Monthly Key Publication Reviews

Publication: Harpain, F, Schlager, L, Hütterer, E, et al. Teduglutide in short bowel syndrome patients – A way back to normal life? JPEN J Parenter Enteral Nutr. 2021; 00 1– 10. https://doi.org/10.1002/jpen.2272

Reviewer: Sneha G. Bhat, MD, FACS, CNSC. Assistant Professor of Surgery, UT Southwestern Medical Center, Dallas, Texas.

Why is this paper important? Short bowel syndrome (SBS) is an intestinal failure that occurs due to inadequate absorption and/or digestion of nutrients, often after extensive or multiple intestinal resections. Manifestations of SBS can occur due to loss of intestinal absorptive surface area, removal of the ileocecal valve, or through loss of site-specific endocrine cells, transport processes, or GI hormones.   The subsequent malabsorption of micro or macronutrients, water, and/or electrolytes leads to malnutrition and requires tailored nutrition support for optimization.  The prevalence of SBS is about 3-4 million patients and can occur in approximately 15% of adult patients undergoing intestinal resection.  Given the vast complications associated with SBS, improved understanding of any adjuncts for medical optimization of these patients is crucial. Teduglutide is a dipeptidyl-peptidase, degradation-resistant GLP-2 analogue, which recent literature has shown to improve functional and structural capacity of the intestines with repeated administration . This observational, retrospective study includes 13 patients in their final analysis and looks at various functional and symptomatic responses, nutrition status, as well as adverse events and SBS treatment-related complications. One of the main outcomes was enteral autonomy, or complete independence of parenteral support, whether PN or IVFs. Prior to this study, success rates of enteral autonomy with teduglutide use have ranged from anywhere between 12 -29%.  When these thirteen patients were treated by a multidisciplinary team and teduglutide therapy was utilized, decreased dependence of parenteral support was documented, as well as enteral autonomy in >90% of the cohort. Although a small study, this paper shows that teduglutide may be an effective adjunct in the treatment of SBS with intestinal failure and highlights the need for further larger-scale clinical trials utilizing this medication in an unrestricted clinical setting.

Summary: Glucagon-like peptide 2 (GLP-2) is known to stimulate the growth of intestinal mucosa via stimulation of crypt cell growth, inhibition of enterocyte apoptosis and impedes gastric emptying, stimulates intestinal blood flow, and increases intestinal barrier function . Thus, GLP-2 analogues, such as teduglutide, could potentially aid in intestinal rehabilitation and achieving enteral autonomy. In this retrospective observational study performed at a single tertiary care institution, at the Medical University of Vienna, analysis was performed of all patients with non-malignant SBS with intestinal failure between June 2016 to June 2020, with 13 patients included in the final analysis. These patients underwent a patient-tailored plan developed by a multidisciplinary team consisting of GI surgeons, gastroenterologists and dieticians, and received the approved standard dose of daily treatment with teduglutide (0.05 mg/kg/BW) as part of their therapy. Patient demographics were documented, and outcomes were measured as functional response (parenteral requirements, oral intake, and urinary output), symptomatic response (stool characteristics, dietary habits and sleep disruption), nutrition status response, and adverse events (AEs) or complications. Enteral autonomy, defined as complete independence of even periodic parenteral support, was a main outcome measured, and twenty-four weeks after teduglutide therapy initiation 9 of 13 patients, (69%) reached enteral autonomy with complete discontinuation of PS. Over the total length of follow-up, the rate of patients who reached enteral autonomy increased to 12 of 13 patients (92%). At least one AE occurred in nine of 13 of patients (69%), with the most common complaints being GI related, but no AE led to permanent discontinuation of teduglutide treatment. Temporary dose adjustments or injection interval lengthening were enacted in five patients (38%). One death occurred during the study period (respiratory failure because of systemic scleroderma). Additionally, despite concerns regarding the potential of teduglutide to stimulate tumorigenesis due to its role as an intestinotrophic growth factor, all patients received pre-intervention screening colonoscopies and periodic follow-up colonoscopies, but no polyps or signs of colorectal tumorigenesis was noted.

Commentary: Teduglutide is emerging as a potentially highly effective medication that could aid in reducing parenteral support in SBS patients. Treatment of these patients with intestinal failure by a multidisciplinary team using a patient-tailored unique approach increases the rate of enteral autonomy and decreases overall morbidity in this population. Despite multiple clinical trials showing teduglutide treatment to decrease total burden of parenteral support, the rates of reported enteral autonomy remain <30%, until this paper was able to show a 92% rate of enteral autonomy. It is important to note that this is a retrospective, single-institution study with a small total patient size of only13 individuals. Although this is often the nature when examining rare disease entities, it is difficult to generalize this observational data, especially when further dissecting the study population demographics. Of the 13 patients, an overwhelming majority (8 of 13 patients) are non-geriatric patients with inflammatory bowel disease. In addition, over 75% (10 of 13 patients) have some level of continuity with their colon, rather than an ileostomy or jejunostomy. Additionally, the high rate of inter-individual heterogeneity in the patient population, as well as the small sample size, make this data hard to extrapolate to the general SBS population. Additional clinical studies are required in order to characterize the benefit of teduglutide use in SBS intestinal failure and to verify the findings of this paper. 

References:

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