Improvement of iron status with elexacaftor tezacaftor ivacaftor therapy is associated with the correction of systemic inflammation and improvement of lung function: a one-year prospective study

Iron deficiency (ID) is frequent in adult patients with cystic fibrosis (pwCF). The effect of elexacaftor-tezacaftor-ivacaftor (ETI) on iron metabolism has rarely been reported. We aimed to study the trends and variables associated with iron store modulation under ETI. We conducted a prospective adult cohort in two referral centres for pwCF. Iron supplementation during the follow-up was an exclusion criterion. Clinical, biological data and pulmonary function tests were collected prospectively at ETI initiation (V0) and after 1 year of ETI (V12). The presence of Pseudomonas aeruginosa in forced sputum was assessed at V0 and V12. 220 (87 women) pwCF among the 278 screened were included. At V0, ID prevalence was 58% and was significantly associated with female sex and lower forced expiratory volume (FEV1). At V12, ID prevalence decreased significantly from 58 to 31% (p = 0.001). A significant decrease of C reactive protein and total globulins was found at V12. 60% of patients with ID at V0 achieved normalization of iron status at V12 with a significant association with the increase of FEV1 (moderate size effect: 0.68). A lower decrease of C reactive protein was significantly associated with the onset of ID in a small sample of patients (p < 0.001). The disappearance of Pseudomonas aeruginosa in sputum at V12 was not correlated to the evolution of iron status under ETI. ETI was associated with a decrease of ID prevalence, and improvement of pulmonary function and a correction of systemic inflammation.