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

Abstract

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.