Use Of Teduglutide Research Articles

Management Patterns of Teduglutide Use in Short Bowel Syndrome: A Survey of 70 Healthcare Professionals.

This study aimed to gain real-world insights from healthcare professionals (HCPs) regarding the management of adult patients with short bowel syndrome and intestinal failure (SBS-IF) who received teduglutide and achieved parenteral support (PS) independence or PS volume stability for ≥12 months. This cross-sectional survey was conducted in five European countries and Canada via a self-reported questionnaire (November 2022-March 2023) among HCPs who manage patients with SBS-IF and who had prescribed teduglutide to ≥5 patients with SBS-IF receiving PS. Of the 70 HCPs who completed the survey, almost all reported managing patients with SBS-IF who achieved PS independence or PS volume stability (99%, 69/70 and 97%, 68/70, respectively) and maintained the standard teduglutide dose, without changes. A total of 52 HCPs managed patients who achieved PS independence and discontinued teduglutide. Of these HCPs, 73% (38/52) anticipated that these patients would remain PS-independent, not requiring PS reintroduction. Of the remainder, 79% (11/14) estimated that ≤40% of these patients would require PS reintroduction. While many HCPs (81%, 42/52) would reintroduce teduglutide in patients who discontinued its use after achieving PS independence, none would do so for patients who discontinued teduglutide after achieving PS volume stability if a patient's condition worsened. This survey found that patients with SBS-IF can achieve PS independence or PS volume stability with teduglutide treatment. However, some HCPs (27%, 14/52) believe that a proportion of patients discontinuing teduglutide after achieving PS independence will require PS reintroduction. This survey suggests that teduglutide treatment should continue uninterrupted, unless clinically indicated, but this requires confirmation in future studies.

Pancreatitis Associated With Teduglutide: A Disproportionality Analysis via the Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

Introduction Teduglutide is a glucagon-like peptide-2 analog that is indicated for the treatment of short bowel syndrome (SBS) by reducing patient dependence on parenteral support. Due to the rarity of SBS as well as the recent timeline of the adoption of teduglutide, the safety of teduglutide is relatively poorly understood. Several recent clinical case reports have highlighted elevated pancreatic enzymes and pancreatitis as a concerning complication of teduglutide. This prompts a systematic study of the association between pancreatitis and teduglutide. Methods This study conducts a case-control design disproportionality analysis by using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). Reports from the first quarter of 2020 through the first quarter of 2024 were retrieved from this database, and a disproportionality analysis was conducted. The analysis consisted of traditional methods of analyzing adverse drug events such as the reporting odds ratio (ROR) and proportional reporting ratio (PRR), as well as Bayesian methods such as the empirical Bayes geometric mean (EBGM) and information component (IC). A confidence interval for ROR and PRR that excludes a ratio of 1 or a confidence interval for IC that excludes a score of 0 was used as the criterion for a statistically significant association between pancreatitis risk and teduglutide use. Results Out of 11,696 reports of teduglutide adverse effects in over four years of adverse effects data drawn from the FAERS database, 79 cases of pancreatitis were identified. The disproportionality analysis revealed an ROR of 3.73 (95% CI (2.99, 4.66)), a PRR of 3.71 (95% CI (2.97, 4.63)), an EBGM of 3.70, and an IC of 1.84 (95% CI (1.51, 2.16)). All of these statistics indicate a statistically significant association between pancreatitis risk and teduglutide use. Conclusion The results reveal a statistically significant association between pancreatitis risk and teduglutide use. Our findings highlight the necessity for the careful monitoring of pancreatitis in patients undergoing teduglutide therapy going forward.

Intestinal adaptation and rehabilitation in adults with short bowel syndrome.

Over the past decade, trophic gastrointestinal hormonal factors have been included in the intestinal rehabilitation programs for short bowel syndrome (SBS). Up today the only trophic factor approved for clinical practice is the glucagon-like peptide-2 (GLP-2) analogue, teduglutide. A literature review on the last 2-year data on GLP-2 analogues for the treatment of SBS in adults has been performed. Several reports on real-world data on the efficacy and safety of teduglutide treatment for SBS, some case-reports on the use of teduglutide in non-SBS conditions as well as phase 2 trials on new GL-2 analogues on patients with SBS have been retrieved. Real-world data confirmed the teduglutide efficacy not only in weaning off IVS in accurately selected patients but also increased the alert on the risk of development of gastrointestinal polyps related to the drug; the impact of the therapy on patients' QoL deserves further studies and the cost-utility of the treatment is still uncertain. Some case reports highlighted the potential benefit of treatment with teduglutide in non-SBS gastrointestinal diseases, such as graft-versus-host disease, primary amyloidosis and refractory microscopic colitis. Phase 2 RCTs on safety and efficacy of two new long-acting GLP-2 analogues, glepaglutide and apraglutide, were published, and phase 3 RCTs have been completed.

