Efficacy and Safety of Teduglutide in Infants and Children With Short Bowel Syndrome Dependent on Parenteral Support.

OBJECTIVES: Our objective was to evaluate the short- and long-term safety and efficacy of teduglutide treatment in infants and children with short bowel syndrome with intestinal failure (SBS-IF). METHODS: Two open-label phase 3 studies and 1 extension study investigated the short- and long-term safety and efficacy of teduglutide (0.05 mg/kg/day) in infants and children with SBS-IF: NCT03571516, 24-week study of infants who were randomized to receive teduglutide or standard of care (SoC); NCT02980666, 24-week study of infants and children who all received teduglutide; and NCT03268811, 24-week extension study of patients who completed NCT02980666 (patients could receive up to 48 weeks of total treatment). RESULTS: Twelve infants and 8 children enrolled in the core studies, and 2 infants and 7 children in the extension study. After 24 weeks of treatment, parenteral support (PS) requirements reduced by ≥20% from baseline for 4 infants (57.1%) and 4 children (66.7%) receiving teduglutide and for 2 infants receiving SoC (50.0%). One infant (50.0%) and 4 children (80.0%) receiving teduglutide maintained the ≥20% reduction in PS at 48 weeks of treatment. Two children receiving teduglutide achieved enteral autonomy, after 12 weeks and 28 weeks of treatment, respectively. All adverse events (AEs) were in line with known impacts of SBS-IF and adverse reactions to teduglutide. Only one serious AE (abdominal pain) was considered related to teduglutide. CONCLUSIONS: Short- and long-term treatment with teduglutide resulted in clinically meaningful reductions in PS requirements for infants and children with SBS-IF. Teduglutide was well tolerated, and efficacy improved with longer-term treatment.

Safety Findings in Pediatric Patients During Long-Term Treatment With Teduglutide for Short-Bowel Syndrome-Associated Intestinal Failure: Pooled Analysis of 4 Clinical Studies.

BACKGROUND: This analysis assessed combined safety data from 4 clinical studies of teduglutide in pediatric patients with short-bowel syndrome-associated intestinal failure (SBS-IF). METHODS: Safety data from teduglutide-treated patients in 4 clinical trials were pooled. The completed 12-week and 24-week phase 3 core studies (NCT01952080/EudraCT 2013-004588-30 and NCT02682381/EudraCT 2015-002252-27) enrolled children aged 1-17 years with SBS-IF. Patients could elect to enroll in ongoing open-label extensions (NCT02949362/EudraCT 2016-000863-17 and NCT02954458/EudraCT 2016-000849-30). Interim data from ongoing studies were included. RESULTS: Safety data are reported for 89 pediatric patients treated with teduglutide for a median (range) of 51.7 (5.0-94.7) weeks. Adverse events (AEs) were reported in all patients; the most common were vomiting (51.7%), pyrexia (43.8%), upper respiratory tract infection (41.6%), and cough (33.7%). Thirty-five patients (39.3%) had AEs considered related to teduglutide treatment; abdominal pain and vomiting were most frequent (5.6% each). Three serious AEs in 3 patients (3.4%) were considered related to teduglutide treatment: ileus, d-lactic acidosis, and gastrointestinal obstruction due to hard stools. All 3 events resolved. One cecal polyp was detected, which was not biopsied or found on repeat colonoscopy. No cases of neoplasia occurred. CONCLUSION: Based on integrated data from 4 clinical studies, including long-term follow-up for ≤161 weeks, teduglutide had a safety profile consistent with the individual core pediatric studies and as expected for pediatric patients with SBS-IF who never received teduglutide. The most frequent AEs reflected treatment with teduglutide, complications of the underlying disease, and typical childhood illnesses.

Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome: A 24-Week, Phase III Study.

BACKGROUND: This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome-associated intestinal failure (SBS-IF). METHODS: A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a ≥20% reduction in parenteral support (PS) from baseline at week 24. RESULTS: All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P < 0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P < 0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3%, 0.025 mg/kg teduglutide) and 3 patients (11.5%, 0.05 mg/kg teduglutide) achieved enteral autonomy. CONCLUSION: The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.

Social circumstances and medical complications in children with intestinal failure.

