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 aata 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 µg/g (IQR, 23-108); 48.7% had median levels greater than 50 µg/g and 11% levels greater than 250 µg/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 µg/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 µg/g. The estimated change at 12 months in the triple therapy group compared to the other group was -133 µg/g (95% CI, -254 to -13; P = .030); and, adjusting for sex, probiotics and Pseudomonas aeruginosa, -130 µg/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.