Obeticholic acid attenuates the intestinal barrier disruption in a rat model of short bowel syndrome.

BACKGROUND: Short bowel syndrome (SBS) features nutrients malabsorption and impaired intestinal barrier. Patients with SBS are prone to sepsis, intestinal flora dysbiosis and intestinal failure associated liver disease. Protecting intestinal barrier and preventing complications are potential strategies for SBS treatment. This study aims to investigate the effects of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), have on intestinal barrier and ecological environment in SBS. METHODS AND RESULTS: Through testing the small intestine and serum samples of patients with SBS, impaired intestinal barrier was verified, as evidenced by reduced expressions of intestinal tight junction proteins (TJPs), increased levels of apoptosis and epithelial cell damage. The intestinal expressions of FXR and related downstream molecules were decreased in SBS patients. Then, global FXR activator OCA was used to further dissect the potential role of the FXR in a rat model of SBS. Low expressions of FXR-related molecules were observed on the small intestine of SBS rats, along with increased proinflammatory factors and damaged barrier function. Furthermore, SBS rats possessed significantly decreased body weight and elevated death rate. Supplementation with OCA mitigated the damaged intestinal barrier and increased proinflammatory factors in SBS rats, accompanied by activated FXR-related molecules. Using 16S rDNA sequencing, the regulatory role of OCA on gut microbiota in SBS rats was witnessed. LPS stimulation to Caco-2 cells induced apoptosis and overexpression of proinflammatory factors in vitro. OCA incubation of LPS-pretreated Caco-2 cells activated FXR-related molecules, increased the expressions of TJPs, ameliorated apoptosis and inhibited overexpression of proinflammatory factors. CONCLUSIONS: OCA supplementation could effectively ameliorate the intestinal barrier disruption and inhibit overexpression of proinflammatory factors in a rat model of SBS and LPS-pretreated Caco-2 cells. As a selective activator of FXR, OCA might realize its protective function through FXR activation.

Teduglutide improves liver chemistries in short bowel syndrome-associated intestinal failure: Post hoc analysis.

BACKGROUND: Chronic hepatic complications are common in patients with short bowel syndrome-associated intestinal failure (SBS-IF). Teduglutide, a glucagon-like peptide-2 analogue, demonstrated efficacy in reducing parenteral nutrition and/or intravenous fluid dependence among patients with SBS-IF in phase 3 clinical studies. METHODS: This was a post hoc analysis of pooled data from two separate randomized, double-blind, placebo-controlled, multinational phase 3 clinical studies. Adult patients with SBS-IF with parenteral nutrition and/or intravenous fluid dependence without liver disease at baseline were randomized to treatment with the glucagon-like peptide-2 analogue teduglutide (0.05 or 0.10 mg/kg/day) or placebo subcutaneously once daily for 24 weeks. Mixed-effects models assessed the baseline predictors of change in liver chemistries. RESULTS: Between baseline and week 24, teduglutide treatment (n = 109) was associated with least squares mean reductions in aspartate aminotransferase (-7.51 IU/L; P = 0.014), alanine aminotransferase (-12.15 IU/L; P = 0.002), and bilirubin (-5.03 µmol/L [-0.057 mg/dl]; P < 0.001) compared with that of the placebo (n = 59). These values were independent of reductions in parenteral nutrition and/or intravenous fluid dependence. CONCLUSION: Teduglutide treatment was associated with reductions in liver chemistries by week 24, which is beneficial for patients with SBS-IF beyond improvements in parenteral nutrition and/or intravenous fluid dependence. Future studies should examine how long-term teduglutide might mitigate the risk of liver disease in patients with SBS-IF.

Cost-effectiveness of teduglutide in adult patients with short bowel syndrome - a European socioeconomic perspective.