UNLABELLED: Although most children discharged on home parenteral nutrition (HPN) will achieve enteral autonomy, some remain parenteral nutrition dependent; those who develop life-threatening complications may undergo small bowel transplantation (SBTx). The aim of this study was to investigate the relationship between social circumstances, compliance and complications. SUBJECTS AND METHODS: An observational study in 2008-2012 on 64 children (34 HPN, 30 SBTx) from three units (two regional gastroenterology; one transplant). Social circumstances were assessed routinely as part of discharge planning; adherence by families to home care management was scored, and episodes of catheter-related blood stream infection and graft rejection were recorded for 2 years and related to compliance and social circumstances. RESULTS: A quarter of families had a disadvantaged parent: non-English speaking (n=11), unable to read (n=5), physical disability (n=3), mental health problems disclosed (n=10); 20% children were cared for by a lone parent. Discharge home was delayed by social factors (n=9) and need for rehousing (n=17, 27%). 17/34 (50%) of HPN and 12/30 (40%) of transplant families were assessed as fully adherent. 10 families were assessed as non-adherent, eight were subject to child protection review and care was taken over by another family member (n=3) or foster parents (n=2). The risk of catheter-related blood stream infection was increased by parental disadvantage and age <3 years (p<0.05). Poor compliance was associated with complications in HPN and SBTx recipients. CONCLUSIONS: Children receiving complex home care may be socially isolated and measures to support improved compliance such as increased community support, social care involvement and respite care may improve outcomes.

Symposium 6: Young people, artificial nutrition and transitional care. Transition in young people on home parenteral nutrition.

Pharmacological, surgical and technological advances have resulted in children now surviving through adolescence into adulthood with conditions that were previously unseen by adult services. Arranging transition for young people on home parenteral nutrition (HPN) to the adult sector is one of greatest challenges for health services that care for young people. Transition is not only a key quality issue for health services, but is a multidimensional process covering psychosocial, educational and vocational aspects. Poorly-planned transition may result in difficulties when young people access adult specialist services. As a consequence, there may be increased risk of non-adherence or lack of follow-up, which carries dangers of morbidity and mortality as well as poor social and educational outcomes. Transition does not end at the exit from the paediatric clinic, but continues into the adult sector, which needs to provide developmentally-appropriate clinical care. Recent Department of Health initiatives are aimed at ensuring that young people do not miss out on healthcare during the transfer between paediatric and adult services. Transfer can be a major, often daunting, event for young people. Parents may also fear transfer and need to learn to 'let go' of some control, which may be particularly difficult with a young person on HPN.

Gastrointestinal symptoms in children with type 1 diabetes screened for celiac disease.

BACKGROUND: The association between celiac disease (CD) and type 1 diabetes mellitus (DM) is recognized. Most cases of CD in patients with DM are reported to be asymptomatic. OBJECTIVES: The objectives of this study were to (1) compare and audit our practice with the published standards for screening for CD in children with DM, (2) characterize the children with DM and biopsy-confirmed CD, in terms of growth and gastrointestinal symptoms, and compare them with children with DM and negative celiac serology, and (3) document the effects of a gluten-free diet (GFD) after 1 year of gastrointestinal symptoms, growth, and insulin requirement. METHOD: We performed a retrospective case-note review of 22 children with DM, positive celiac serology +/- biopsy-confirmed CD, and 50 children with DM and negative celiac serology. RESULTS: Twenty-two children (3.9% of the total diabetic population) had positive celiac serology on screening, with 17 (3%) having biopsy-confirmed CD. Ninety-four percent of the children had standardized celiac serology testing. At diagnosis of CD, 13 of the 17 biopsy-positive children (76.4%) had > or =1 gastrointestinal symptom. The frequency of gastrointestinal symptoms in negative celiac serology diabetic children was 6% (3 of 50) (P < .0005). Symptoms resolved in all children after introduction of a GFD. A significant improvement in weight SD score (P = .008) and BMI SD score (P = .02) was noted in those compliant with a GFD after 1 year. CONCLUSIONS: Children with DM and CD have a higher frequency of gastrointestinal symptoms than their diabetic peers with negative celiac serology and are not truly asymptomatic. Institution of a GFD has a positive effect on nutritional status and symptom resolution in the short-term.