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 5years in Spain. This was a national multicentre and prospective study of paediatric patients with intestinal failure (IF) treated with teduglutide for at least 3months. 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 > 1year and 9 treated for > 3years. 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.

Evaluation of the Effectiveness of Teduglutide Treatment in Patients with Short Bowel Syndrome in Slovakia-Multicenter Real-World Study.

(1) Background: We present the first real-world-data study on teduglutide-treated SBS patients in the Slovak Republic and the first study to enable the comparison of the effects of teduglutide treatment between the adult and pediatric populations. (2) Methods: This was a non-interventional retrospective cohort study of adult and pediatric SBS patients treated with teduglutide. Primary and secondary endpoints were the results of teduglutide use at 12 weeks and 6 months after the initiation of treatment, compared to baseline. (3) Results: Teduglutide treatment led to a statistically significant reduction in the volume of intravenous hydration, HPN caloric intake, HPN and intravenous hydration applications per week and to increased urine output in adult patients. The results in the pediatric population were similar, but not statistically significant. A complete weaning off HPN was achieved in 57.14% of all patients (50.00% of children; 62.50% of adults) after a median of 0.99 years of teduglutide treatment (1.07 and 0.98 years for children and adults, respectively). (4) Conclusions: Teduglutide treatment in SBS patients leads to considerable reduction in or even weaning off PN in both pediatric and adult patients.

Use of Teduglutide in the Management of Gastrointestinal Graft-versus-Host Disease in Children and Young Adults

Loss of intestinal L cells and reduced levels of glucagon-like peptide-2 (GLP-2) have been implicated in acute graft-versus-host disease (GVHD) in murine models. Teduglutide, a human recombinant GLP-2 analog, may be beneficial in acute gastrointestinal (GI) GVHD owing to its known tissue protective and regenerative functions. We retrospectively reviewed patients who received teduglutide for treatment of GI GVHD. Endoscopy was performed at diagnosis and at completion of the teduglutide course. GLP-1 immunohistochemistry (IHC) was performed at diagnosis and the end of teduglutide therapy in 2 patients to evaluate L cells. We initiated daily teduglutide 0.05 mg/kg subcutaneously as adjunctive therapy in 3 pediatric patients with refractory GI GVHD. All 3 patients had resolution of GI GVHD following completion of the teduglutide course, as evidenced by reduced apoptosis and regenerative changes on post-treatment endoscopy. Reportable GLP-1 IHC in 2 patients demonstrated increased L cells at the end of teduglutide treatment compared to at diagnosis. No adverse effects to teduglutide were observed. Teduglutide is a promising adjunctive and non-immune suppressive agent for managing acute GI GVHD.

Successful Use of Teduglutide As Adjunctive Therapy in the Management of GI GvHD in Children and Young Adults: A Single Center Case Series.

Successful Use of Teduglutide As Adjunctive Therapy in the Management of GI GvHD in Children and Young Adults: A Single Center Case Series.

S136 Use of Teduglutide in a Patient With Ulcerative Colitis and Short Bowel Syndrome: Case Report

S136 Use of Teduglutide in a Patient With Ulcerative Colitis and Short Bowel Syndrome: Case Report

Post-market use of teduglutide (TED) in a large cohort of adults with short bowel syndrome (SBS)

Post-market use of teduglutide (TED) in a large cohort of adults with short bowel syndrome (SBS)

SAT028 Beneficial Effect On Intestinal Growth Of A Long-Acting GLP-2 Analog, HM15912, After Treatment Switching From Conventional GLP-2 Drug Or Other Long-Acting GLP-2 Analogs Under Clinical Development In Animal Model

