See “Experience With Teduglutide in Pediatric Short Bowel Syndrome: First Real-life Data” by Ramos Boluda et al on page 734.
The use of a synthetic GLP-2 (glucagon like peptide-2) analogue, teduglutide has opened the door to a new dimension of treatment for children with intestinal failure (IF)-related short bowel syndrome (SBS) (1,2). In the first published cases outside clinical trials, Ramos Boluda et al (3) (in this issue) describe a substantial improvement in the outcome for SBS-related chronic IF children. The majority of their reported cases, 12 of 17 (70%) gained enteral autonomy by 12 months of treatment. Three patients weaned off PN within 3 months of starting teduglutide, a further 4 by 6 months and 6 others by 12 months having previously failed to respond to all attempts to reduce PN (3). Ramos Boluda et al considered their outcome was even better than that reported in the paediatric clinical studies (1,2). The most recently published study data reports on outcome after just 24 weeks treatment (2). At 24 weeks, 18/26, (69%) patients had weaned PN by at least 20% whereas Ramos Boluda et al (3) reported that 13/17 (76%) of cases had done so. Alongside the good response to treatment, their studies and the Ramos Boluda et al article were reassuring with regard to adverse events. Children on teduglutide treatment had a similar incidence of adverse events, such as IF-related problems and intercurrent childhood infections to those given standard care (1,2).
It is important to stress that the majority of infants and children with IF-related SBS wean off PN within a few weeks or months of acquiring the condition. The children treated with teduglutide by Ramos Boluda et al and in the studies were a small sub-group of cases that have failed to progress to develop enteral autonomy and remain dependent on PN for months and years, plateauing in their need for PN. Many of these patients have “ultra” short bowel (4) that would previously have been considered incompatible with survival and still is in some medical settings, even when “hi-tech” treatment is available.
The advent of synthetic GLP-2 is at an opportune moment for 2 reasons. Firstly, there have been major advances in the outcome of IF (4) and secondly there is an increasing incidence of long-term IF in children (5). Over the last 25 years, despite the lack of major new treatments, the outcome of chronic irreversible intestinal failure (IF) has transformed from almost certain death in childhood to a high chance of survival into adult life—even when still PN-dependent. The best outcome has been achieved when care is led by an experienced multidisciplinary IF rehabilitation service that supports parents in managing the invasive “hi-tech” treatment at home (4). Families have the best chance of a good quality of life when the affected child is discharged home with parents formally trained (6) in how to connect and disconnect the central venous catheter (CVC) in an aseptic manner and troubleshoot any complications that may arise. The PN is usually infused overnight with the CVC clamped off during the day to enable school attendance with participation in sport, swimming, and other daytime childhood activities (6). The most frequent serious complications of long-term PN have been minimized by improvements in all aspects of care including: nursing practices when connecting/disconnecting the CVC; use of antibacterial line locks to limit the chance of catheter-related bloodstream infection (CRBSI); urgent medical care with immediate antibiotic treatment for suspected CRBSI; using radiological control when replacing the CVC in order to minimize vascular damage; pharmacological advances in PN composition and components, such as new mixed lipid emulsions; introduction of oral/enteral nutrition at the earliest postoperative opportunity; and national and international guidelines on all aspects of the use of PN (6). In addition, surgical management of strictures, adhesions, and use of lengthening techniques for dilated intestine may improve enteral nutrient absorption (4).
Despite the best possible care, chronic IF can adversely affect quality of life (4,6). Affected children are frequently connected to PN infusion for 12 hours 7 nights a week. Sleep can be disturbed with the need to pass urine and/or defaecate and the PN infusion pump alarming. There is the constant need for vigilance with the risk of acute potentially life-threatening CRBSI. If the child develops a significant fever she or he needs to immediately go to the nearest paediatric in-patient service to have urgent blood cultures and to start in-patient treatment with intravenous antibiotics whilst the result is awaited.
One of the difficulties of teduglutide use is deciding, which patients should be prioritized for treatment. GLP2 treatment is costly, particularly as in the more severe cases, it might need to be continued for many years or life. Treatment appears to be effective in children with SBS whatever the aetiology (2) as long as clinical care has been optimized. There has been much debate as to which intestinal remnant might respond best and whether to prioritize patients near to weaning off PN or those most heavily dependent on treatment. For example, is the benefit of reducing PN infusions from every night, that is, 7 nights a week to 5 nights greater than weaning from 2 nights to entirely stopping PN? And in the second situation, GLP-2 treatment might only be needed for a few months.
Intestinal GLP-2 secretion is mainly concentrated in the ileal “L” cells (3). Virtually all children with SBS have loss of ileum and would be expected to have low innate GLP-2, hence they should benefit from teduglutide supplementation on theoretical grounds.
If more widespread use of teduglutide is as successful as that reported by Ramos Boluda et al, use of a GLP-2 analogue should be a routine treatment strategy for SBS. Surveillance endoscopy is recommended in patients on longer term treatment in view of the hypothetical risk of neoplasia (7). Other GLP-2 analogues are currently under development and there is a growing interest in the use of other intestinal hormones, such as GLP-1 (8,9).
In conclusion, use of teduglutide in children with SBS who are lingering on PN treatment, despite the best IF rehabilitation management by an experienced multidisciplinary team, gives new hope for earlier recovery from IF.
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