Teduglutide significantly reduced the need for parenteral support in patients with short bowel syndrome and intestinal failure, based on data from 85 adults in a randomized, controlled multicenter trial. The findings were published in the December issue of Gastroenterology.
Patients with short bowel syndrome and intestinal failure (SBS-IF) have inadequate intestinal absorption and require parenteral support (PS) to maintain fluids, electrolytes, trace elements, vitamins, and nutrient balances, said Dr. Palle Bekker Jeppesen of Rigshospitalet in Copenhagen and colleagues.
Source: American Gastroenterological Association
Data from previous open-label studies suggest an association between teduglutide and clinically meaningful reductions in wet weight and energy, which may reduce the need for PS in these patients, the investigators noted.
The researchers randomized 86 adults with SBS-IF to either 0.05 mg/kg per day of teduglutide or a placebo. One patient was randomized in error; complete data were available for 42 teduglutide patients and 43 placebo patients.
Significantly more patients in the teduglutide group responded to treatment, compared with the placebo group (63% vs. 30%). This response was defined as sustaining a 20%-100% reduction from baseline in weekly PS volume during weeks 20-24. "Small bowel length did not appear to be a predictor of response," the researchers noted.
The high placebo response may be explained by examining the fluid composite effect, a measure of the combined effects of teduglutide on PS volume reduction as well as the ability to reduce oral fluid intake and increase urine output volume, the researchers noted.
"In the current study, where protocol modifications encouraged earlier and more aggressive PS reductions, significantly larger PS reductions were also achieved in patients receiving placebo, but subsequently these patients had to increase their oral fluid intake significantly to maintain urine production and hydration constant," they said.
After 24 weeks, overall PS volume was reduced by 32% from baseline in teduglutide patients, compared with 21% in placebo patients. Although no patients in either group were completely weaned from parenteral support at 24 weeks, the difference in PS volume reduction was significantly greater in the teduglutide group.
The average weekly PS volume in teduglutide patients decreased significantly from 12.5 L/wk at baseline to 8.1 L/wk at week 24. The placebo patients also had a significant decrease in average weekly PS volume, from 13.4 L/wk at baseline to 11.1 L/wk at week 24.
Treatment-ending adverse events were similar between the two groups; 5% of teduglutide patients and 7% of placebo patients discontinued treatment because of such events during the study period. The most frequently reported treatment-emergent adverse events included abdominal pain, abdominal distension, nausea, and gastrointestinal stoma complications.
Although the study did not specifically assess quality of life measures, significantly more teduglutide patients had at least 1 day off PS, compared with placebo patients, which could help to "liberate considerable time for unhindered daytime activities or undisturbed sleep," the researchers said.
The study did not address the possible benefit of teduglutide therapy earlier in the course of SBS, or the duration of effect after patients discontinued teduglutide, the researchers added.
However, the findings indicate that teduglutide was safe and well tolerated, and "could positively add to the limited treatment armamentarium" for patients with SBS-IF.
Dr. Jeppesen and several coauthors have served on the advisory board of and as consultants to NPS Pharmaceuticals, the company that funded the study. One author is an employee of NPS Pharmaceuticals.