Teduglutide 5mg powder and solvent for solution for injection vials

BackgroundPediatric short bowel syndrome (SBS) poses management challenges, and teduglutide is a potential therapy. However, comprehensive data on its pediatric safety are lacking.AimTo evaluate the impact of teduglutide on infection and gastrointestinal adverse events in pediatric SBS patients via systematic review and meta-analysis.MethodsFollowing PRISMA 2009 guidelines and PROSPERO registration, we searched PubMed, Web of Science, and EMBASE for randomized controlled trials (RCTs) (pediatric SBS patients ≤ 18 years; teduglutide vs placebo/standard care). Two reviewers screened studies, extracted data, and assessed bias (ROB2). Meta-analyses used RevMan 5.4 (Mantel-Haenszel method, random-effects if I 2 ≠ 0). Trial sequential analysis and GRADE were applied.ResultsThree RCTs involving 115 pediatric patients were included. Pooled analysis revealed no statistically significant differences between the teduglutide and control groups for the primary outcome of infection events [RR = 0.83; (95%CI: 0.44-1.56); P = 0.57; I 2 = 0%; 2 studies, n = 55]. Similarly, no significant differences were found for secondary outcomes: Upper respiratory tract infection [RR = 0.68; (95%CI: 0.32-1.47); P = 0.33; I 2 = 0%], catheter site infection [RR = 1.86; (95%CI: 0.23-14.78); P = 0.56; I 2 = 0%], vomiting [RR = 1.35; (95%CI: 0.10-18.23); P = 0.82; I 2 = 72%], abdominal pain [RR = 2.47; (95%CI: 0.50-12.16); P = 0.27; I 2 = 0%], nausea [RR = 1.31; (95%CI: 0.24-7.22); P = 0.75; I 2 = 0%], diarrhea [RR = 1.02; (95%CI: 0.23-4.43); P = 0.98; I 2 = 0%], and abdominal distension [RR = 1.49; (95%CI: 0.18-12.35); P = 0.71; I 2 = 0%]. The overall certainty of evidence assessed by GRADE was moderate.ConclusionTeduglutide does not increase infection or gastrointestinal adverse event risk in pediatric SBS, but small sample sizes limit conclusions. Larger studies are needed.

Abstract licence: CC BY-NC

Abstract Background Although studies have evaluated the safety and efficacy of GLP drugs in adult patients with short bowel syndrome, pediatric applications remain contentious due to developmental divergences in drug response and safety profiles. This meta-analysis aims at systematically evaluating efficacy and safety outcomes of teduglutide in pediatric SBS and providing comprehensive evidence for clinical practitioners and families of affected children. Methods and analysis: Randomized controlled trials (RCTs) and cohort studies comparing teduglutide and placebo or regular treatments in pediatric patients with a confirmed diagnosis of short bowel syndrome will be included. Literature searches will be conducted in PubMed, Web of Science, Embase, and Cochrane Library. Two reviewers independently perform the processes of literature retrieval, screening, data extraction, and assessment of risk of bias. Risk of bias in included studies is evaluated using Revised Cochrane risk-of-bias tool (ROB 2) for RCTs and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-1) for non-RCTs. Review Manager (RevMan) was used for data pooling. Subgroup analysis, meta-regression, trial sequential analysis (TSA), and sensitivity analysis are conducted. Ethics and dissemination: Ethical approval is not required because this study is a secondary analysis of existing data. We will disseminate the findings through peer- reviewed publications. PROSPERO registration number: CRD420251047221

Abstract licence: CC BY

Background and ObjectivesShort-bowel syndrome (SBS) results from the loss of a significant portion of the small intestine leading to a state of malabsorption. After an intestinal loss, there is a process of adaptation involving the Glucagon-Like Peptide-2 (GLP-2), an enteroendocrine peptide also involved in nutrient absorption. Teduglutide is a recombinant analog of GLP-2 approved in 2016 to treat selected SBS pediatric patients who are dependent on parenteral support. The present systematic review aims to evaluate the efficacy of Teduglutide in pediatric patients with SBS in reducing the need for parenteral nutrition (PN).Materials and MethodsWe performed a literature search on MEDLINE and Embase to include articles up to November 2021. We included articles that involved using Teduglutide in the SBS pediatric population to define its efficacy in reducing the need for PN. The key words used were GLP-2, teduglutide, child.ResultsFourteen studies completely fulfilled the inclusion criteria. Two hundred 23 patients were treated with Teduglutide, and the median duration of treatment was 45 weeks (IQR: 36–52.5 weeks). One-hundred and fifty-two patients were treated with 0.05 mg/Kg/d of subcutaneous Teduglutide, 38 received 0.025 mg/Kg/d and 8 received either 0.125 mg/Kg/d or 0.20 mg/Kg/d. A total of 36 patients achieved enteral autonomy (EA) after a median of 24 weeks of treatment (IQR: 24–48 weeks) and 149 patients showed a reduction in PN needs in terms of volume, calories, or hours per day. Eleven studies reported complications: gastrointestinal were the most common, with 89 cases reported in treated patients and 11 in non-treated patients.ConclusionTeduglutide appears safe and effective in reducing PN requirements and improving EA in the pediatric population. However, more studies are needed to understand its efficacy in the long term and after discontinuation and possible complications.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022301593].

Abstract licence: CC BY 4.0