BACKGROUND: Short bowel syndrome with intestinal failure (SBS-IF) is a rare but devastating medical condition. An absolute loss of bowel length forces the patients into parenteral support dependency and a variety of medical sequelae, resulting in increased morbidity and mortality. Interdisciplinary treatment may include therapy with the effective but expensive intestinotrophic peptide teduglutide. OBJECTIVES: A time-discrete Markov model was developed to simulate the treatment effect [lifetime costs, quality-adjusted life years (QALYs), and life years (LYs)] of teduglutide plus best supportive care compared with best supportive care alone in patients with SBS-IF. METHODS: The health status of the model was structured around the number of days on PS. Clinical data from 3 data sets were used: 1) an Austrian observational study (base case), 2) pooled observational cohort studies, and 3) a prospective study of teduglutide effectiveness in parenteral nutrition-dependent short bowel syndrome subjects. Direct and indirect costs were derived from published sources. QALYs, LYs, and costs were discounted (3% per annum). RESULTS: Under the base case assumption, teduglutide is associated with costs of 2,296,311 € per patient and 10.78 QALYs (13.74 LYs) over a lifetime horizon. No teduglutide is associated with 1,236,816 € and 2.24 QALYs (8.57 LYs). The incremental cost-utility ratio (ICUR) amounts to 123,945 €. In case of the pooled clinical data set, the ICUR increases to 184,961 €. If clinical data based on the study of teduglutide effectiveness in parenteral nutrition-dependent short bowel syndrome subjects were used, the ICUR increased to 235,612 €. CONCLUSIONS: Teduglutide in treating patients with SBS-IF meets the traditional cost-effectiveness criteria from a European societal perspective. Nevertheless, the varying concentrations of teduglutide efficacy leave a degree of uncertainty in the calculations.

Long-term outcomes and adverse effects of teduglutide in patients with short bowel syndrome: Highlighting hyperamylasemia and hyperlipasemia.

PURPOSE: Short bowel syndrome is a malabsorptive condition that occurs due to surgical removal or a congenital absence of a significant portion of the small intestine. Patients with short bowel syndrome often rely on parenteral support for extended periods or even their entire lives. Teduglutide, a glucagon-like peptide-2 analog, has shown promising results in reducing dependency on parenteral support in these patients by promoting intestinal adaptation and enhancing nutrient absorption. However, the long-term safety of teduglutide remains a concern, particularly with respect to its potential for the development of hyperamylasemia and hyperlipasemia. METHODS: This study involved patients who received teduglutide from December 2012 to December 2022 at Boston Medical Center. We evaluated outcomes and adverse events, focusing on hyperamylasemia and hyperlipasemia, through chart review. RESULTS: Thirteen eligible patients were identified who had used teduglutide. Of these, the majority (84.6%) experienced a reduction in parenteral support. A high incidence (72.7%) of nonpathological pancreatic enzyme elevation was observed in patients treated with teduglutide. These elevations were often dose dependent and were not associated with any clinical signs of acute pancreatitis or abnormal imaging findings. CONCLUSION: This study highlights the need for further investigations into the long-term safety of teduglutide and the importance of closely monitoring amylase and lipase levels in patients undergoing treatment with teduglutide.

Therapeutic drug monitoring of osimertinib in non-small cell lung cancer and short bowel syndrome: A case report.

Short bowel syndrome (SBS) following extensive intestinal resection is often characterized by impaired absorption of orally administered drugs, including tyrosine kinase inhibitors (TKI). We report the case of a patient with EGFR-mutated non-small cell lung carcinoma treated with 80 mg/day of the TKI osimertinib who achieved partial response of the tumour, but was subsequently subjected to a double-barrelled jejunostomy due to ileus. Due to the development of SBS after the bypass surgery, plasma concentrations of osimertinib were monitored using mass spectrometry. The therapeutic drug monitoring confirmed a malabsorption of osimertinib in the patient (108 ng/mL, which is below the 5th percentile of the expected plasma concentration) and was useful to guide adjustments of TKI dosing in order to achieve adequate blood levels (161 ng/mL after increase of the dose to 120 mg/day) in order to maintain tumour control.

