1. Short Bowel Syndrome – novel therapies
Marek Kunecki
Centrum Leczenia Żywieniowego
WSS im M. Pirogowa Łódź

2. I have received honoraria, travel and accommodation funding from:
Shire Polska Sp. z o.o.
Nutricia Polska sp. z o.o.
Abbott Nutrition
Baxter Polska sp. z o.o.
Fresenius Kabi Polska sp. z o.o.
Diffuplast
BBraun
The views and opinions expressed in the following slides are those of the presenter. They should not be understood or quoted as being made on behalf of Shire.

3. Short bowel syndrome (SBS)
Diarrhea, dehydration, dyselectrolytemia, malnutrition, micronutrients deficites.
Result of massive bowel resection
loss of absorption surface of the bowel
loss of regulatory intestinal hormones.
Intestinal failure (IF) when adaptation is inadequate to meet the patient’s nutrient and/or fluid needs = parenteral support (PS) dependency
Catheter related complications
Long term organ disorders/failure
Complex of symptoms with predominant diarrea, and water/electrolyte disorders occuring after bowel resection exceeding ½ of the organ. The symptoms are result of loss of absorption area along with loss of regulatory hormones released in resected part of the bowel.
The term IF means loss of ability of maintaining water/electrolyte balanse and nutritional status with oral administration. Of course it also means dependency of PS, sometimes during lifetime, which is associated with several consequencies. NOT all of the patients with SBS develop IF!!!
Dudrick et al, Surg Clin North Am Jun;71(3): ; O’Keefe et al, Clin Gastroenterol Hepatol Jan;4(1):6-10.; Nightingale JMD et al., Gut, 1999 ,34, 1171, Scolapio et al. Mayo Clinic Proc 1999, 74, 217–222 ; Wilmore DWet al, Ann Surg 226:288–293

4. Survival in 124 SBS patients of non-cancer etiology
Survival probability [%]
Survival probability [%]
Years after resection
Years after resection
Survival probability [%]
Prognosis depends on underlying disease, remnant bowel lenght, and anatomy. The data reflect strong relation between degree of intestinal failure and life expectancy.
Messing B et al Gastroenterology 1999, 117, 1043–1050
Years after resection

5. Overall Treatment Goal for Patients with Short Bowel Syndrome
Optimize and manage fluid, electrolyte, and nutrient absorption at an individualized level
Maximize the digestive and absorptive capacity of the remnant gastrointestinal tract
Achieve a reduced need for parenteral nutrition and/or intravenous fluids
Generally the aim of treatment is to improve intestinal uptake of fluid, electrolytes, and nutrients. It results in diminishing of PS dependency
Seidner DL, et al. J Parenter Enteral Nutr. 2013;37(2):

6. Overall Treatment Goal for Patients with Short Bowel Syndrome
Minimize complications of SBS-IF:
cholelithiasis, kidney stones,
hypersecretion of gastric acid, D-lactic acidosis,
metabolic bone disease,
severe malabsorptive diarrhea with associated dehydration, electrolyte disturbances, weight loss, and malnutrition
Strive for an improvement in lifestyle and abatement of the risk of long-term complications of parenteral nutrition
Seidner DL, et al. J Parenter Enteral Nutr. 2013;37(2):

7. SBS/IF Treatment options
Standard treatment
Parenteral support (Life-supporting therapy)
Anti-diarrheal medication
Bowel rehabilitation
Novel therapies
However, three terapeutic options are possible in SBS patients. Combination of all of them is possible.
Bowel surgery
Intestinal transplantation
Presented data - property Dr M. Kunecki

