The role of somatropin in short bowel syndrome

Posted by Doctor Mai Vien Phuong - Department of Medical Examination & Internal Medicine - Vinmec Central Park International General Hospital.

An important goal when treating patients with short bowel syndrome (short bowel syndrome) requiring parenteral nutrition or fluid support is to reduce dependence on this support and completely eliminate the use of medications. this whenever possible.

Use of parenteral nutrition in short bowel syndrome is associated with reduced quality of life and a number of complications arising from not only parenteral nutrition, but also the catheters used to infuse nutrition outside the intestine. These complications can include catheter-associated blood infections and venous thrombosis, metabolic bone disease, liver disease, and kidney failure.
An important goal when treating patients with short bowel syndrome requiring intravenous support (i.e. parenteral nutrition or IV fluids) is to reduce reliance on this support, and whenever possible , completely eliminating its use. The need for parenteral nutrition decreases as the intestine adapts after resection, allowing greater absorption of nutrients and fluids. More than 50% of adults with short bowel syndrome are able to completely discontinue parenteral nutrition within 5 years of diagnosis. In contrast, the probability of eliminating the use of parenteral nutrition is <6% if not performed successfully during the first 2 years after the individual's last bowel resection. Several clinical factors may serve as useful predictors of the success of eliminating the use of parenteral nutrition in short bowel syndrome. The presence of colon and the remaining length of small intestine function are the most important factors. The permanent need for parenteral nutrition usually occurs when there is <50-70 cm of small bowel with continuous colon or <100-150 cm of small intestine without colon.

Following the 2 - 3 year period of intestinal best adaptation after bowel resection, the homeostasis/maintenance phase begins where no spontaneous intestinal adaptation is thought to occur. Intestinal failure is usually considered permanent when parenteral nutrition is required after this period. There is great interest in the use of growth factors in patients with short bowel syndrome who cannot achieve intestinal independence during the acclimatization phase despite optimized diet and management. medical management. The current understanding of the adaptive process has led to the study of hormones, nutrients and growth factors in experimental models and in humans with short bowel syndrome. Several pharmacological agents have been shown to induce nutritional properties on the intestinal epithelium in animal models of short bowel syndrome.

An important goal when treating patients with short bowel syndrome requiring parenteral nutrition or fluid support is to reduce dependence on this support and completely eliminate the use of these agents whenever possible. body. There is great interest in the use of growth factors in patients with short bowel syndrome who cannot achieve intestinal independence during the acclimatization phase despite optimized diet and management. medical management. Several pharmacological agents have been shown to induce nutritional properties on the intestinal epithelium. In this section we will focus on somatropin, a recombinant human growth hormone, and teduglutide, a recombinant human peptide-2 glucagon analog, currently approved nutritional factors available. for use as enteral nutritional support in short bowel syndrome.

In a recent prospective, uncontrolled case series, Zhu and colleagues used a similar treatment program and produced very similar, long-lasting results. A prospective, randomized, placebo-controlled phase III trial performed at 2 subsequent centers was then performed. Forty-one patients with short bowel syndrome dependent on parenteral nutrition (most with a continuous internal colon) were enrolled and studied in a 6-week inpatient-like setting; 2 weeks of diet and medication (i.e. antidiarrheals and proton pump inhibitors) and parenteral stabilization followed by a 4-week treatment period.
Patients were randomly divided into 3 groups: somatropin (0.10 mg/kg subcutaneously once daily) with glutamine, somatropin without glutamine, and placebo with glutamine. Significant reduction in both growth hormone-treated groups according to parenteral nutrition requirements (primary end point), including parenteral nutrient volume, parenteral nutrition energy, and parenteral nutrition infusion frequency at the end of the 4-week treatment period.
However, the extent of the reduction in parenteral nutrition remained significantly decreased during the 12-week observation period in the glutamine-only somatropin group; Importantly, this group also lost about 5 kg. Although tolerable, peripheral edema and musculoskeletal complaints were common in the somatropin-treated group. On the basis of this evidence, and the safety of the treatment program, the FDA approved the use of somatropin in December 2003 as a short-term (4-week) adjunct to the cessation of parenteral nutrition. in patients with short bowel syndrome. To date, somatropin has not been approved by the European Medicines Agency for this indication.

Despite reports of success with growth hormone, randomized, controlled nutritional balance studies have found conflicting evidence about nutrient absorption and wet weight when using a combination of somatropin and this glutamine (but no conventional diet or drug optimization). This has led to much skepticism surrounding the long-term benefits of this approach, and its clinical use remains controversial.
In addition, the side effects of somatropin including peripheral edema, arthralgia, and carpal tunnel syndrome are significant, further limiting its application to clinical practice. Concern exists about the possibility of an increased risk of colorectal cancer in patients receiving somatropin if used for a longer period of time. Finally, there is concern about the feasibility of replicating the results of a pivotal trial in an ambulatory setting without the same daily monitoring and counseling. Clearly, admitting a patient for 4 weeks to optimize diet, hydration and medical therapy and somatropin administration will be quite a challenge in today's healthcare environment.

Somatropin is contraindicated in patients with active cancer and those with severe disease. It is associated with acute pancreatitis, impaired glucose tolerance, type 2 diabetes, carpal tunnel syndrome, and arthritis. In the US, the cost for a 4-week course of somatropin is about $20,000. An economic analysis of health care costs associated with growth hormone use estimated a 2-year savings of $85,474 assuming that 34% of growth hormone-treated patients eliminated employment. using parenteral nutrition within 6 weeks of treatment and 31% still not using parenteral nutrition after 2 years. However, keep in mind that patients in clinical trials are studied in inpatient (though not hospital) conditions, and receive daily visits and education/counseling; expenses are not included in the above amount. It has not been widely adopted into clinical practice more than a decade after its approval. Furthermore, the role of repeated course(s) or prolonged treatment with somatropin needs further investigation.

References
Messing B, Crenn P, Beau P, et al. Long-term survival and parenteral nutrition dependence in adult patients with the short bowel syndrome. Gastroenterology 1999;117:1043-1050. Amiot A, Messing B, Corcos O, et al. Determinants of home parenteral nutrition dependency and survival of 268 patients with non-malignant short bowel syndrome. Clin Nutr 2013;32:368-74. Byrne TA, Persinger RL, Young LS, et al. A new treatment for patients with short-bowel syndrome: growth hormone, glutamine, and a modified diet. Ann Surg 1995;222:243-254. Byrne TA, Cox S, Karimbakas M, et al. Bowel rehabilitation: an alternative to long-term parenteral nutrition and intestinal transplantation for some patients with short bowel syndrome. Transplant Proc 2002;34:887-890.