Experience with teduglutide treatment for short bowel syndrome in clinical practice

Pevny, Sophie; Maasberg, Sebastian; Rieger, Anja; Karber, Mirjam; Blüthner, Elisabeth; Knappe-Drzikova, B.; Thürmann, D.; Büttner, Janine; Weylandt, Karsten H.; Wiedenmann, Bertram; Müller, Verena; Bläker, Hendrik; Pascher, Andreas; Pape, Ulrich‐Frank

doi:10.1016/j.clnu.2018.07.030

Cited by 50 publications

(81 citation statements)

References 51 publications

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“…In patients, Teduglutide reduces parenteral hydration requirements, likely through improved water and electrolyte absorption [37][38][39]. Recent indirect evidence points to positive effects on nutrient absorption as well because parenteral energy supplementation can be reduced without body composition changes under Teduglutide therapy [40].…”

Section: Discussionmentioning

confidence: 99%

“…While the trophic effects on the small intestinal mucosa by GLP-2 stimulation are well described [40][41][42][43], the functional relevance of small bowel villus growth is less clear. The mechanistic implication of villus growth is called into question by translational observations: 1) Villus growth in response to Teduglutide is not in the same order of magnitude as a reduction of parenteral support (PS) [13], and enterocyte mass expansion does not correlate with PS reduction [42].…”

Section: Discussionmentioning

confidence: 99%

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Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency

et al. 2020

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Background In short bowel syndrome, epithelial surface loss results in impaired nutrient absorption and may lead to intestinal insufficiency or intestinal failure. Nucleotide oligomerization domain 2 (Nod2) dysfunction predisposes to the development of intestinal failure after intestinal resection and is associated with intestinal barrier defects. Epithelial barrier function is crucial for intestinal absorption and for intestinal adaptation in the short bowel situation. Aims The aim of the study was to characterize the effects of the GLP-2 analogue Teduglutide in the small intestine in the presence and absence of Nod2 in a mouse model of short bowel syndrome. Methods Mice underwent 40% ICR and were thereafter treated with Teduglutide versus vehicle injections. Survival, body weight, stool water, and sodium content and plasma aldosterone concentrations were determined. Intestinal and kidney tissue was examined with light and fluorescence microscopy, Ussing chamber studies and quantitative PCR in wild type and transgenic mice. Results Teduglutide reduced intestinal failure incidence in Nod2 k.o. mice. In wt mice, Teduglutide attenuated intestinal insufficiency as indicated by reduced body weight loss and lower plasma aldosterone concentrations, lower stool water content, and lower stool sodium losses. Teduglutide treatment was associated with enhanced epithelial paracellular pore function and enhanced claudin-10 expression in tight junctions in the villus tips, where it colocalized with sodium-glucose cotransporter 1 (SGLT-1), which mediates Na-coupled glucose transport. Conclusions In the SBS situation, Teduglutide not only maximizes small intestinal mucosal hypertrophy but also partially restores small intestinal epithelial function through an altered distribution of claudin-10, facilitating sodium recirculation for Na-coupled glucose transport and water absorption. Keywords Short bowel syndrome • Mouse model • Ussing chamber • Teduglutide • Barrier function • Nucleotide oligomerization domain 2 Abbreviations GLP-2 Glucagon-like peptide 2 Nod2 Nucleotide oligomerization domain 2 RAAS Renin-angiotensin-aldosterone system PS Parenteral support

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency

et al. 2020

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“…Despite its ability to sustain life, PN may lead to life‐threatening complications and inevitably impacts patients’ quality of life (QoL) . Considerable advances in surgical technique and medical management—such as restoration of digestive tract continuity, intestinal transplantation, and the recent development of glucagon‐like peptide‐2 analogues for functional intestinal rehabilitation—have progressively increased survival rates and nutrition autonomy of patients with IF . As research and clinical care continue to progress within this period of disease‐specific treatment for patients with IF, it is essential not only to investigate the morbidity and mortality of these treatments but also to understand how they affect patients’ QoL.…”

Section: Introductionmentioning

confidence: 99%

Determinants of Quality of Life in Patients With Intestinal Failure Receiving Long‐Term Parenteral Nutrition Using the SF‐36 Questionnaire: A German Single‐Center Prospective Observational Study