8. Clinical course of SBS/IF (natural adaptation and treatment)
Minimal small bowel lenght:
Type I > 35 cm
Type II > 65cm
Type III > 150 cm
Bowel resection
Alimentary autonomy
Bowel function
Standard treatment:
Fluid and electrolyte management (prevent dehydration)
Macronutrients and dietary therapy (prevent malnutrition)
Micronutrients and trace metal supplementation (prevent nutrient deficiency)
Medical management of GI symptoms (eg H2 blockers or PPI to reduce fecal wet weight)
Parenteral support
Clinical observations shows that immediately after resection physiologic adaptation begins and the intestine becomes more efficient in nutrient absorption.
Unfortunatly it take couple of years until this process is completed. During this time some patients require PS as life supporting treatment. Along with PS patients receive complex therapy
Regaining of alimentary autonomy is possible in cases with appropriate lenght and anatomy od remnant bowel. The values of bowel lenght are provided at overall level. 1 2 3 4
M Kunecki
Time [years]
DiBaise JK et al. Am J Gastroenterol. 2004;99:1386–95; Jeppesen PB. J Nutr. 2003; 133:3721–4; Shaffer, J. Clin Nutr. 2002;21:144–145, Pironi L, et al. Clin. Nutr. 2016;35: ;Pironi L, et al Clin. Nutr. 2015;34:

9. Optimalized adaptation
Clinical course of SBS (potential effects of natural adaptation and treatment)
Bowel Tx, bowel elongation operations
Tissue engeneering(?)
Bowel resection
Optimalized adaptation
Trophic factors
Alimentary autonomy
Bowel function
P a r e n t e r a l s u p p o r t
In patients with insufficient bowel lenght, regaining of alimentary autonomy with natural adaptation processes is not possible. These patients remain PS dependent until the end of life.
This history might be changed by invasive intervention: bowel transplantation, which gives chance for spectacular improvement of alimentary system function. Serious disadvantage of this treatment is high perioperative mortality, shortage of organ donors, rejection reaction, and long term immunosuppression. Currently the number of all operations performed is about 100 per year
Bowel elongation operations in adult patients are possible in very small number of patients.
Currently emerging therapies are based on the knowledge on physiology of adaptation process and its hormonal regulation. The result of treatment might be described as optimalized adaptation.
Physiological adaptation + standard treatment 1 2 3 4
M Kunecki
Time [years]
DiBaise JK et al. Am J Gastroenterol. 2004;99:1386–95; Jeppesen PB. J Nutr. 2003; 133:3721–4; Shaffer, J. Clin Nutr. 2002;21:144–145; Pironi L, et al. Clin. Nutr. 2016;35: ; Pironi L, et al Clin. Nutr. 2015;34: ; Buchman, 1997 , Lloyd et al, 2006

10. Intestinal adaptation after resection
Rapid acceleration of crypt cell proliferation*
Crypt depth and villus height increase**.
Local angiogenesis, increased in tissue oxygenation and blood flow ***
Long-term adaptation following ileocecal resection in mice - extensive crypt fission including a trifurcated crypt#
*Loran MR, Crocker TT. J Cell Biol.1963;19: ; **Lauronen J, Pakarinen MP, Kuusanmaki P, et alScand J Gastroenterol. 1998;33: ; ***Rowland KJ, Yao J, Wang L, et al. J Pediatr Surg. 2012;47: ;# reprinted from: Christopher M. et al. Am. J Physiol - Gastrointest and Liver Physiol 2007 Vol. 293 no. 5, G1013-G1022

11. Intestinal adaptation after resection
Oral food intake is an important stimulus to intestinal adaptation1-3
Additional factors that influence time, course and extent of adaptation 1,2:
Underlying etiology
Post-operative course
Co-morbid conditions
Concomitant medications
Age at time of resection/injury
Adequate mesenteric blood flow
Length of remaining bowel
Health of remaining bowel
Presence or absence of ileocecal valve
Colon vs no colon
Ostomy vs no ostomy
Adaptation is induced by nutrients passing the lumen of the bowel. Oral feeding should be started soon after operation.
1) Buchman AL. Gastroenterology. 2003;124: ; 2) Weale AR, et al. Postgrad Med J ;81: ; 3) Crenn P, et al. Gut. 2004;53:

12. Factors stimulating bowel adaptation
Adaptation is regulated by hormones. The table shows active substances with proven influence on this process. In humans only 2 of them are well studied in terms of bowel adaptation process.
GH used to be tested as trophic factor in SBS patients, but it was not introduced to clinical practice because of weak and short term response.
Weale AR et al. Postgrad Med J 2005;81:178–184.