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.

Medication use in a cohort of adults with chronic intestinal failure: A prospective cross-sectional study.

BACKGROUND: Oral drug therapy may be compromised in chronic intestinal failure (IF) because of alterations in absorption and transit. Only scarce literature is available on which medication patients with chronic IF take in daily life. The aim was to describe the medication use in these patients. METHODS: A medication history was obtained from adults with chronic IF treated in our tertiary care IF center. Degree of polypharmacy, drug classes, Biopharmaceutics Classification System classes, route of administration, and formulation of drugs were analyzed. RESULTS: From October 2019 until December 2020, 72 patients (35 patients with short bowel syndrome [SBS] and 37 patients without SBS) were included. Polypharmacy was seen in 85.7% of patients with SBS and 75.7% of patients without SBS. The top three drug classes were proton-pump inhibitors, vitamin D or acetaminophen, and antimotility medication or laxatives/benzodiazepines. Approximately 25% of the drugs were classified as Biopharmaceutics Classification System class I drugs. In patients with SBS (78%) and patients without SBS (74.9%), most medication was taken orally, requiring gastrointestinal absorption of the active substance to be pharmacologically active. Most of these medications (77% in patients with SBS and 80.8% in patients without SBS) were formulated as a capsule or tablet, requiring disintegration and dissolution in the gastrointestinal tract before absorption can take place. CONCLUSION: Polypharmacy was observed in most patients with chronic IF. Most medication was taken orally in formulations requiring disintegration, dissolution, and gastrointestinal absorption, which could be compromised in chronic IF.

Effects of Teduglutide on Diarrhea in Pediatric Patients with Short Bowel Syndrome-Associated Intestinal Failure.

OBJECTIVES: This post-hoc analysis evaluated the effect of teduglutide treatment on diarrhea in patients with short bowel syndrome-associated intestinal failure (SBS-IF). METHODS: Data from 2 open-label, multicenter, phase 3 pediatric SBS-IF clinical trials of teduglutide (NCT01952080 and NCT02682381) were pooled where possible. The primary objective was to evaluate the change in stool consistency, frequency, and volume from baseline to weeks 12 and 24 of treatment in patients who received any teduglutide dose from both studies ("total teduglutide"). Safety assessments included gastrointestinal adverse event reporting. RESULTS: Overall, 101 patients were analyzed. Among the total teduglutide group (n = 87), there were significant changes from baseline to weeks 12 and 24 in mean (standard error) Bristol Stool Form Scale (BSFS) score [-1.8 (0.26; P < 0.0001) and -2.2 (0.27; P < 0.0001), respectively], parenteral nutrition and/or intravenous fluid (PN/IV) volume [-16.9 (1.7; P < 0.0001) and -20.1 (2.3; P < 0.0001) mL/kg/day, respectively], and enteral nutrition volume [9.2 (1.7; P < 0.0001) and 9.6 (2.3; P = 0.0002) mL/kg/day, respectively]. Among patients in the standard of care group (n = 14) there were numerical changes in BSFS score, and enteral nutrition volume at weeks 12 and 24; significant changes in PN/IV volume [-6.9 (1.5) mL/kg/day; P = 0.0041] were observed at 24 weeks, but not at 12 weeks. CONCLUSION: In this post-hoc analysis, short-term treatment with teduglutide was associated with improved stool consistency, as well as trends towards reductions in PN/IV requirements and advancements in enteral nutrition volume in children with SBS-IF. Further research assessing the impact of patient-level factors on stool characteristics when using teduglutide is warranted.

Cost-utility analysis of teduglutide compared to standard care in weaning parenteral nutrition support in children with short bowel syndrome.