Blüthner

Bednarsch

Stockmann

et al. 2019

J Parenter Enteral Nutr

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Background Parenteral nutrition (PN) is a life‐sustaining therapy for patients with chronic intestinal failure (IF) but inevitably has an impact on patients’ quality of life (QoL). The purpose of this study was to examine multiple aspects of QoL by utilizing the standardized Short Form 36 (SF‐36) health survey. Methods Between 2014 and 2017, a total of 90 adult patients with IF who were receiving PN were prospectively enrolled in an observational study. All subjects underwent nutrition status assessment, liver assessment, blood tests, and QoL assessment based on the SF‐36. Univariate and multivariable analyses were performed to identify determinants of 8 domains and 2 summary scales of the SF‐36. Results Analysis of the SF‐36 questionnaire data showed that QoL was significantly worse compared with the general German population across all categories. Multivariable analysis revealed that bioelectrical impedance analysis of phase angle (1/10 categories), stoma/fistula (4/10 categories), oral intake (4/10 categories), infusions per week (1/10 categories), duration of PN (1/10 categories), citrulline (4/10 categories), and hemoglobin levels (1/10 categories) are independent risk factors affecting QoL. Conclusion This study uses the largest cohort of IF patients assessed by the standardized SF‐36 questionnaire to comprehensively analyze QoL. Presence of oral intake, presence of ostomy, and citrulline levels were independently correlated with 4 of 10 categories of the SF‐36. These results indicate that to improve QoL for IF patients, clinical care should focus on addressing the social and emotional value of oral intake, educational interventions, early stoma closure, and application of new targeted therapies.

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“…Des Weiteren sind medikamentöse sowie ernährungsmedizinische Maßnah-men und in Einzelfällen spezifische KDS-Behandlung bspw. mit einem GLP-2-Analogon oder Transplantation zu nennen [21,22]. Ziel der ambulanten Versorgung ist es, Spätfolgen der Grunderkrankung und der lebenswichtigen Organersatztherapie zeitnah zu erkennen, entsprechend zu therapieren sowie Lebensqualität zu erhalten.…”

Section: Kostenberechnung Der Ambulanten Labormedizinischen Leistungunclassified

Interdisziplinäre Betreuung von Patienten mit Kurzdarmsyndrom in Deutschland: Eine Cost-of-Illness-Analyse der stationären und ambulanten Behandlung im Vergleich zum erzielten DRG-Erlös

et al. 2020

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Zusammenfassung Hintergrund und Fragestellung Das Kurzdarmsyndrom (KDS) ist eine oft chronische Erkrankung mit hoher Morbidität. Diese Untersuchung sollte Versorgungsrealität und -kosten bei der Behandlung von KDS aus Sicht eines Maximalversorgers mit angeschlossener Hochschulambulanz darstellen. Material und Methodik Es wurden Behandlungsdaten von elf konsekutiven KDS-Patienten am Universitätsklinikum Bonn über vier Jahre anonymisiert ausgewertet. Die ermittelten Leistungen wurden für das Diagnosejahr und drei folgende Behandlungsjahre entsprechend geltenden Leistungskatalogen monetär bewertet. Ergebnisse Die medianen stationären Tage reduzierten sich von 96 (Diagnosejahr) auf drei Tage im dritten Jahr. Dementsprechend sanken die medianen stationären Therapiekosten von rund 84 500 € auf 3200 €. Die operativen Maßnahmen verlagerten sich von komplexen viszeralchirurgischen Operationen zu meist gefäßchirurgischen Interventionen zur Aufrechterhaltung der venösen Zugangswege. Die DRG-Pauschalen deckten nur rund 50 % der tatsächlichen stationären Kosten. Die Hochschulambulanz-Pauschale deckte rund 16,5 % der ambulanten Leistung. Die jährlichen medianen Kosten für Arzneimittel betrugen 6752 €, für parenterale Ernährung 48 485 € und für die Therapie mit einem GLP-2-Analogon 138 442 €. Folgerung Die interdisziplinäre Versorgung von KDS-Patienten ist kosten- und ressourcenintensiv. Sie verlagert sich vom stationären in den ambulanten Sektor. Weder die stationäre noch die ambulante Behandlung ist zurzeit kostendeckend vergütet. Dies führt zu fortbestehenden Mängeln der Patientenversorgung in Zeiten ökonomischer Rationalisierung, sodass von der Notwendigkeit zusätzlicher Maßnahmen analog zur sektorenübergreifenden Versorgungsverbesserung bei anderen seltenen Erkrankungen auszugehen ist.

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Experience with teduglutide treatment for short bowel syndrome in clinical practice

Cited by 50 publications

References 51 publications

Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency

Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency

Determinants of Quality of Life in Patients With Intestinal Failure Receiving Long‐Term Parenteral Nutrition Using the SF‐36 Questionnaire: A German Single‐Center Prospective Observational Study

Interdisziplinäre Betreuung von Patienten mit Kurzdarmsyndrom in Deutschland: Eine Cost-of-Illness-Analyse der stationären und ambulanten Behandlung im Vergleich zum erzielten DRG-Erlös

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