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)

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.

Treatment of short bowel syndrome: Breaking the therapeutic ceiling?

Short bowel syndrome (SBS) is the most common cause of chronic intestinal failure, requiring home parenteral support (intravenous fluid, parenteral nutrition, or parenteral nutrition with intravenous fluid) to compensate for severe malabsorption. The loss of mucosal absorptive area after extensive intestinal resection is accompanied by an accelerated transit and hypersecretion. Changes in physiology and clinical outcomes differ between patients with SBS with or without the distal ileum and/or colon-in-continuity. This narrative review summarizes the treatments used in SBS, with a focus on novel approaches with intestinotrophic agents. During the early postoperative years, spontaneous adaptation occurs and can be induced or accelerated with conventional therapies, which include dietary and fluid modifications and antidiarrheal and antisecretory drugs. Based on the proadaptive role of enterohormones (eg, glucagon-like peptide [GLP]-2), analogues have been developed to allow enhanced or hyperadaptation after a period of stabilization. Teduglutide is the first GLP-2 analogue developed and commercialized with proadaptive effects resulting in reduced parenteral support needs; however, the potential for weaning of parenteral support is variable. Whether early treatment with enterohormones or accelerated hyperadaptation would further improve absorption and outcomes remains to be shown. Longer-acting GLP-2 analogues are currently being investigated. Encouraging reports with GLP-1 agonists require confirmation in randomized trials, and dual GLP-1 and GLP-2 analogues have yet to be clinically investigated. Future studies will prove whether the timing and/or combinations of different enterohormones will be able to break the ceiling of intestinal rehabilitation in SBS.

Pathophysiology of gastrointestinal acute graft-versus-host disease and the potential role of glucagon-like peptide 2.

Acute graft-versus-host disease (aGVHD) is a life-threatening complication after allogeneic haematopoietic cell transplantation, with gastrointestinal (GI) tract involvement (GI aGVHD) being one of the leading causes of morbidity and mortality. Whilst systemic steroids are the standard first-line treatment for aGVHD, approximately 50% of patients become steroid refractory (SR), which is associated with poor outcomes. Existing options for SR-GVHD are limited, and there is a significant unmet need for new non-immunosuppressive treatment approaches in patients with GI aGVHD. Here, we review newer concepts in the pathogenesis of GI aGVHD and present the evidence for the role of glucagon-like peptide 2 (GLP-2) in maintaining and protecting GI epithelial cells, including the enterocytes, intestinal stem cells and Paneth cells, which are direct targets of aGVHD. Finally, we discuss the therapeutic rationale for GLP-2 treatment as a tissue regeneration approach and the potential use of the novel GLP-2 analogue apraglutide as an adjunctive treatment for GI aGVHD.

Comprehensive physicochemical characterization of a peptide-based medicine: Teduglutide (Revestive®) structural description and stress testing.

Teduglutide (Revestive®) is a glucagon-like peptide-2 analogue used for the treatment of short bowel syndrome, a rare life-threatening condition in which the amount of functional gut is too short to enable proper absorption of nutrients and fluids. During handling prior to administration to the patient in hospital, it is possible that peptide-based medicines may be exposed to environmental stress conditions that could affect their quality. It is therefore essential to carry out stress testing studies to evaluate how such medicines respond to these stresses. For this reason, in this paper we present a strategy for a comprehensive analytical characterization of a peptide and a stress testing study in which it was subjected to various stress conditions: heating at 40 °C and 60 °C, light exposure and shaking. Several complementary analytical techniques were used throughout this study: Far UV circular dichroism, intrinsic protein fluorescence spectroscopy, dynamic light scattering, size-exclusion chromatography and intact and peptide mapping reverse-phase chromatography coupled to mass spectrometry. To the best of our knowledge, this is the first study to offer an in-depth description of the chemical structure of teduglutide peptide and its physicochemical characteristics after stress stimuli were applied to the reconstituted medicine Revestive®.

