Evolución clínico funcional de pacientes con fibrosis quística tratados con lumacaftor/ivacaftor en un centro pediátrico. Serie de casos / Clinical and functional course of patients with cystic fibrosis treated with lumacaftor/ivacaftor at a children's hospital. A case series

Los moduladores de la proteína reguladora transmembrana de fibrosis quística (CFTR) tratan el defecto de esta proteína. El objetivo es describir la evolución de niños con fibrosis quística tratados con lumacaftor/ivacaftor. Se trata de una serie de 13 pacientes de 6 a 18 años con ≥ 6 meses de tratamiento. Se analizaron el volumen espiratorio forzado en el primer segundo (VEF1), puntaje Z del índice de masa corporal (IMC), antibioticoterapia/año, antes del tratamiento y durante 24 meses posteriores. A los 12 meses (9/13) y 24 meses (5/13), la mediana de cambio del porcentaje del predicho VEF1 (ppVEF1) fue de 0,5 pp [-2-12] y 15 pp [8,7-15,2], y del puntaje Z de IMC de 0,32 puntos [-0,2-0,5] y 1,23 puntos [0,3-1,6]. El primer año (11/13) la mediana de días de uso de antibiótico disminuyó de 57 a 28 (oral) y de 27 a 0 (intravenoso). Dos niños evidenciaron eventos adversos asociados.

Cystic fibrosis transmembrane regulator (CFTR) modulators treat defective CFTR protein. Our objective is to describe the course of children with cystic fibrosis treated with lumacaftor/ivacaftor. This is a case series of 13 patients aged 6 to 18 years with ≥ 6 months of treatment. Forced expiratory volume in the first second (FEV1), body mass index (BMI) Z-score, antibiotic therapy/year, before treatment and for 24 months after treatment were analyzed. At 12 months (9/13) and 24 months (5/13), the median change in the percent predicted FEV1 (ppFEV1) was 0.5 pp (-2­12) and 15 pp (8.7­15.2) and the BMI Z-score was 0.32 points (-0.2­0.5) and 1.23 points (0.3­1.6). In the first year, in 11/13 patients, the median number of days of antibiotic use decreased from 57 to 28 (oral) and from 27 to 0 (intravenous). Two children had associated adverse events.

Pediatric population with cystic fibrosis in the centre of Portugal: candidates for new therapies

Abstract Objectives: Cystic fibrosis (CF) is a severe autosomal recessive disease that results from mutations in a gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, a chloride channel. This study aims to characterize the clinical and genetic features of a cohort of pediatric people with CF (PwCF) in the center of Portugal and to determine which ones are candidates for the new drugs modulating the CFTR channel. Methods: A review of the demographic, genetic and clinical characteristics of PwCF undergoing follow-up at a CF reference center was carried out. Results: Twenty-three PwCF (12 male), with a median age of 12 years, were followed up. All patients carry the F508del mutation in at least one allele. Fifteen PwCF were F508del-homozygous, median BMI z-score was -0.13, all are pancreatic insufficient and median FEV1 value was 78.1%. These PwCF are eligible for dual therapy (lumacaftor/tezacaftor+ivacaftor) and for triple therapy (tezacaftor+ivacaftor+elexacaftor). PwCF with 711 +1G->T (n = 2), 2184insA (n = 1) mutations and a novel mutation c.3321dup (n = 1) have minimal function mutation and patients with a residual function mutation: R334W (n = 3) and P5L (n = 1) have a less severe phenotype. All these patients, because they also carry F508del mutation, are elegible to triple therapy. Conclusions: Genetic and molecular characterization of PwCF poses an important step not just for CF diagnosis and prognosis which is tightly correlated with the clinical phenotype, but also for the eligibility of CFTR modulator drugs.

Moduladores mejoran la función pulmonar en la mutación más frecuente de la fibrosis quística / Proteine modulators improve pulmonary function in the most common cystic fibrosis mutation

Un tópico de análisis crítico es un resumen estandarizado que se organiza en torno a una pregunta clínica estructurada, realiza una revisión crítica y resalta la relevancia de sus resultados aplicados a nuestra realidad. El estudio analizado evalúa en 1100 pacientes de 12 años o más portadores de fibrosis quística (FQ) homocigotos para la mutación más frecuente phe508del CFTR, la terapia combinada de dos moduladores de la proteína CFTR, comparado con placebo, la que mostró mejoría significativa de la función pulmonar (VEF1) de 2.6 a 4 puntos porcentuales 1. Estos resultados proponen un tratamiento curativo al 50 por ciento de los pacientes en USA y al 15 por ciento en nuestro país, una vez superado los costos.

A CAT is a standardized summary of research evidence organized around a clinical question, aimed to provide a critique of the research and a statement of the clinical relevance of results. In the analyzed paper, the authors evaluated 1100 patients with cystic fibrosis (CF) 12 years and older with two copies of phe508del CFTR genetic mutation, the combination therapy of two CFTR modulators led to mean absolute improvements in lung function (VEF1) between 2.6 and 4 percentage points, which was statistically significant. These results are promising for the 50 percent of the USA CF population and 15 percent of the CF Chilean population.

Moduladores mejoran la función pulmonar en la mutación más frecuente de la fibrosis quística / Proteine modulators improve pulmonary finction in the most common cystic fibrosis mutation

Un tópico de análisis crítico es un resumen estandarizado que se organiza en torno a una pregunta clínica estructurada, realiza una revisión crítica y resalta la relevancia de sus resultados aplicados a nuestra realidad. El estudio analizado evalúa en 1100 pacientes de 12 años o más portadores de fibrosis quística (FQ) homocigotos para la mutación más frecuente phe508del CFTR, la terapia combinada de dos moduladores de la proteína CFTR, comparado con placebo, la que mostró mejoría significativa de la función pulmonar (VEF1) de 2.6 a 4 puntos porcentuales1. Estos resultados proponen un tratamiento curativo al 50% de los pacientes en USA y el 15% en nuestro país, una vez superado los costos. (AU)

A CAT is a standardized summary of research evidence organized around a clinical question, aimed to provide a critique of the research and a statement of the clinical relevance of results. In the analyzed paper, the authors evaluated 1100 patients with cystic fibrosis (CF) 12 years and older with two copies of phe508del CFTR genetic mutation, the combination therapy of two CFTR modulators led to mean absolute improvements in lung function (VEF1) between 2.6 and 4 percentage points, which was statistically significant. These results are promising for the 50% of the USA CF population and 15% of the CF Chilean population. (AU)