BACKGROUND & AIMS: A growing proportion of children with short bowel syndrome (SBS) remain dependent on long-term parenteral nutrition (PN). Teduglutide offers the potential for more children to decrease PN support and achieve enteral autonomy (EA), but at a significant expense. This study aims to assess the incremental costs of teduglutide plus standard of care compared to standard of care alone in weaning PN support per quality-adjusted life year (QALY) gained in children with SBS. METHODS: This is a cost-utility analysis comparing teduglutide with standard of care alone in children with SBS. A microsimulation model of children with SBS on PN aged 1-17 years was constructed over a time horizon of six years, with a cycle length of one month. The study adopted the healthcare system and societal payer perspectives in Ontario, Canada. The health outcome measure was QALYs, with results expressed in terms of incremental costs and QALYs. Scenario analyses were performed to examine the effects of different time horizons, timing of teduglutide initiation, and modeling cost of teduglutide based on pediatric weight-dosing. RESULTS: Incremental healthcare system costs for teduglutide compared to standard of care were CAD$441,314 (95% CI, 414,006 to 441,314) and incremental QALYs were 1.80 (95% CI, 1.70 to 1.89) resulting in an incremental cost-effectiveness ratio (ICER) of CAD$285,334 (95% CI, 178,209 to 392,459) per QALY gained. Incremental societal costs were CAD$418,504 (95% CI, 409,487 to 427,522) and incremental societal QALYs were 1.91 (95% CI, 1.85 to 1.98) resulting in an ICER of CAD$261,880 (95% CI, 136,887 to 386,874) per QALY gained. Scenario analysis showed that teduglutide was cost-effective when it was started two years after intestinal resection (ICER CAD$48,741, 95% CI, 17,317 to 80,165) and when its monthly cost was adjusted using weight-based dosing, avoiding wastage of the remaining 5 mg dose vial (Teduglutide dominated over SOC as the less costly and most effective strategy). CONCLUSIONS: Although teduglutide was not cost-effective in weaning PN support in children with SBS, starting teduglutide once natural intestinal adaptation is reduced and adjusting its monthly cost to reflect cost by volume as dictated by weight-based dosing rendered the intervention cost-effective relative to standard of care. These results indicate the potential for clinicians to re-assess optimal time for initiation of teduglutide after intestinal resection, drug manufacturers to consider the use of multi-dose or paediatric-dose vials, and the opportunity for decision-makers to re-evaluate teduglutide funding.

Absorption of an engineered medium-chain fatty acid analogue in two short bowel syndrome minipig models.

BACKGROUND: Enteral drug therapy is challenging in short bowel syndrome with intestinal failure (SBS-IF) because of unpredictable absorption. SEFA-6179 is an enterally administered medium-chain fatty acid analogue under development for intestinal failure-associated liver disease. We investigate the pharmacokinetics of two SEFA-6179 formulations in two large-animal models of SBS-IF, including a new pseudojejunostomy model. METHODS: Twenty Yucatan minipigs were obtained. Half underwent pre-resection pharmacokinetic study with single-dose SEFA-6179 administration. All minipigs then underwent 90% jejunoileal resection, with either a jejunoileal anastomosis or bypass of the intraperitoneal colon with anastomosis just proximal to the rectum (pseudojejunostomy). On postoperative day 3, a single-dose pharmacokinetic study was performed. RESULTS: Both SBS-IF models were well tolerated. Compared with the jejunoileal anastomosis minipigs, pseudojejunostomy minipigs had a more severe malabsorptive phenotype with weight loss by postoperative day 4 (+0.1 vs -0.9 kg, P = 0.03) and liquid diarrhea (Bristol 5 vs Bristol 7, P = 0.0007). Compared with pre-resection minipigs, both jejunoileal and pseudojejunostomy minipigs had lower total plasma exposure of SEFA-6179 measured by area under the curve (jejunoileal: 37% less, P = 0.049; pseudojejunostomy: 74% less, P = 0.0001). Peak plasma concentration was also lower in the pseudojejunostomy group compared with pre-resection (65% less, P = 0.04), but not lower in the jejunoileal group (P = 0.47). CONCLUSION: In two SBS-IF minipig models, SEFA-6179 had substantially decreased absorption compared with pre-resection minipigs. Dose optimization for different intestinal anatomy and function may be required. We describe a new SBS-IF pseudojejunostomy model that may improve the translation of preclinical research to patients with SBS-IF who have enterostomies.