13. Glucagon-like peptide-2 (GLP-2)
Drucker DJ, et al. Proc Natl Acad Sci U S A. 1996;93(15):

14. GLP-2 Bone demineralisation Macronutrients absorption ** *
*Drucker DJ, Erlich P, Asa SL, et al. (1996) Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci USA 93:7911–7916.
**Wojdemann M, Wettergren A, Hartmann B, et al. (1998) Glucagon-like peptide-2 inhibits centrally induced antral motility in pigs. Scand J Gastroenterol 33:828–832

15. GLP-2
GLP-2 is a pleiotropic hormone, affecting multiple facets of intestinal physiology.
Foremost among these is the ability of GLP-2 to increase small and large intestinal weight through:
stimulation of epithelial cell proliferation and
inhibition of apoptosis,
leading to enlarged crypts and villi and, hence, an enhanced absorptive surface area.
Physiological role for GLP-2 appears to be the restoration of epithelial growth following periods of fasting.
GLP-2 also increases the capacity for carbohydrate, amino acid, and lipid absorption and increases the activity of epithelial brush-border digestive enzymes and nutrient transporters.
Shin ED, Estall JL, Izzo A, Drucker DJ, Brubaker PL. Mucosal adaptation to enteral nutrients is dependent on the physiologic actions of glucagon-like peptide-2 in mice. Gastroenterology 128: 1340–1353, 2005.

16. Proposed model for the indirect mechanisms of glucagon-like peptide-2 (GLP-2) action in the intestine.
Expression of the GLP-2R in intestinal endocrine cells (A), intestinal subepithelial myofibroblasts (SEMFs; B) and enteric neurons (C) suggests that GLP-2 acts indirectly to produce its diverse actions in the intestine.
Integrated model for control of crypt cell proliferation and differentiation.
Dubé PE, Brubaker PL, Am J Physiol Endocrinol Metab 2007;293:E460-E465
IGF-1=insulin-like growth factor 1; NO=nitric oxide ; VIP=vasoactive intestinal polypeptide

18. Temporal increase in small bowel weights in groups of 6-week-old female CD1 mice treated with vehicle alone (control) or
with synthetic GLP-2 (5 /.tg in PBS) twice a day, subcutaneously for 1, 2, 4, or 6 days (n = 5). **, P < 0.01.
Crypt plus villus heights in
proximal and distal jejunum and ileum fromA above, treated for 6 days
(n = 3). *, P < 0.05.

19. small intestine epithelium from control (a) and GLP-2-injected (10 days) (b) mice.

20. Improved Energy, Macronutrient Absorption1 Clinical Data
Statistically significant
∆=mean ± SD effect of treatment with GLP-2 compared with baseline;
Relative absorption of energy and macronutrients before and after 5 weeks of GLP-2 treatment in 8 patients with SBS
1.Jeppesen PB, et al. Gastroenterology. 2001;120:

21. Improved Wet Weight, Electrolyte Absorption1 Clinical Data
*Statistically significant;
∆= mean ± SD effect of treatment with GLP-2 compared with baseline
Relative absorption of wet weight, sodium, potassium, and calcium before and after 5 weeks of GLP-2 treatment in 8 patients with SBS
1.Jeppesen PB, et al. Gastroenterology. 2001;120(4):

22. Endogenous GLP-2 Increases Portal Blood Flow1 Preclinical Data75 1 2 3 4
Time of Infusion, hours
100
125
150
Portal Blood Flow, % Baseline (SEM)
GLP-2
Saline
Rapid increase for all time points beyond 10 minutes post infusion
Peak increase at 45 minutes; maintained plateau
Increased 25% compared with controls
*Study conducted in piglets
†P<0.01
Reprinted from 1. Guan X, et al. Gastroenterology. 2003;125(1): ;
Copyright 2003, with permission from Elsevier