[Progress in intestinal adaptation after enterectomy].

Intestinal adaptation is a spontaneous compensation of the remanent bowel after extensive enterectomy, which improves the absorption capacity of the remanent bowel to energy, fluid and other nutrients. Intestinal adaptation mainly occurs within 2 years after enterectomy, including morphological changes, hyperfunction and hyperphagia. Intestinal adaptation is the key factor for patients with short bowel syndrome to weaning off parenteral nutrition dependence and mainly influenced by length of remanent bowel, type of surgery and colon continuity. In addition, multiple factors including enteral feeding, glucagon-like peptide 2 (GLP-2), growth hormone, gut microbiota and its metabolites regulate intestinal adaptation via multi-biological pathways, such as proliferation and differentiation of stem cell, apoptosis, angiogenesis, nutrients transport related protein expression, gut endocrine etc. Phase III clinical trials have verified the safety and efficacy of teduglutide (long-acting GLP-2) and somatropin (recombinant human growth hormone) in improving intestinal adaptation, and both have been approved for clinical use. We aim to review the current knowledge about characteristics, mechanism, evaluation methods, key factors, clinical strategies of intestinal adaptation.

Glucagon-like peptide-2 analogues for Crohn's disease patients with short bowel syndrome and intestinal failure.

Short bowel syndrome (SBS) with intestinal failure (IF) is a rare but severe complication of Crohn's disease (CD), which is the most frequent benign condition that leads to SBS after repeated surgical resections, even in the era of biologics and small molecules. Glucagon-like peptide-2 analogues have been deeply studied recently for the treatment of SBS-IF. These drugs have a significant intestinotrophic effect and the potential to reduce the chronic dependence of SBS-IF patients on parenteral support or nutrition. Teduglutide has been approved for the treatment of SBS-IF, and apraglutide is currently in clinical development. The use of these drugs was examined with a focus on their use in CD patients.

Method for identification and quantification of intact teduglutide peptide using (RP)UHPLC-UV-(HESI/ORBITRAP)MS.

Teduglutide (Revestive®, 10 mg mL-1) is a recombinant human glucagon-like peptide 2 analogue, used in the treatment of short bowel syndrome, a serious and highly disabling condition which results from either too small a length of intestine or loss of critical intestinal function. The determination of therapeutic compounds of protein-nature is always challenging due to their complex structure. In this work, we present a fast, straightforward reversed phase (RP)UHPLC-UV-(HESI/ORBITRAP)MS method for the identification and quantification of the intact teduglutide peptide. The method has been developed and validated in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines; therefore, linearity, limits of detection and quantification, accuracy (precision and trueness), robustness, system suitability and specificity using the signal from the UV and MS, have been evaluated. The validation performance parameters obtained from the UV and MS signals were compared throughout the work, to select the most suitable. To study the specificity of the method and the impact of medicine mishandling under hospital conditions, force degradation studies were performed, i.e. thermal (40 °C and 60 °C), shaking (mechanical) and light (accelerated exposition) effects. Identification by the exact mass of teduglutide was achieved and it was confirmed that the peptide does not undergo any post-translational modifications (PTMs). To the best of our knowledge, the present work reports the first method developed for the simultaneous identification, structural characterization, and quantification of the therapeutic teduglutide peptide. Finally, the proposed method is able to indicate stability when quantifying the intact teduglutide since detects and characterises the exact mass of the degradation/modification products.

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.

Therapeutic Potential of GLP-2 Analogs in Gastrointestinal Disorders: Current Knowledge, Nutritional Aspects, and Future Perspectives.