Revisión sobre la experiencia en vida real de teduglutida / Review of real-life teduglutide experience

Introducción: la teduglutida es un agonista del péptido relacionado con glucagón (aGLP2) eficaz como tratamiento de pacientes con síndrome de intestino corto (SIC) una entidad que afecta a la calidad de vida, suele precisar de nutrición parenteral domiciliaria (NPD) y genera importantes costes sanitarios. El objetivo de la presente revisión narrativa fue evaluar la experiencia en vida real reportada con teduglutida. Métodos y resultados: en vida real un metaanálisis y estudios publicados con 440 pacientes, indican que teduglutida es efectivo pasado el periodo de adaptación intestinal posterior a la cirugía, reduciendo las necesidades de NPD y en algunos casos permite incluso suspenderla. La respuesta es heterogénea, aumenta progresivamente hasta 2 años después del inicio del tratamiento y alcanza el 82 % en algunas series. La presencia de colon en continuidad es factor predictivo negativo de respuesta precoz, pero un factor predictivo positivo para la retirada de NPD. Los efectos adversos más frecuentes son de origen gastrointestinal en las primeras etapas del tratamiento. Hay complicaciones tardías relacionadas con el estoma o con la aparición de pólipos de colon, aunque la frecuencia de estas últimas es muy baja. En adultos son escasos los datos en mejoría de calidad de vida y en coste eficacia. Conclusiones: teduglutida es efectivo y seguro confirmándose en vida real los datos de los ensayos pivotales para tratamiento de pacientes con SIC y permite reducir o incluso suspender en algunos casos la NPD. Aunque parece coste efectivo son necesarios más estudios para identificar aquellos pacientes con mayor beneficio.(AU)

Background: teduglutide is an agonist of glucagon-related peptide (aGLP2) effective as a treatment for patients with short bowel syndrome (SBS), an entity that affects quality of life, usually requires home parenteral nutrition (HPN) and generates significant health costs. The objective of the present narrative review was to assess the real-life experience reported with teduglutide.Methods and results: in real life, one meta-analysis and studies published with 440 patients indicate that Teduglutide is effective after the period of intestinal adaptation after surgery, reducing the need for HPN and in some cases even allowing it to be suspended. The response is heterogeneous, increasing progressively up to 2 years after the start of treatment and reaching 82 % in some series. The presence of colon in continuity is a negative predictor of early response, but a positive predictive factor for the withdrawal of HPN. The most common side effects are gastrointestinal in the early stages of treatment. There are late complications related to the stoma or the occurrence of colon polyps, although the frequency of the latter is very low. In adults, data on improved quality of life and cost-effectiveness are scarce. Conclusions: teduglutide is effective and safe and data from pivotal trials for the treatment of patients with SBS are confirmed in real life and can reduce or even stop HPN in some cases. Although it seems cost-effective, more studies are needed to identify those patients with the greatest benefit.(AU)

[Review of real-life teduglutide experience]. / Revisión sobre la experiencia en vida real de teduglutida.