23. Plasma glucagon-like peptide (GLP) 2 increment after meals A (300 ml Nutridrink) and (solid breakfast) in short bowel patients with a jejunostomy and sex and age matched controls. *p<0.05, **p<0.01, Mann-Whitney rank sum test.
Plasma glucagon-like peptide (GLP) 2 increment after meals A (300 ml Nutridrink) and (solid breakfast) in short bowel patients with a jejunostomy and sex and age matched controls. *p<0.05, **p<0.01, Mann-Whitney rank sum test.
P B Jeppesen et al. Gut 1999;45:

24. Teduglutide (Gly2-GLP-2)
Degradation by DPP – IV (dipeptydyl peptidase – 4) – - half – life time ~ 7 min.
Teduglutide (Gly2-GLP-2)
Presented data - property dr M Kunecki

25. Effect of teduglutide treatment on small intestine and colon
(A + B) In vivo stimulation Gly2-GLP-2. entrocyte and colonocyte mass
(C + D) mice jejunum: control group (C) and teduglutide (D)

26. Teduglutide effects: Phase 2 study results
According to the results of the study, compared with baseline (pooled groups), teduglutide increased wet weight absorption (P<0.001) and decreased faecal wet weight (P=0.001)
In SBS patients (n=17*) with end jejunostomy, teduglutide significantly increased
villus height (+38 (45)%; P=0.030),
crypt depth (+22 (18)%; P=0.010), and
mitotic index (+115 (108)%; P=0.010).
However, crypt depth and mitotic index did not change in colonic biopsies from SBS patients with colon in continuity.
*1 patient excluded from analysis after biopsy finding of remnant segment of colon
Jeppesen PB, et al. Gut. 2005;54(9):

27. Teduglutide effects: Phase 3 study Exploratory endpoints
Representative change in mucosa from baseline (A) to end of the study (B)
Samples obtained from a single patient in the 0.05 mg/kg/d teduglutide group
Tappenden KA, et al. J Clin Gastroenterol. 2013;47:

28. III phase clinical trials
004 (RCT)
005
(open label)
020 (RCT)
021
medication [mg/kg/d]
PBO
TED (0,05)
TED (0,1)
TED
(0,05/0,1)
(0,05)
Patient number 16 35 32 83 43 88
Mean age
48,8
50,3
Mean BMI
21,5
22,4
Bowel lenght[cm]
77±23
58±44
68±43
69±64
84±65
Colon in continuity 11 26 19 23
Time
24 weeks
28 weeks
2 years
Jeppesen PB, et al. Gut. 2011;60: ; Jeppesen PB, et al. Gastroenterology. 2012;143: ;
Schwartz LK et al. Clin. Transl. Gastroenterology 2016; 7, e142; doi: /ctg

29. Datum přípravy: říjen 2016 Zinc code: CZ/C-ANPROM/TED/16/0004

30. 20 (24) weeaks treatment (TED 0,05mg/kg/d, n=35)
Trials 004 i 005
20 (24) weeaks treatment (TED 0,05mg/kg/d, n=35)
52 weeks treatment (n = 25)
PN volume reduction
(baseline = 9,6 L/7d)
- 2,5 L/7d
- 4,9 L/7d (52%)
PN energy reduction
- 218 kcal/d
- 501 kcal/d
PN frequency reduction (≥ 1 inf/7d)
68% patients
Weaning off PN
2 patients
3 patients
Jeppesen PB i wsp. Gut 2011, 60,902-14

31. Phase 3- Study 004 Results - Safety
Teduglutide was well-tolerated throughout the 4-week study
Overall compliance was 85% in across all treatment groups
N, (%)
Teduglutide 0.05 mg/kg/day
(n=35)
Teduglutide
0.10 mg/kg/day (n=32)
Placebo
(n=16)
Subjects with AE
33 (94%)
31 (97%)
15 (94%)
Subjects with SAE
13 (37%)
11 (34%)
5 (31%)
Subjects with any AE or SAE leading to study discontinuation
6 (17%)
2* (6%)
1*(6%)
In 8 patients AE lead to study discontinuation.
It should be taken into consideration, that patients enrolled were sevely ill, on long term PN, with serious underlying disease.
*Serious AE. Coma, dysuegia, hypersomnia all found in one patient
Jeppesen PB et al. Gut. 2011;60:

32. Phase 3- Study 004 Results- Safety
Most common AEs occurring in teduglutide groups
Abdominal pain (24%)
Headache (24%)
Nausea (22%)
Nasopharyngitis (16%)
Vomiting (15%)
Most common serious AEs were catheter-related complications, catheter sepsis, catheter site infection, small intestinal obstruction, and fever
No deaths reported during active treatment phase of study or major findings from laboratory, hematology, or histologic evaluations
One incidence of death occurring during screening period due to bleeding ulcer
Jeppesen PB et al. Gut. 2011;60:

33. Trials 020 i 021 P<0,005 ≥ 20% PN vol reduction after 20 (24) weeks
Jeppesen PB i wsp. Gastroenterology, 2012; 143: 1473 – 81,
Schwartz LK et al. Clin. Transl. Gastroenterology 2016; 7, e142; doi: /ctg

34. Trials 020 & 021 PN volume reduction
24 weeks treatment
N=43 (PBO)
135 weeks tratment
N = 65
PN volume reduction
(baseline = 12,9 L/7d)
4,4 L/7d
(2,3 L/7d) p < 0,001
- 7,6 L/7d
PN frequency reduction (≥ 1 inf/7d)
54% patients
(23%) p < 0,005
70% patients
Weaning off PN
10 patients
Jeppesen PB i wsp. Gastroenterology, 2012; 143: 1473 – 81,
Schwartz LK et al. Clin. Transl. Gastroenterology 2016; 7, e142; doi: /ctg

35. Trials 020 & 021
Schwartz LK et al. Clin Transl Gastroenterol. 2016;7:1-9

36. STEPS Safety Results (1/3)
Safety analysis population included 85 subjects who received at least one dose of study drug
The rate of AEs, SAEs, TEAEs, or study discontinuations were comparable between groups
Teduglutide-treated
n=42
Placebo
n=43
Total
N=85
Treatment-related serious AEs
15 (36%)**
12 (28%) 27
≥1 TEAEs during study
35 (83%)
34 (79%) 69
TEAEs leading to study discontinuation*
2 (5%)**
3 (7%) 5
Deaths
The number of AE leading to study discontinuation was low.
*None considered serious
**Deemed related to study drug (acute cholecystitis and small intestinal stenosis) and both resolved
Jeppesen PB, Pertkiewicz M, Messing, B, et al..Gastroenterology. 2012;143:

37. STEPS Safety Results (2/3)
The most frequently reported (TEAE) in the teduglutide-treated groups were gastrointestinal (GI) in nature
*Complications defined as reports of swelling, growth, hypertropy, enlargement, or increased size of stoma or stoma nipple
Stoma change (stoma nipple enlargement, hypertophy) seems to be a visible sing of bowel response to GLP-2 treatment.
**Includes catheter-related infection, central line infection, catheter sepsis, infective thrombosis, and bacteremia
Jeppesen PB, Pertkiewicz M, Messing, B, et al.. Gastroenterology. 2012;143:

38. STEPS Safety Results (3/3)
Laboratory/Chemistry/Hematology
No major findings in teduglutide or placebo groups
Development of anti-teduglutide antibodies
Six subjects from teduglutide group and none in placebo group developed teduglutide antibodies
Antibodies were non-neutralizing and without evidence of decreased effect on PS volume reduction or evidence of systemic hypersensitivity or other clinically significant sequelae
Body weight changes
Increase in body weight in the teduglutide group (1.0 ± 3.7 kg)
Decrease in body weight in placebo group (-0.6 ± 2.8 kg)
Jeppesen PB, Pertkiewicz M, Messing, B, et al. Teduglutide Reduces Need for Parenteral Support Among Patients With Short Bowel Syndrome With Intestinal Failure. Gastroenterology. 2012;143:

39. Long-Term, STEPS-2 Safety Results
Colonoscopies
50 subjects underwent 51 colonscopies during or as follow-up for STEPS-2.
Gastrointestinal polyps reported in 9 subjects (n=3 TED/TED; n=6 PBO-TED) within or at the end of 24- month treatment with teduglutide.
2/9 had polyps at baseline
Histopathology: adenoma (n=5), hyperplastic polyp (n=1), rectal inflammatory polyp (n=1), and unclassified (n=2; colonscopies done outside study procedures)
No cases of intestinal dysplasia or malignancy
Schwartz LK, O’Keefe S, Fujioka K, et al. Long-term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Shore Bowel Syndrome. Clin Transl Gastroenterol. 2016;7:1-9

40. Long-Term, STEPS-2 Safety Results
Antibodies:
Ted-specific antibodies detected in 37/87 subjects (n=18/37 (49%) TED/TED and n=19/50 (38%) combined NT/TED and PBO/TED) during STEPS-2
No neutralized antibodies were detected
Schwartz LK, O’Keefe S, Fujioka K, et al. Long-term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Shore Bowel Syndrome. Clin Transl Gastroenterol. 2016;7:1-9

41. Long-Term, STEPS-2 Safety Results
Vital signs:
Mean body weight and body mass index remained constant (mean ±SD: -0.4 ±5.0 kg and -0.2 ±1.7 kg/m2, respectively)
Plasma calcium, magnesium, or phosphate: no substantial shifts
Mean albumin levels remained stable; mean liver enzymes either numerically decreased or remained near baseline
Kidney function tests, including plasma creatinine levels: no changes from baseline
Schwartz LK, O’Keefe S, Fujioka K, et al. Long-term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Shore Bowel Syndrome. Clin Transl Gastroenterol. 2016;7:1-9

42. Long-Term, STEPS-2 Safety Results
Treatment-emergent adverse events(TEAEs) occurred in 84/88* (95%) patients enrolled in STEPS-2
Most commonly reported TEAEs were abdominal pain (34%), catheter sepsis (28%), episodes of decreased weight (25%), asthenic conditions (23%), and febrile disorders (20%)
56/88 (64%) of subjects experienced treatment-emergent serious adverse events (TESAEs)
16 subjects discontinued treatment due to TEAEs
4/37 (11%) in TED/TED group; 12/51 (24%) in PBO/TED+NT/TED group
PBO/TED+NT/TED, patients randomized to placebo (PBO) or not treated (NT) in placebo-controlled STEPS study; TEAE=treatment emergent adverse event; TED/TED, patients randomized to teduglutide (TED) in placebo-controlled STEPS study
*N=88 Intent-to-treat population
Schwartz LK, O’Keefe S, Fujioka K, et al. Long-term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Shore Bowel Syndrome. Clin Transl Gastroenterol. 2016;7:1-9

43. Long-Term, STEPS-2 Safety Results
Three deaths occurred in the STEPS-2 study:
A 48-year-old-man from metastatic adenocarcinoma to the liver (considered treatment-related by investigator) in NT/TED group
History of Hodgkin’s disease, treated with chemotherapy and radiotherapy two decades earlier, died 10 days after metastatic adenocarcinoma diagnosis with primary tumor likely to be gastrointestinal. The malignancy diagnosis occurred 11 months after TED treatment initiation. Teduglutide was discontinued.
A 64-year-old-man from non-small cell lung cancer (not considered treatment- related) in PBO/TED group
History of smoking and asbestos exposure; died 5 months after non-small cell lung cancer diagnosis. The malignancy diagnosis occurred 3 months after TED treatment initiation. Teduglutide was discontinued.
A 70-year-old man from sepsis (not considered treatment-related) in TED/TED group
Died from sepsis 15 days after hospitalization for a catheter and urinary tract infection; hospitalization occurred 28 months after TED treatment initiation. Teduglutide was not discontinued.
Schwartz LK, O’Keefe S, Fujioka K, et al. Long-term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Shore Bowel Syndrome. Clin Transl Gastroenterol. 2016;7:1-9

