Клиническая и морфологическая оценка эффективности применении тедуглутида у детей с синдромом короткой кишки: пилотное исследование в России

Abstract

The main aim of rehabilitation in patients with short bowel syndrome (SBS) is the reduction of parenteral nutrition (PN) dependency. Glucagonlike peptide 2 analog teduglutide is a trophic factor with a potential ability to reduce intestinal insufficiency. Objective. To evaluate the clinical efficacy of teduglutide and morphological markers of intestinal adaptation in children with SBS. Patients and methods. The study included 26 patients with aged 2.5 to 14 years (5 ± 2.5 years), dependent from PN during 52 ± 20 months (min 29, max 116 months) before study and receiving teduglutide at a dose of 0.05 mg/kg/day. In 11 patients SBS occurred because of volvulus or thrombosis, in 7 – Hirschsprung disease and in 9 – intestinal atresia; the residual intestinal length was 30 ± 28 cm. The study design included three control points: initiation of therapy with teduglutide, 6 months and 1 year after therapy. Physical development, need for parenteral nutrition, and intestinal mucosa morphometry (n = 18) were assessed. The efficacy of treatment was stated if 1 of 3 following criterion was seen: the reduction of PN ≥20%, more days without PN or PN withdrawal. An increase in villus length by ≥100 μm was considered as a morphological criterion of adaptation. Results. Reduction in PN dependence was noted in 69% of children. Morphological adaptation of the small intestinal was noted in 66% of children, positive correlation was found between villous height and the duration of therapy (r = 0.39, p < 0.05). The length of the preserved ileum was positively correlated with the possibility of morphological adaptation (r = 0.58, p < 0.05). Better morphological adaptation was demonstrated by patients with acute intestinal blood flow disorders. The use of teduglutide allowed to maintain normal Z-score values during a significant reduction in the proportion of PN. Conclusion. Teduglutide demonstrated its safety and efficacy in children with SBS in the terms of PN dependency reduction and morphological adaptation. However, these results require further investigation in larger cohorts in multicenter trials. Key words: children, short bowel syndrome, teduglutide, parenteral nutrition, intestinal adaptation