Abstract Disclosure: C. Park: Employee; Self; Hanmi Pharm. Co., Ltd. J. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. E. Park: Employee; Self; Hanmi Pharm. Co., Ltd. H. Kwon: Employee; Self; Hanmi Pharm. Co., Ltd. S. Bae: Employee; Self; Hanmi Pharm. Co., Ltd. D. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. Y. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. The widespread use of teduglutide, which is only approved GLP-2 analog drug for short bowel syndrome (SBS), may be still limited due to insufficient efficacy and leading to a significant burden for patients by daily administration. Hence, several long-acting GLP-2 analog drugs targeting once a week are currently in clinical development. Here, we investigated that HM15912, a novel long-acting GLP-2 analog, enabled to achieve additional small bowel trophic effect after switching from those existing GLP-2 analogs. To investigate additional intestinotrophic efficacy after switching from teduglutide to HM15912, C57BL/6 mice treated with twice daily administration of teduglutide for 2 weeks were switched to once-weekly administration of HM15912, or continued the typical treatment of teduglutide for the remaining 2 weeks. HM15912 treatment significantly increased wet weight of SI (72.9% over vehicle) compared to teduglutide treated group (39.4% over vehicle) after 2 weeks. After 2 more weeks treatment, while showing the maintained the increased SI weight in teduglutide treated group (58.3% at week 3 and 41.1% at week 4 over vehicle), SI weight was further increased after switching to HM15912 (61.2% at week 3 and 68.5% at week 4 over vehicle). Next, we synthesized GLP-2 analogs to have same sequences with glepaglutide and apraglutide. SD rats treated with every other day administration of these long acting GLP-2 analogs for 2 weeks were switched to HM15912 or continued the typical treatment of them for the remaining 2 weeks. HM15912 treatment significantly increased wet weight of SI compared to weekly GLP-2 analog drug treated groups after 2 weeks (84.4% versus 41.5% or 26.6% over vehicle). After 2 more weeks treatment, while showing the slight increment in SI weight in the long-acting GLP-2 analogs (50.5% and 37.4% over vehicle), SI weight was further increased after switching to HM15912 (82.1% and 90.7% over vehicle, respectively). In line with these results, D-xylose absorption capacity was also significantly increased after switching from existing GLP-2 analogs to HM15912. As a results, HM15912 significantly promoted small intestinal growth than existing GLP-2 analogs even with a less frequent dosing interval of once a week in rodents. A phase 2 clinical study of once-monthly dosing in patients with SBS is ongoing to evaluate the clinical relevance of these findings. Presentation: Saturday, June 17, 2023

S1146 Improved Outcomes Associated With Teduglutide Use in Patients With Both Short Bowel Syndrome and Crohn's Disease

S1146 Improved Outcomes Associated With Teduglutide Use in Patients With Both Short Bowel Syndrome and Crohn's Disease

The assessment of the effectiveness and safety of teduglutide in the treatment of children with chronic intestinal insufficiency. A systematic review

Chronic intestinal failure is a pathogenetic component in children with short bowel syndrome. Short bowel syndrome limits the patient's capacity to socialize fully, the bad prognosis of the child's physical and spiritual development, and the patient's family's organizational and material issues. The severity of the problem is aggravated by the limited prospects for surgical treatment of patients, including transplantology, the imperfection of the legal framework for health care, particularly in terms of parenteral nutrition at home, and the supply of expensive drugs, consumables, and equipment to children with short bowel syndrome under state guarantees. Developing an equivalent of glucagon-like peptide-2 (GLP-2), a drug teduglutide representing the endogenous intestinal growth factor and intestinal adaptation, created an additional therapeutic possibility for individuals with short bowel syndrome. There are no data in Russian academic literature on the efficacy and safety of teduglutide in pediatric practice.
 This study aims to conduct a systematic search and critical analysis of publications on the effectiveness and safety of using teduglutide in children with short bowel syndrome.
 Publications from the PubMed, Scopus, and eLibrary databases, as well as scientific journals, were examined from 2012 to 2022. The articles were reviewed in English and Russian. Seven hundred seventy publications on using teduglutide in experimental and clinical practice were found; 94 sources matched the keywords; and eight articles were selected according to the PRISMA criteria. The risks of confounding bias were assessed using the ROBINS-I tool. Most patients received the therapeutic impact of teduglutide, and 8.4%64.7% of patients achieved enteral autonomy. The drug's dose was 0.05 mg/kg/day. Without a therapeutic effect, the time limits for the inappropriate use of teduglutide ranged from 6 months to 1 yr. There is no causal relationship between taking teduglutide and undesirable reactions to treatment. The review of publications revealed an insufficient evidence foundation for the efficacy of teduglutide due to a lack of control groups in most studies, a small sample size, and errors in data methodology. Despite the encouraging preliminary results of individual studies, the problem of a shortage of randomized controlled tests of teduglutide remains.

