Response to CFTR Modulators in CF Patients Under 18 Years

Evaluation of the Response to CFTR Modulators in Patients With Cystic Fibrosis Less Than 18 Years of Age

CFTR modulators should improve the prognosis of Cystic Fibrosis. Identifying patients under the age of 18 responding to CFTR modulators as well as detecting possible toxicity is an important medical objective given the potential side effects and the high cost of these molecules.

This observational follow-up cohort study is carried out as part of routine care.

The main objective is to assess the evolution of pulmonary structural impairment by low-dose CF scan at the end of the first year of CFTR modulator therapy.

The secondary objectives are to evaluate structural impairment at low dose scan at 3 years and 5 years of CFTR modulator treatment, the evolution of respiratory functional parameters, growth, puberty, lung infection, sweat test, quality of life and pancreatic function, as well as tolerance of modulators including liver toxicity.

Cystic fibrosis (CF) is a deadly disease. This is due to overinfected chronic obstructive pulmonary disease that progresses to end-stage respiratory failure. CFTR modulators should improve the prognosis of CF, as they may slow the progression of patients' lung disease. Assessing their impact in the paediatric population is becoming a major issue. Children and adolescents under the age of 18 are a target cohort because they have a lung disease that is still poorly developed. Early prescription of CFTR modulators is therefore a priority but requires evidence of absence of toxicity. Identifying patients under the age of 18 responding to CFTR modulators as well as detecting possible toxicity, is an important medical objective given the potential side effects and the high cost of these molecules.

The outcomes previously used in Phase III studies (FEV1, frequency of exacerbations, nutritional status) are insufficiently sensitive in this population.

Other criteria need to be analyzed to identify the response to CFTR modulators in the short and medium term. The investigators hypothesize that the assessment of pulmonary structural impairment by low-dose lung CT-scan as part of routine care could be a much more sensitive criterion for the development of lung disease under CFTR modulators.

This observational follow-up cohort study is carried out as part of routine care. It does not involve a specific collection for research. Excess bronchial secretions and blood will be kept instead of being discarded in the event of a possible requalification for research.

The main objective is to assess the evolution of pulmonary structural impairment by low-dose CF scan at the end of the first year of CFTR modulator therapy The secondary objectives are to assess following criteria

• Tolerance of modulators in this age group, including screening for bronchial reactivity at treatment, early liver toxicity
• Longitudinal evolution of pulmonary structural impairment by low dose scan at 3 years and 5 years of CFTR modulator treatment
• Evolution of respiratory functional parameters
• Measurement by spirometry and plethysmography
• Lung clearance index (if possible)
• Longitudinal evolution of bacterial colonization, compared to the year prior to modulating treatment
• Exacerbations: number, duration, days of antibiotics, hospitalizations, return to stable condition
• Colonization of bronchial secretions
• Changes in quality of life
• Evolution of the sweat test
• Longitudinal evaluation of pancreatic function
• Longitudinal evaluation of growth and puberty compared to the year prior to CFTR modulator
• Growth speed, and bone age
• Bone mineralization, body composition (if possible)
• Pubertal markers from 9 years in girls and 10 years in boys
• Evaluation of glycemic dysregulation if present
• Preservation of samples taken as part of routine care (serum, bronchial secretions) for possible research use

Inclusion Criteria:

Children with cystic fibrosis under the age of 18 under CFTR modulator therapy

Exclusion Criteria:

• Patients with cystic fibrosis without indication for CFTR modulator therapy
• Patients over the age of 18
• Pregnant or lactating women