Comparison of Long Term Effects of Treatment of Different CFTR Modulators in People With Cystic Fibrosis

Cystic fibrosis transmembrane conductance regulator modulators (CFTRm) represent a breakthrough in the treatment of people with cystic fibrosis (PwCF), offering improvements in health outcomes and quality of life (QoL) previously unattainable.

To descriptively evaluate 12-month outcomes during treatment with three CFTRm therapies in a real-world cohort of children and adults with CF.

This prospective, observational study included 146 PwCF aged 2-56 years treated at two Polish CF centres. Patients received lumacaftor/ivacaftor (LUM/IVA), tezacaftor/ivacaftor (TEZ/IVA) or elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA). Assessments were conducted at baseline and every 3 months over 12 months. Parameters evaluated included spirometry, impulse oscillometry (IOS), lung clearance index (LCI), anthropometric data, serum vitamin D3, sweat chloride (SwCl), lung imaging (Brasfield score), general clinical status - Schwachman-Kulczycki (S-K score), and quality of life (QoL). Statistical analyses were performed using the software R (v. 4.4.1).

Most parameters improved over time, with response magnitude varying by treatment. Significant improvements were observed in forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), maximal expiratory flow at 50% of vital capacity (MEF₅₀), LCI, most IOS parameters, SwCl, anthropometric parameters, Brasfield and S-K scores. Vitamin D3 concentrations and resistance at 5 Hz (R5) did not change significantly. All therapies led to better QoL.

CFTRm - particularly ELX/TEZ/IVA - demonstrated substantial clinical benefits across age groups. The treatment effect varied over time in the majority of patients. Different CFTRm's impact on respiratory function, nutritional status, and well-being underscores the importance of personalized approaches in CF care.