The indications and results of the use of teduglutide in patients with short bowel.

Short bowel syndrome (SBS) is a rare condition defined as a reduced residual functional small intestinal length to less than 200 cm often resulting from extensive intestinal resection, and can lead to chronic intestinal failure (CIF). Patients with SBS-CIF are unable to absorb sufficient nutrients or fluids to maintain metabolic homeostasis through oral or enteral intake and require long-term parenteral nutrition and/or fluids and electrolytes. However, complications may arise from both SBS-IF and life-sustaining intravenous support, such as intestinal failure-associated liver disease (IFALD), chronic renal failure, metabolic bone disease and catheter-related complications. An interdisciplinary approach is required to optimize intestinal adaptation and decrease complications. In the last two decades, glucagon-like peptide 2 (GLP-2) analogs have sparked pharmacological interest as a potential disease-modifying therapy for SBS-IF. Teduglutide (TED) is the first developed and marketed GLP-2 analog for SBS-IF. It is approved in the United States, Europe, and Japan for use in adults and children with SBS-IF who are intravenous supplementation dependent. This article discusses the indications, candidacy criteria and results of the use of TED in patients with SBS.

118: The Use of Teduglutide in Intestinal Transplantation: A Case Series

118: The Use of Teduglutide in Intestinal Transplantation: A Case Series

90: Use of teduglutide during breast-feeding after pregnancy in a patient with severe intestinal failure

90: Use of teduglutide during breast-feeding after pregnancy in a patient with severe intestinal failure

Use of teduglutide in adults with short bowel syndrome-associated intestinal failure.

Short bowel syndrome (SBS) is a rare gastrointestinal disorder associated with intestinal failure (SBS-IF) and poor health-related outcomes. Patients with SBS-IF are unable to absorb sufficient nutrients or fluids to maintain significantly metabolic homeostasis via oral or enteral intake alone and require long-term intravenous supplementation (IVS), consisting of partial or total parenteral nutrition, fluids, electrolytes, or a combination of these. The goal of medical and surgical treatment for patients with SBS-IF is to maximize intestinal remnant absorptive capacity so that the need for IVS support may eventually be reduced or eliminated. Daily subcutaneous administration of the glucagon-like peptide 2 analog, teduglutide, has been shown to be clinically effective in reducing IVS dependence and potentially improving the health-related quality of life of patients with SBS-IF. The management of patients with SBS-IF is complex and requires close monitoring. This narrative review discusses the use of teduglutide for patients with SBS-IF in clinical practice. The screening of patient eligibility for teduglutide treatment, initiation, monitoring of efficacy and safety of treatment, adapting or weaning off IVS, and the healthcare setting needed for SBS-IF management are described, taking into consideration data from clinical trials, observational studies, and clinical experience.

Post-Marketing Use of Teduglutide in a Large Cohort of Adults with Short Bowel Syndrome-Associated Chronic Intestinal Failure: Evolution and Outcomes.

Teduglutide, a GLP-2 analogue, has been available in France since 2015 to treat short-bowel-syndrome (SBS)-associated chronic intestinal failure (CIF) but it remains very expensive. No real-life data on the number of potential candidates are available. The aim of this real-life study was to assess teduglutide initiation and outcomes in SBS-CIF patients. All SBS-CIF patients cared for in an expert home parenteral support (PS) center between 2015 and 2020 were retrospectively included. Patients were divided into two subpopulations: prevalent patients, already cared for in the center before 2015, and incident patients, whose follow-up started between 2015 and 2020. A total of 331 SBS-CIF patients were included in the study (156 prevalent and 175 incident patients). Teduglutide was initiated in 56 patients (16.9% of the cohort); in 27.9% of prevalent patients and in 8.0% of incident patients, with a mean annual rate of 4.3% and 2.5%, respectively. Teduglutide allowed a reduction in the PS volume by 60% (IQR: 40-100), with a significantly higher reduction in incident versus prevalent patients (p = 0.02). The two- and five-year treatment retention rates were 82% and 64%. Among untreated patients, 50 (18.2%) were considered ineligible for teduglutide for non-medical reasons. More than 25% of prevalent SBS patients were treated with teduglutide compared to 8% of incident patients. The treatment retention rate was >80% at 2 years, which could be explained by a careful selection of patients. Furthermore, this real-life study confirmed the long-term efficacy of teduglutide and showed a better response to teduglutide in incident patients, suggesting a benefit in early treatment.

