Real-world Efficacy and Safety of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator Therapy in Adult Patients With Cystic Fibrosis (CF)

Real-world Efficacy and Safety of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator Therapy in Adult Patients With Cystic Fibrosis (CF)

In this trial real-world data on the safety (side effects and medication interactions) and efficacy (evolution of lung function testing, chronic bacterial airway infection, quality of life and endo- and exocrine pancreatic function) will be collected in adult people with cystic fibrosis (pwCF) eligible for elexacaftor-tezacaftor-ivacaftor (ETI) up until 2 years after the start of this therapy.

PwCF group A: CFTR-modulator-naive pwCF eligible for ETI (based on age and CFTR genotype) PwCF group B: pwCF already on CFTR modulating therapy (i.e. ivacaftor-lumacaftor or ivacaftor-tezacaftor) and switching to ETI. Patients in both groups will undergo these examinations: Physical examination (including weight) Anamnesis for current and recent medication use (including dosage of pancreatic enzymes) and for acute respiratory exacerbations Lung function testing including spiometry, multiple breath washout testing and fractional exhaled nitric oxide Blood sampling: liver function tests, creatine kinase, albumin, PT, red and white blood cell count, platelet count Sputum/cough swab sampling fecal elastase measurement Cystic fibrosis questionnaire-revised (CFQ-R) questionnaire Patient health questionnaire-9 (PHQ-9) questionnaire General anxiety disorder-7 (GAD-7) questionnaire Sino-nasal outcome test-22 (SNOT-22) questionnaire These will be performed at baseline (prior to the start of ETI, on the same day of start of ETI), and every 3 months (+/- 7 days) thereafter. A blood sample will also be performed 14 (+/- 7 days) days after start of ETI (for safety). Fecal elastase measurement will only be performed at baseline if not available in the patient's medical record, and only 6 months after start of ETI.

pwCF which are CFTR-modulator naive and pwCF previously treated with a CFTR-modulator (i.e. tezacaftor-ivacaftor or lumacaftor-ivacaftor) will undergo standard-of-care examinations as well as examinations in the context of this trial (i.e. CFQ-R, PHQ-9, GAD-7 and SNOT-22 questionnaires, fecal elastase measurement)

the concentration of elastase (a pancreatic enzyme) in feces before and 6 months after start of CFTR modulating treatment, as a surrogate measure for pancreatic function

Inclusion Criteria: eligible for ETI (i.e. age above 18 years and CFTR genotype F508del/any) based on reimbursement criteria in Belgium Exclusion Criteria: inability to perform lung function testing