Improvement of intestinal inflammation after treatment with CFTR modulators in cystic fibrosis patients

Introduction: Treatments with CFTR protein modulators have improved respiratory and digestive health in patients with cystic fibrosis. Objective: To assess changes in intestinal inflammation through the analysis of fecal calprotectin in patients with cystic fibrosis during treatment with CFTR modulators. Material and methods: Prospective multicenter study of changes in fecal calprotectin in patients with cystic fibrosis treated with CFTR modulators, comparing double combinations (lumacaftor/ivacaftor or tezacaftor/ivacaftor) and triple combinations (elexacaftor/tezacaftor/ivacaftor). We collected data before treatment initiation and at 6 and 12 months. Results: Analysis of 117 patients (69% with F508del/F508del). The median baseline fecal calprotectin level was 49 mu g/g (IQR: 23-108); 48.7% had median levels greater than 50 mu g/g and 11% levels greater than 250 mu g/g. Fecal calprotectin decreased in both groups, with a greater decrease in patients treated with elexacaftor/tezacaftor/ivacaftor. We found a progressive decrease in abnormal values (> 50 mu g/g) at 6 months (48.7% vs 33.1%; P = .0067) and at 12 months (54% vs 33.5%; P = .0218). In the elexacaftor/tezacaftor/ivacaftor group, only two patients at 6 months and one patient at 12 months had levels greater than 250 mu g/g. The estimated change at 12 months in the triple therapy group compared to the other group was-133 mu g/g (95% CI: -254 to-13; P = .030); and, adjusting for sex, probiotics and Pseudomonas aeruginosa, -130 mu g/g (-259 to-1; P = .049). Conclusions: Treatment with CFTR modulators reduces intestinal inflammation in patients with cystic fibrosis, with a greater decrease in patients treated with triple therapy. (c) 2025 Asociacio<acute accent>n Espanola de Pediatr<acute accent>& imath;a. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).