Successful experience in the use of teduglutide in children with short bowel syndrome

The article presents an overview of current trends in the approach to the treatment of patients with short bowel syndrome (SBS), including the example of pediatric patients in the Tyumen region. SBC is an extremely rare nosological form in the practice of a clinician and, as a rule, patients with such a diagnosis require a multidisciplinary approach. The most common manifestations of the disease are symptoms of malabsorption: dumping syndrome, progressive weight loss, deficiency of macro- and micronutrients, other manifestations of dyspepsia and abdominal pain. Attention is drawn to the fact that the number and intensity of symptoms varies significantly among patients. The traditional tactic for treating such patients includes the need for lifelong parenteral nutrition or, as a necessary measure, intestinal transplantation. Rehabilitation measures in SBS children should take into account the requirements for correcting impaired absorption and restoring normal trophic status; relief of diarrhea, prevention and treatment of dysbiosis; control and correction of general digestive disorders. We found that the analogue of glucagon-like peptide 2 (GLP-2) - teduglutide - makes it possible to reduce the amount of parenteral nutrition, infusion time, and also achieve a complete transition to enteral autonomy. The method of treatment with Teduglutide is the most promising for patients of this category.

Tracking the physicochemical stability of teduglutide (Revestive®) clinical solutions over time in different storage containers

Teduglutide, the active ingredient of the medicine Revestive® (5 mg), is a recombinant therapeutic peptide that mimics the effects of the endogenous glucagon-like peptide 2 (GLP-2). It stimulates intestinal growth, adaptation and function in patients with Short Bowel Syndrome who are dependent on parenteral nutrition. The Summary of Product Characteristics recommends immediate use of the reconstituted solutions and the discarding of any subsequent surplus. This study aims to carry out a long-term stability study that reproduces hospital conditions of use which provide sound evidence regarding the use of teduglutide surplus beyond the Summary Product Characteristics recommendations. We conducted a stability study of teduglutide solutions prepared from a 5 mg vial of Revestive®. Some of the solutions were stored in their original vial after reconstitution, while others were repackaged in plastic syringes to evaluate their physicochemical stability over time. For this purpose, we applied a set of previously validated analytical methodologies to evaluate the main critical quality attributes of teduglutide, i.e., primary (including post-tralational modifications), secondary and tertiary structures, aggregates, particulate, concentration and pH. The results indicate that the solutions maintain high physicochemical stability over time, regardless of the storage temperature (4ºC or −20ºC) or the storage container (vials or syringes). This research provides new data on the stability of Revestive® that will be of great value to hospital pharmacists. This comprehensive assessment of the physicochemical long-term stability of TGT has demonstrated that under the storage conditions and over the period studied here, the medicine maintains its quality, efficacy and safety profiles.

Teduglutide for the treatment of low-output enterocutaneous fistula - A pilot randomized controlled study.

Enterocutaneous fistula (ECF) is a complication of surgery or inflammatory bowel disease associated with disproportionately high healthcare costs, morbidity, and mortality. We performed this proof-of-concept, feasibility, open-label, pilot randomized, crossover study to assess the efficacy and safety of the use of teduglutide (TED) to treat ECF. Adults (age >18) with low-output (<200mL/d) ECF were randomized to 2 months of continuing standard-of-care (SOC) followed by crossover to 2 months of SOC+TED or the reverse order. The primary efficacy endpoint was decrease in fistula volume by 20% of baseline 3-day average. Secondary efficacy endpoints were: fistula resolution and health-related quality of life questionnaire scores. Six out of 10 planned subjects were randomized and completed the study, which was terminated early due to slow enrollment during the Covid-19 pandemic. Overall subject compliance with daily TED injections was high (98%). Five of six enrolled subjects met the definition for the primary efficacy endpoint; these clinical responses were not observed during the SOC arm in these subjects. One subject experienced complete fistula closure during TED treatment. Adverse events during treatment were uncommon, minor, and usually resolved despite ongoing treatment. Quality of life survey responses were highly variable and did not correlate with fistula changes. Two months of teduglutide treatment was feasible, well-tolerated, and resulted in observable decreases in ECF drainage in the majority of subjects, including spontaneous closure in one subject. This therapy shows promise, but larger, multicenter confirmatory trials are required. GOV: (NCT02889393).