Teduglutide in Patients With Active Crohn’s Disease and Short Bowel Syndrome
Bibliographic record
Abstract
To the Editors: Short bowel syndrome (SBS) is a malabsorptive disorder often necessitating parenteral nutrition (PN) support to maintain electrolyte, fluid, and nutritional homeostasis.1,2 Patients with refractory Crohn’s disease (CD) are at high risk for SBS as a result of repeated surgical resections or extensive luminal inflammation that reduces absorptive capacity.3 The risk of chronic intestinal failure requiring PN in patients with CD has remained stable despite the introduction of biologic therapies, highlighting a need for improved therapeutic options.4 Teduglutide is a glucagon-like peptide (GLP)-2 analogue that is approved for the treatment of patients with PN-dependent SBS.5 However, there may be hesitancy to use teduglutide in patients with active CD because of theoretical concerns that its intestinotrophic actions may exacerbate inflammation. Here, we present 2 cases of patients with active CD and SBS treated with combination teduglutide and biologic therapy with no disease flare. The first case is a 38-year-old male with ileocolic, stricturing CD, previously failing immunosuppressants, infliximab, and adalimumab. He underwent multiple surgeries resulting in SBS and daily PN in 2011. Teduglutide was commenced in 2017, and he completely weaned off PN within 7 months. Recurrence of CD at the ileocolic anastomosis was treated with ustekinumab, and both treatments have since been maintained for 15 months without any adverse events. The second case is a 39-year-old male with steroid-dependent stricturing small bowel CD, previously failing immunosuppressants, infliximab, and adalimumab. After multiple resections, he was left with a jejunocolic anastomosis and 60 cm of residual small bowel length. Daily PN was initiated in 2003. He was initiated on vedolizumab and 6-mercaptopurine in 2016, and teduglutide was added in 2017, with significant improvement in oral intake, reduced stool output, and weight gain. His PN requirements reduced to 1 night per week, and he has been maintained on combination therapy without any adverse events. Patients with CD were initially excluded from phase III randomized controlled trials evaluating teduglutide efficacy and safety6,7 because of a perceived risk of exacerbating mucosal inflammation. However, the management of patients with PN-dependent CD with SBS is especially challenging because most will continue to have active inflammation that compromises the functional absorptive capacity of residual small bowel. Treatment strategies that optimize both inflammatory control and nutritional status are required. Here, we present 2 patients with CD and SBS safely treated with combination biologic and teduglutide, allowing control of intestinal inflammation and substantial reductions in PN support. Patient consent: Informed consent has been obtained from all patients. Version: April 1, 2019.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.006 | 0.004 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".