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 modula...

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Main Authors: Ruth García Romero, Concepción López Cárdenes, Elena Crehuá Gaudiza, Marina Álvarez Beltrán, Mercedes Murray Hurtado, Carlos Tutau Gómez, Inés Loverdos Eseverri, Encarni Torcuato Rubio, Camila García Volpe, Enrique Salcedo Lobato, María Medina Martínez, Carmen Martin Fernández, Ana Moreno Álvarez, Ana Reyes Domínguez, David González Jiménez, Saioa Vicente Santamaría, Ana Tabares González, Jose Ramon Gutierrez Martinez, Sara Sierra San Nicolás, Pilar Ortiz Pérez, Luis Peña Quintana
Format: Article
Language:Spanish
Published: Elsevier 2025-05-01
Series:Anales de Pediatría (English Edition)
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Online Access:http://www.sciencedirect.com/science/article/pii/S2341287925001243
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Summary: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. Resumen: Introducción: Los tratamientos con moduladores de la proteína CFTR han mejorado la salud respiratoria y digestiva de los pacientes con fibrosis quística. Objetivo: Analizar los cambios en la inflamación intestinal mediante estudio de la calprotectina fecal en pacientes con fibrosis quística durante el tratamiento con moduladores. Material y métodos: Estudio multicéntrico prospectivo de los cambios en la calprotectina fecal de pacientes con fibrosis quística tratados con moduladores, comparando aquellos constituidos por 2 moléculas (lumacaftor/ivacaftor o tezacaftor/ivacaftor), con los de 3 moléculas (elexacaftor/tezacaftor/ivacaftor). Se recogen datos antes de iniciar el tratamiento, a los 6 y a los 12 meses. Resultados: Análisis de 117 pacientes (69% F508del/F508del). Mediana basal de calprotectina fecal 49 mcg/g (RIC 23–108); 48.7% con >50 mcg/g; 11% con >250 mcg/g. Hubo disminución de calprotectina fecal en ambos grupos, siendo mayor en aquellos con elexacaftor/tezacaftor/ivacaftor. Se observó una disminución progresiva de los valores anormales (>50 mcg/g) a los 6 meses 48.7% vs 33,1% (p = 0,0067) y a los 12 meses 54% vs 33,5% (p = 0,0218). En el grupo elexacaftor/tezacaftor/ivacaftor, sólo 2 pacientes a los 6 meses y 1 paciente a los 12 meses, tenían >250 mcg/g. El cambio estimado (IC del 95%) a 12 meses en el grupo con triple terapia en comparación con el otro grupo fue de −133 mcg/g (−254−13, p = 0,030); y ajustado por sexo, probióticos y Pseudomonas aeruginosa de −130 mcg/g (−259 to −1, p = 0,049). Conclusiones: El tratamiento con moduladores CFTR reduce la inflamación intestinal en pacientes con fibrosis quística, siendo la mejoría más destacada en pacientes tratados con la triple terapia.
ISSN:2341-2879