Introduction: Background: teduglutide is an agonist of glucagon-related peptide (aGLP2) effective as a treatment for patients with short bowel syndrome (SBS), an entity that affects quality of life, usually requires home parenteral nutrition (HPN) and generates significant health costs. The objective of the present narrative review was to assess the real-life experience reported with teduglutide. Methods and results: in real life, one meta-analysis and studies published with 440 patients indicate that Teduglutide is effective after the period of intestinal adaptation after surgery, reducing the need for HPN and in some cases even allowing it to be suspended. The response is heterogeneous, increasing progressively up to 2 years after the start of treatment and reaching 82 % in some series. The presence of colon in continuity is a negative predictor of early response, but a positive predictive factor for the withdrawal of HPN. The most common side effects are gastrointestinal in the early stages of treatment. There are late complications related to the stoma or the occurrence of colon polyps, although the frequency of the latter is very low. In adults, data on improved quality of life and cost-effectiveness are scarce. Conclusions: teduglutide is effective and safe and data from pivotal trials for the treatment of patients with SBS are confirmed in real life and can reduce or even stop HPN in some cases. Although it seems cost-effective, more studies are needed to identify those patients with the greatest benefit.

Introducción: Introducción: la teduglutida es un agonista del péptido relacionado con glucagón (aGLP2) eficaz como tratamiento de pacientes con síndrome de intestino corto (SIC) una entidad que afecta a la calidad de vida, suele precisar de nutrición parenteral domiciliaria (NPD) y genera importantes costes sanitarios. El objetivo de la presente revisión narrativa fue evaluar la experiencia en vida real reportada con teduglutida. Métodos y resultados: en vida real un metaanálisis y estudios publicados con 440 pacientes, indican que teduglutida es efectivo pasado el periodo de adaptación intestinal posterior a la cirugía, reduciendo las necesidades de NPD y en algunos casos permite incluso suspenderla. La respuesta es heterogénea, aumenta progresivamente hasta 2 años después del inicio del tratamiento y alcanza el 82 % en algunas series. La presencia de colon en continuidad es factor predictivo negativo de respuesta precoz, pero un factor predictivo positivo para la retirada de NPD. Los efectos adversos más frecuentes son de origen gastrointestinal en las primeras etapas del tratamiento. Hay complicaciones tardías relacionadas con el estoma o con la aparición de pólipos de colon, aunque la frecuencia de estas últimas es muy baja. En adultos son escasos los datos en mejoría de calidad de vida y en coste eficacia. Conclusiones: teduglutida es efectivo y seguro confirmándose en vida real los datos de los ensayos pivotales para tratamiento de pacientes con SIC y permite reducir o incluso suspender en algunos casos la NPD. Aunque parece coste efectivo son necesarios más estudios para identificar aquellos pacientes con mayor beneficio.

Nutritional management of a patient with chronic intestinal failure and hemodialysis receiving teduglutide: A case report.

We present the case of a 35-y-old woman with short bowel syndrome secondary to extensive intestinal resection with associated chronic kidney disease who was undergoing hemodialysis. This patient required permanent supplementation with intradialytic parenteral nutrition because of a high-output end-jejunostomy. The patient was a candidate for treatment with teduglutide, a glucagon-like peptide 2 analog, intending to increase intestinal absorption. A complete nutritional assessment was performed using bioelectrical impedance vector analysis. Teduglutide treatment was successful, and after a 1-y follow-up, the patient had considerably reduced end-jejunostomy output (reduction of 6 L/d) and an improved nutritional status (9.1 kg weight gain, 1.4 kg fat-free mass gain, and a 2.2-degree increase in bioimpedance phase angle). However, we have been unable to reduce intradialytic parenteral nutrition, which the patient requires thrice weekly. No significant secondary effects have occurred because of teduglutide administration. This may be the first reported use of teduglutide in a patient with short bowel syndrome undergoing hemodialysis who was monitored using bioelectrical impedance data during follow-up.

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.

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.

Unexpected upper gastrointestinal polyps in patients with short bowel syndrome treated with teduglutide: need for close monitoring.