PURPOSE OF REVIEW: Although Glucagon-like peptide (GLP)-1 receptor agonists have been used for almost two decades in the treatment of diabetes mellitus type 2 and, lately, in obesity, recent years have seen an increasing interest in the pharmacological agonism of other proglucagon-derived peptides, including GLP-2. Herein, we aimed to review the available evidence on the effects of GLP-2 agonism from animal and clinical studies. Furthermore, we summarize the current clinical applications of GLP-2 agonists among patients with intestinal failure associated with short bowel syndrome (SBS-IF) as well as potential future expansion of their indications to other intestinal disorders. RECENT FINDINGS: Evidence from preclinical studies has highlighted the cellular trophic and functional beneficial actions of GLP-2 on small intestinal and colonic mucosa. Subsequently, pharmacologic agonism of GLP-2 has gathered interest for the treatment of patients with conditions pertaining to the loss of intestinal anatomical and/or functional integrity to a degree requiring parenteral support, collectively referred to as intestinal failure. GLP-2 analogs positively influence nutrient absorption in animal models and humans, although continued therapy is likely needed for sustained effects. The degradation-resistant GLP-2-analog teduglutide has received approval for the treatment of SBS-IF, in which it may decisively reduce patient dependency on parenteral support and improve quality of life. Another two longer-acting analogs, glepaglutide and apraglutide, are currently undergoing phase III clinical trials. The use of GLP-2 analogs is effective in the management of SBS-IF and may show promise in the treatment of other severe gastrointestinal disorders associated with loss of effective intestinal resorptive surface area.

Teduglutide in pediatric intestinal failure: A position statement of the Italian society of pediatric gastroenterology, hepatology and nutrition (SIGENP).

In recent years, the spectrum of possible treatments for Intestinal Failure (IF)-Short Bowel Syndrome (SBS) has been enriched by the implementation of GLP-2 analogues. In Italy, teduglutide (Ted), an analogue of GLP-2, was approved in January 2021 by the Italian Regulatory Agency for Drugs (AIFA) for IF-SBS patients ≥1 year old. According to the Agency indications, Ted can now be prescribed by regional reference centers, with costs fully charged to the National Health Service. Following pediatric-use approval in our country and in light of scarce evidence in childhood, the pediatric network for IF of the Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) planned to share management methods of Ted in pediatric IF. The main purpose was to identify the best candidates from a cost-effective perspective. Thus, focusing on available literature and on expert opinions, the present position statement provides consensus-based recommendations on the use of Ted for pediatric gastroenterologists and nutritionists treating children with SBS.

An updated overview of glucagon-like peptide-2 analog trophic therapy for short bowel syndrome in adults.

Short bowel syndrome (SBS) is a clinical condition characterized by a failure to achieve optimal intestinal adaptation, which is necessary to maintain oral/enteral autonomy. At present, the treatment options for SBS are primarily intestinal replacement and rehabilitation. Intestinal rehabilitation mainly includes non-transplantation surgery and intestinal rehabilitation measures. In recent years, intestinal rehabilitation in patients with SBS using nutritional intestinal hormones, especially glucagon-like peptide-2 analogs, has made great progress. Many high-quality studies have provided evidence-based medical findings to support the development of clinical guidelines. This article reviews the latest research advancements regarding the use of glucagon-like peptide-2 analogs (teduglutide, glepaglutide, and apraglutide) in the treatment of SBS.

Enterohormone therapy for short bowel syndrome.

PURPOSE OF REVIEW: Short bowel syndrome (SBS) patients are at risk to develop intestinal failure when the decreased absorption of macronutrients, water, and electrolytes necessitates parenteral support for survival. The adverse effects of SBS and parenteral support negatively affect the quality of life (QoL) of SBS-intestinal failure patients. However, spontaneous intestinal adaptation along with disease-modifying therapies allow reducing parenteral support, thereby improving QoL. RECENT FINDINGS: During the first years following extensive surgery, spontaneous structural and functional intestinal changes take place which stimulate a more efficient nutrient and fluid absorption in the remaining bowel. Given their potential role in the ileal braking mechanism, enterohormones, such as glucagon-like peptide (GLP)-2, GLP-1, and peptide YY (PYY), promote an accelerated adaptation or hyperadaptation. While the exact role of GLP-1 and PYY in SBS is still being explored, GLP-2 analogs have clearly shown to be effective in improving outcome in SBS. SUMMARY: Whereas spontaneous intestinal adaptation improves the nutritional status of SBS patients to a certain extent, GLP-2 analogs can further decrease parenteral support needs through hyperadaptation. There are, however, other promising candidates on the horizon that - alone or in combination - could possibly establish additional disease-modifying effects.