44. Cummulative results of phase III trials.
169 patients completed phase III clinical trials.
teduglutide 0,05 mg/kg/d were given 134 patients (up to 3,5 years)
Out of this group in 16 patients (12%) alimentary autonomy* had been achieved after 12 – 130 weeks of teduglutide treatment
* independency of parenteral support achieved during teduglutide administration in patients with stable SBS with optimalized baseline parenteral support requirements .
Jappesen et al. ESPEN 2014, poster PP131-SUN; Schwartz LK et al. Clin Transl Gastroenterol. 2016;7:1-9

45. Contraindications to teduglutide
Active cancer
Pregnancy and lactation
Hypersensitivity to teduglutide
Bowel obstruction (clinically important)
Active Crohn disease
Summary of Product Characteristic: Revestive at

46. Clinical problems associated with teduglutide therapy
Possible acceleration of GI neoplasm – obligatory colonoscopy before starting & endoscopic monitoring in the course of treatment
Possible exacerbation of pancreatic and biliary disorders
Summary of Product Characteristic: Revestive at

47. Clinical problems associated with teduglutide therapy
Possible exacerbation of bowel stenosis (adhesions, anastomotic stenosis),
Risk of fluid overload – congesive heart failure patients, kidney failure patients
Possible increase of the absorption of drugs
Summary of Product Characteristic: Revestive at

48. Interpretation of the results of clinical trials
Proven effectivness and safety of teduglutide treatment
Unresolved issues:
Significant differences in individual response to the treatment
Compliance with the complex of recomendations (diet, fluid intake etc)?
Autonomy absolute or conditional?
Durability of effects of the treatment.
Minimal lenght of remnant bowel fit for teduglutide therapy

49. Who may benefit with teduglutide therapy?
All SBS patients?
Patients with reasonable chance for regaining of PS independence?
Patients not tolerating standard treatment
Catheter complications
Lost of venous access
Difficulties with maintaining of metabolic stability
Patients with severe IF and PS dependency
ultra SBS, terminal jejunostomy
COSTS (?)
Improvement of standard treatment!!!
Presented data - property dr M Kunecki

50. Restoring of alimentary autonomy*
SBS type I i II
Low baseline PN volume requirements (< 12 L/week, < 4 infusions/week)
Previous attempts to weaning off PS failed!!!
No contraindications to teduglutide
Revestive therapy – up to 24 months (?)
Assessment of the effectivness of the therapy
*recomendation of experts panel of Polish Network of IF Treatment Centers
Kunecki M et al. Adv in Clin Nutrition, 2016, 12, 2 (39), 2-7

51. PN independence after teduglutide treatment anatomy & lenght of remnant bowel (N=16)
No data

52. PN independence baseline PN volume.
Baseline PN volume L/7d

53. PN independence Duration of PS at time of indepenence
Duration of PS [years]

54. PN dependency 12 after teduglutide discontinuation (N = 37)
Patients with PN volume reduction after 24 weeks of teduglutide
Further reduction PN volume
PN volume reduction maintained
PN volume increased
Compher Ch. i wsp, JPEN, 2011, 35,

55. Improvement of bowel absorption in severe IF patients – patients characteristic*
SBS of all types, severe IF,
(?) cm < bowel lenght < 50 cm
Terminal jejunostomy, no possibilities of surgery .
Unstable IF
Incidences of dehydration/dyselectrolytemia
Kidney failure
Metabolic acidosis
High risk of organ failure
PNALD/IFALD (other causes of liver abnormalities excluded!!!)
Criteria not clear
*recomendation of experts panel of Polish Network of IF Treatment Centers
Kunecki M. et al. Adv in Clin Nutrition, 2016, 12, 2 (39), 2-7

56. Frequency of liver disorders in long term PN patients
Treatment rationele:
Optymalization of energy administration
Improvement of quality of care (catheter complications reduction)
Reduction of LE
LE change
Improvement of intestinal absorption
Percentage of IFALD/PNALD
Cavicchi M, et al. Ann Intern Med 2000;132(7):

57. Mean bilirubin levels observed on teduglutide treatment (020 & 021)
GATTEX® (teduglutide [rDNA origin]) Briefing Document, Advisory Committee Meeting 16 October 2012