Early use of teduglutide in paediatric patients with intestinal failure is associated with a greater response rate: a multicenter study.

Teduglutide is a glucagon-like-peptide-2 analogue that reduces the need for parenteral support in patients with short bowel syndrome (SBS). Nevertheless, data about long-term therapy with teduglutide in children are still scarce. Our objective was to describe the real-life experience with teduglutide in children with SBS over the last 5 years in Spain. This was a national multicentre and prospective study of paediatric patients with intestinal failure (IF) treated with teduglutide for at least 3 months. The data included demographic characteristics, medical background, anthropometric data, laboratory assessments, adverse events, and parenteral nutrition (PN) requirements. Treatment response was defined as a > 20% reduction in the PN requirement. The data were collected from the Research Electronic Data Capture (REDCap) database. Thirty-one patients from seven centres were included; the median age at the beginning of the treatment was 2.3 (interquartile range (IQR) 1.4-4.4) years; and 65% of the patients were males. The most frequent cause of IF was SBS (94%). The most common cause of SBS was necrotizing enterocolitis (35%). The median residual bowel length was 29 (IQR 12-40) cm. The median duration of teduglutide therapy was 19 (IQR 12-36) months, with 23 patients (74%) treated for > 1 year and 9 treated for > 3 years. The response to treatment was analysed in 30 patients. Twenty-four patients (80%) had a reduction in their weekly PN energy > 20% and 23 patients (77%) had a reduction in their weekly PN volume > 20%. Among the responders, 9 patients (29%) were weaned off PN, with a median treatment duration of 6 (IQR 4.5-22) months. The only statistically significant finding demonstrated an association between a > 20% reduction in the weekly PN volume and a younger age at the start of treatment (p = 0.028).   Conclusions: Teduglutide seems to be an effective and safe treatment for paediatric patients with IF. Some patients require a prolonged duration of treatment to achieve enteral autonomy. Starting treatment with teduglutide at a young age is associated with a higher response rate. What is Known: •  Glucagon-like peptide-2 (GLP-2) plays a crucial role in the regulation of intestinal adaptation in short bowel syndrome (SBS). Teduglutide is a GLP-2 analog that reduces the need for parenteral support in patients with SBS. • Data about long-term therapy with teduglutide in children in real life are still scarce. What is New: • Most pediatric patients with SBS respond in a satisfactory manner to teduglutide treatment. The occurrence of long-term adverse effects is exceptional. • Starting treatment with the drug at a young age is associated with a greater response rate.

[Ledipasvir/sofosbuvir combination for chronic hepatitis C infection in children and adolescents]. / Combinación de ledipasvir/sofosbuvir como tratamiento de la infección crónica por hepatitis C.

INTRODUCTION: Hepatitis C virus infection is world health problem. The aim of this study was to assess the safety and efficacy of ledipasvir/sofosbuvir combination in chronic Hepatitis C Virus (HCV) genotype 1 and 4 infection in paediatric patients. METHODS: Eligible patients to be treated with ledipasvir/sofosbuvir were patients from 6 to 18 years old with a chronic HCV genotype 1 or 4 infection. The duration and doses of antiviral drugs were changed depending on patient age, fibrosis stage, and PEGylated interferon+ribavirin experience status. The primary efficacy endpoint was the percentage of patients with a sustained virological response 12 weeks post-treatment. RESULTS: A total of nine patients (7 males) with a median age of 14.8 years (8.48-17.91) were treated with ledipasvir/sofosbuvir combination. Five patients received previous treatment with PEGylated interferon+ribavirin during a median of 8.5 months (3-12 months). Eight patients had some degree of fibrosis (1 patient presented with F1, three patients F2, 2 patients F3, and 2 patients F4). The median pre-treatment viral load was 6.2 Log [5.9-6.8] with the HCV RNA becoming negative six weeks after starting the treatment in 100% of the patients. All patients maintained a sustained viral response at 12 weeks. Three patients (33.3%) had some type of adverse effect (2 headache and one oral thrush). The median post-treatment follow-up was 24 weeks (12-104). CONCLUSIONS: Treatment with ledipasvir/sofosbuvir in paediatric patients with chronic HCV infection genotype 1 and 4 is safe and effective with SVR12 and similar to those reported in adults.

Combinación de ledipasvir/sofosbuvir como tratamiento de la infección crónica por hepatitis C / Ledipasvir/sofosbuvir combination for chronic hepatitis C infection in children and adolescents

Introducción: El objetivo del estudio fue evaluar la seguridad y la eficacia de la combinación de ledipasvir/sofosbuvir en la infección crónica por el genotipo 1 y 4 del virus de la hepatitis C (VHC) en pacientes pediátricos. Métodos: Se incluyó a pacientes de entre 6 y 18 años. La duración y la dosis de los fármacos antivirales se administraron según la edad del paciente, el estadio de fibrosis y los tratamientos previos con interferón pegilado y ribavirina. La variable principal de eficacia fue el porcentaje de pacientes con una respuesta virológica sostenida 12 semanas (RVS12) después del tratamiento. Resultados: Nueve pacientes con una mediana de edad de 14,8 años (8,48-17,91) fueron tratados con combinación de ledipasvir/sofosbuvir. Cinco pacientes habían recibido previamente tratamiento con interferón pegilado + ribavirina. Ocho pacientes tenían algún grado de fibrosis. La mediana de la carga viral previa al tratamiento fue de 6,2 log (5,9-6,8) con negativización del ARN del VHC 6 semanas después de comenzar el tratamiento en el 100% de los pacientes. Todos los pacientes mantuvieron una respuesta viral sostenida a las 12 semanas. Tres pacientes (33,3%) tuvieron algún tipo de efecto adverso (2 dolores de cabeza y un afta oral). La mediana de seguimiento posterior al tratamiento fue de 24 semanas (12-104). Conclusiones: El tratamiento con ledipasvir/sofosbuvir en pacientes pediátricos con infección crónica por VHC de genotipo 1 y 4 es seguro y efectivo con RVS12, similar a lo reportado en adultos

Introduction: Hepatitis C virus infection is world health problem. The aim of this study was to assess the safety and efficacy of ledipasvir/sofosbuvir combination in chronic Hepatitis C Virus (HCV) genotype 1 and 4 infection in paediatric patients. Methods: Eligible patients to be treated with ledipasvir/sofosbuvir were patients from 6 to 18 years old with a chronic HCV genotype 1 or 4 infection. The duration and doses of antiviral drugs were changed depending on patient age, fibrosis stage, and PEGylated interferon+ribavirin experience status. The primary efficacy endpoint was the percentage of patients with a sustained virological response 12 weeks post-treatment. Results: A total of nine patients (7 males) with a median age of 14.8 years (8.48-17.91) were treated with ledipasvir/sofosbuvir combination. Five patients received previous treatment with PEGylated interferon + ribavirin during a median of 8.5 months (3-12 months). Eight patients had some degree of fibrosis (1 patient presented with F1, three patients F2, 2 patients F3, and 2 patients F4). The median pre-treatment viral load was 6.2 Log [5.9-6.8] with the HCV RNA becoming negative six weeks after starting the treatment in 100% of the patients. All patients maintained a sustained viral response at 12 weeks. Three patients (33.3%) had some type of adverse effect (2 headache and one oral thrush). The median post-treatment follow-up was 24 weeks (12-104). Conclusions: Treatment with ledipasvir/sofosbuvir in paediatric patients with chronic HCV infection genotype 1 and 4 is safe and effective with SVR12 and similar to those reported in adults