Complementary and antagonistic effects of combined glucagon-like peptide-2 and glucagon-like peptide-1 receptor agonist administration on parameters relevant to short bowel syndrome.

BACKGROUND: Short bowel syndrome (SBS) is characterized by malabsorption requiring parenteral nutrition. The intestinotrophic glucagon-like peptide (GLP)-2 receptor agonist, h[Gly2]GLP2, is used to treat patients with SBS. Evidence suggests that GLP-1 receptor agonists such as exendin-4 (Ex4) may be beneficial in SBS given their ability to increase intestinal growth and delay gastric emptying (GE). METHODS: Intestinal growth, body weight (BW), food intake (FI), GE, gastrointestinal (GI) transit, intestinal permeability, and glucose tolerance were investigated in male and female C57/BL6 mice following vehicle, h[Gly2]GLP2, or Ex4 treatment, alone or in combination at "low," "medium," and "high" doses (0.1, 0.5, 1.0 and 0.01, 0.05, 0.1 µg/g, respectively). RESULTS: Only the h[Gly2]GLP2 low/Ex4 high-dose combination additively increased small intestinal (SI) weight compared with vehicle and both monoagonists (P < 0.01-0.001), via increased villus height (P < 0.01) and SI length (P < 0.05). This combination had no effects on BW; FI; and fat, liver, spleen, heart, and kidney weights but reduced GI transit (P < 0.001) versus low-dose h[Gly2]GLP2 monotreatment and abrogated the inhibitory effects of high-dose Ex4 on GE (P < 0.01) and of low-dose h[Gly2]GLP2 on intestinal permeability (P < 0.05). Ex4-induced improvements in glucose homeostasis were maintained upon combination with h[Gly2]GLP2 (P < 0.001). CONCLUSIONS: These findings suggest that combining specific doses of GLP-2- and GLP-1 receptor agonists additively improves SI growth and GI transit without detrimental effects on BW, FI, GE, and glucose homeostasis, and may be useful for the treatment of patients with SBS.

An overview of the current management of short-bowel syndrome in pediatric patients.

Short-bowel syndrome (SBS) is defined as a state of malabsorption after resection or loss of a major portion of the bowel due to congenital or acquired factors. This article presents an overview on the recent management of pediatric SBS. The pediatric SBS population is very heterogeneous. The incidence of SBS is estimated to be 24.5 per 100,000 live births. The nutritional, medical, and surgical therapies available require a comprehensive evaluation. Thus, multidisciplinary intestinal rehabilitation programs (IRPs) are necessary for the management of these complex patients. The key points of focus in IRP management are hepato-protective strategies to minimize intestinal failure-associated liver disease; the aggressive prevention of catheter-related bloodstream infections; strategic nutritional supply to optimize the absorption of enteral calories; and the management and prevention of small bowel bacterial overgrowth, nephrocalcinosis, and metabolic bone disease. As the survival rate of children with SBS currently exceeds 90%, the application of small bowel transplantation has been evolving. The introduction of innovative treatments, such as combined therapy of intestinotrophic hormones, including glucagon-like peptide-2, may lead to further improvements in patients' quality of life.

Apraglutide, a novel glucagon-like peptide-2 analog, improves fluid absorption in patients with short bowel syndrome intestinal failure: Findings from a placebo-controlled, randomized phase 2 trial.