BACKGROUND: Teduglutide is a GLP-2 analog indicated for the treatment of short bowel syndrome (SBS) since 2015. Its efficacy in reducing parenteral nutrition (PN) has been shown in patients with SBS. OBJECTIVES: Because teduglutide is a trophic factor, the aim of this study was to assess risk of developing polypoid intestinal lesions during treatment. METHODS: A retrospective study was conducted in 35 patients with SBS treated with teduglutide for ≥1 y in a home PN expert center. All patients underwent ≥1 follow-up intestinal endoscopy during treatment. RESULTS: In the 35 patients, the small bowel length was 74 cm (IQR: 25-100), and 23 patients (66%) had a colon in continuity. Upper and lower gastrointestinal endoscopy was performed after a mean treatment duration of 23 mo (IQR: 13-27), and polypoid lesions were found in 10 patients (6 with a colon in continuity, 4 with an end jejunostomy) and no lesion in 25 patients. In 8 out of the 10 patients, the lesion was found in the small bowel. Five of these lesions presented an aspect of hyperplastic polyp without dysplasia, and 3 of a traditional adenoma with low-grade dysplasia. CONCLUSIONS: Our study highlights the importance of performing follow-up upper and lower gastrointestinal endoscopy in SBS patients treated with teduglutide and the potential need to make changes to the recommendations with respect to treatment initiation and follow-up.

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.

Effects of Treatment with Liraglutide Early after Surgical Intervention on Clinical Outcomes in Patients with Short Bowel Syndrome: A Pilot Observational "Real-Life" Study.

Liraglutide, a glucagon-like peptide-1 agonist, has been shown to have beneficial effects on fecal output in short bowel syndrome (SBS) by small human studies. Its potential effects early after gut resection are not known. In this pilot observational study, we described the 1- and 6-month liraglutide effects in 19 adult patients with a new SBS diagnosis within 1 month after surgical resection. Stomal/fecal and urinary outcomes, serum/urinary electrolytes, and body composition were assessed. Both within-group differences and between-group comparisons with 20 SBS patients refusing liraglutide treatment were evaluated. The main liraglutide-related side effect was mild nausea, except in one patient, who experienced severe nausea/vomiting. The median ostomy/fecal output was significantly reduced by -550 mL/day after 6 months of treatment (vs. -200 mL/day in untreated, p = 0.04). The number of patients reaching a ≥20% output reduction was 10/19 (52.6%) treated vs. 3/20 (15.0%) untreated patients (p = 0.013) at 1 month and 12/19 (63.2%) vs. 6/20 (30.0%) (p = 0.038) at 6 months, respectively. Participants with a clinically relevant output reduction at 6 months had a significantly lower baseline weight and BMI. Energy parenteral supply significantly decreased, while infused volumes, oral energy, and fluid intakes slightly decreased, though not significantly. This pilot study supports liraglutide benefits in ostomy/fecal output early after surgical gut resection in SBS patients, particularly in those with lower baseline weight values.

Successful dasatinib therapy in newly diagnosed chronic myeloid leukemia in the setting of short bowel syndrome.

INTRODUCTION: There is limited guidance on the selection of tyrosine kinase inhibitors (TKIs) in patients with short bowel syndrome (SBS). Concerns regarding absorption, toxicity profiles, and drug interactions should be considered when selecting optimal TKI therapy. CASE REPORT: A 57-year-old male with SBS was newly diagnosed with chronic myeloid leukemia (CML). A careful review of his surgical history, comorbidities, and concurrent medications led to a treatment decision to initiate dasatinib at 100 mg once daily. MANAGEMENT AND OUTCOME: After initiation of therapy, the patient achieved a complete hematological response after two weeks and an early major molecular response on a three-month assessment. The therapy was tolerated well with no identified adverse effects. DISCUSSION: Clinical rationale for selecting dasatinib in patients with SBS includes supporting literature regarding its pharmacokinetic absorption characteristics, its efficacy with lower doses in newly diagnosed patients with CML, and its side effect profile in comparison to other second-generation TKIs. The case discussed provides an example of successful therapy in a patient with SBS undergoing treatment for CML.