has had a personalised character. We have now entered an era of therapy based on a patient's specific genotype. Clinical trials have confirmed the efficacy and safety of cystic fibrosis transmembrane conductance regulator modulator therapies, including ivacaftor as monotherapy and triple-drug combinations, such as elexacaftor/tezacaftor/ivacaftor and vanzacaftor/tezacaftor/deutivacaftor. These therapies result in substantial and sustained improvements in lung function, a reduction in the frequency of bronchopulmonary exacerbations, enhanced nutritional status, and an improved quality of life. These clinical outcomes have been correlated with a marked reduction of sweat chloride values.

Material and methods: Early initiation of therapy is crucial to halt disease progression or even reverse disease-related complications, which have even been observed in children aged six to twelve years. Initiating treatment in even younger children before the onset of clinical symptoms offers the possibility of a much later disease manifestation or even absence of symptoms. Nevertheless, careful evaluation of these therapies' long-term effects on the respiratory system and other organs remains necessary.

Results: According to current knowledge, patients continue to require regular follow-up by a multidisciplinary care team and ongoing adjustment of both modulator and symptomatic therapies to meet individual needs.

Conclusion: As patient life expectancy continues to increase, comorbidities such as arterial hypertension, hypercholesterolaemia, cardiovascular disease, and malignancies will assume greater clinical importance. Selecting optimal therapeutic strategies remains a significant clinical challenge due to the numerous potential interactions between modulators and other medications.