BACKGROUND: Treatment with glucagon-like peptide-2 (GLP-2) analogs improve intestinal adaptation in patients with short bowel syndrome-associated intestinal failure (SBS-IF) and may reduce parenteral support requirements. Apraglutide is a novel, long-acting GLP-2 analog designed for once-weekly dosing. This trial investigated the safety and efficacy of apraglutide in patients with SBS-IF. METHODS: In this placebo-controlled, double-blind, randomized, crossover phase 2 trial, eight adults with SBS-IF were treated with once-weekly 5-mg apraglutide doses and placebo for 4 weeks, followed by once-weekly 10-mg apraglutide doses for 4 weeks, with a washout period of 6-10 weeks between treatments. Safety was the primary end point. Secondary end points included changes from baseline in urine volume output compared with placebo, collected for 48 h before and after each treatment period. RESULTS: Common treatment-related adverse events (AEs) were mild to moderate and included polyuria, decreased stoma output, stoma complications, decreased thirst, and edema. No serious AEs were considered to be related to apraglutide treatment. The safety profile was comparable for the lower and higher doses. Treatment with once-weekly 5- and 10-mg apraglutide doses significantly increased urine volume output by an adjusted mean of 714 ml/day (95% CI, 490-939; P < .05) and 795 ml/day (95% CI, 195-1394; P < .05), respectively, compared with placebo, with no significant differences between doses. CONCLUSIONS: Once-weekly apraglutide was well tolerated at both tested doses and significantly increased urine volume output, providing evidence for increased intestinal fluid absorption. A phase 3 trial is underway in adults with SBS-IF.

Progress in intestinal adaptation after enterectomy / 中华胃肠外科杂志

Intestinal adaptation is a spontaneous compensation of the remanent bowel after extensive enterectomy, which improves the absorption capacity of the remanent bowel to energy, fluid and other nutrients. Intestinal adaptation mainly occurs within 2 years after enterectomy, including morphological changes, hyperfunction and hyperphagia. Intestinal adaptation is the key factor for patients with short bowel syndrome to weaning off parenteral nutrition dependence and mainly influenced by length of remanent bowel, type of surgery and colon continuity. In addition, multiple factors including enteral feeding, glucagon-like peptide 2 (GLP-2), growth hormone, gut microbiota and its metabolites regulate intestinal adaptation via multi-biological pathways, such as proliferation and differentiation of stem cell, apoptosis, angiogenesis, nutrients transport related protein expression, gut endocrine etc. Phase III clinical trials have verified the safety and efficacy of teduglutide (long-acting GLP-2) and somatropin (recombinant human growth hormone) in improving intestinal adaptation, and both have been approved for clinical use. We aim to review the current knowledge about characteristics, mechanism, evaluation methods, key factors, clinical strategies of intestinal adaptation.

Rehabilitación del intestino utilizando un análogo semisintético del péptido 2 similar al glucagón. Primera experiencia con teduglutide en Uruguay / Intestinal rehabilitation using semisynthetic glucagon-like peptide-2 analogue. First experience with teduglutide in Uruguay / Reabilitação do intestino usando um análogo semi-sintético do peptídeo 2 semelhante ao glucagon. Primeira experiência com teduglutide no Uruguai

Resumen: La falla intestinal crónica (FIC) o tipo III es una condición invalidante, y la nutrición parenteral crónica (NPC) domiciliaria es el tratamiento que permite a estos pacientes mantenerse con vida. Sin embargo, solamente uno de cada tres países latinoamericanos cuentan con ese recurso, y sus complicaciones no son infrecuentes. Estas complicaciones son las principales indicaciones para trasplante intestinal, un procedimiento que en la mayoría de los países de ingresos medios no se ha desarrollado y no ha presentado los resultados esperados. En los últimos años, la rehabilitación intestinal a nivel mundial ha mejorado sustancialmente con el uso de análogos semisintéticos del péptido 2 similares al glucagón, existiendo cada vez mayor evidencia que demuestra la posibilidad de rehabilitación intestinal e independencia de la NPC con este fármaco, incluso en pacientes con anatomía desfavorable. Estos resultados han permitido mejorar la supervivencia y la calidad de vida de pacientes con FIC y, en muchas ocasiones, prescindir del trasplante. El paciente del caso que presentamos es el primero en recibir esta terapéutica en nuestro país. En este artículo analizamos la respuesta precoz favorable al tratamiento y sus perspectivas a futuro.

Abstract: Long-term home parenteral nutrition (HPN) is a life-saving treatment for patients with chronic intestinal failure, an invalidating condition. However, only 1 out of 3 countries can rely on this treatment and complications associated to chronic parenteral nutrition are rather frequent. The latter constitute the main indication for intestinal transplantion, a procedure that in most middle-income countries has not yet developed and has not shown the expected outcome. In recent years, intestinal rehabilitation has significantly improved at the global level with the use of GLP2, based on the growing evidence that proves the possibility of intestinal rehabilitation and independence from parenteral nutrition with Teduglutide, even in the case of patients with unfavorable anatomy. These results have caused a positive impact on survival and the quality of life of patients with chronic renal failure, and they can often abstain from transplant. The patient of the case study is the first one who received this therapy in our country and this article analyses his favorable early response to treatment and future perspectives.

Resumo: A insuficiência intestinal crônica (CIF) ou tipo III é uma condição incapacitante e a nutrição parenteral crônica (NPC) domiciliar é o tratamento que permite a sobrevida desses pacientes. No entanto, apenas 1 em cada 3 países latino-americanos dispõe desse recurso e as complicações da NPC não são raras. Essas complicações são as principais indicações para o transplante intestinal, procedimento que na maioria dos países de renda média não foi desenvolvido ou não apresentou os resultados esperados. Nos últimos anos, a reabilitação intestinal em todo o mundo tem melhorado substancialmente com o uso de sGLP2, com um número cada vez maior de evidências que mostram a possibilidade de reabilitação intestinal e independência da NPC, mesmo em pacientes com anatomia desfavorável. Esses resultados têm possibilitado prolongar a sobrevida e melhorar a qualidade de vida dos pacientes com CIF e, em muitos casos, dispensar o transplante. O paciente do caso que apresentamos é o primeiro a receber essa terapia em nosso país. Neste artigo, analisamos a resposta favorável ao tratamento precoce e suas perspectivas futuras.

Glucagon-like peptide 2 analogues in the treatment of intestinal failure: A qualitative exploration of the views of patients and their families in decision making.

BACKGROUND AND AIMS: Patients with short bowel syndrome and type 3 intestinal failure (SBS-IF) are dependent on parenteral nutrition (PN), a lifesaving treatment but inconvenient and with risks. Glucagon-like peptide 2 analogue (teduglutide) can reduce patients' need for PN. However, it comes with the risk of a number of side effects. This qualitative study investigated patients' decision making process to start teduglutide and how family members contributed to the decision. METHODS: In-depth semi-structured interviews were conducted with nine participants, six patients with SBS-IF and three family members about the decision to take teduglutide. Interviews were transcribed verbatim and analysed using framework analysis. RESULTS: The prominent motivation for taking teduglutide (Revestive® Takeda Pharmaceuticals Limited) was reducing or stopping PN. Other motivations were to help others by assisting in developing the knowledge base around teduglutide, patients felt that they had nothing to lose by trying the drug and the support of relatives. The reasons patients considered not taking the drug were that they had accepted being on PN, the potential side effects of teduglutide and undergoing extra monitoring. However, the monitoring programme also acted as a motivator providing reassurance that patients would be observed and supported with side effects. Family members were happy to support patients' decision to try teduglutide, although they had more reservations, indicating a higher risk threshold. CONCLUSION: Patients considered potential benefits of teduglutide outweighed any disadvantages. Relatives, although supportive, had more reservations.