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P428. New opportunities overcoming of the secondary inefficiencies of the anticytokine therapy in patients with inflammatory bowel disease

O. Knyazev1, V. Sagynbaeva1, I. Ruchkina1, A. Parfenov1, P. Shcherbakov1, A. Konoplyannikov2, L. Lazebnik3, 1Central Research Institute of Gastroenterology, Moscow, Russian Federation, 2Medical Radiological Research Center, Obninsk, Russian Federation, 3Clinical Hospital 33 of Moscow City, Moscow, Russian Federation

Background

Episodic infusions of infliximab (IFX) in some cases up to 35%, lead to the formation of antibodies to infliximab (ATI). In some patients treatment of IFX can lead to infusion reactions, reducing the effectiveness and duration of response to this therapy.

Objectives: To study the effect of transplanted allogenic mesenchymal stromal cells (MSCs) of bone marrow levels of ATI, and the clinical course of patients with inflammatory bowel disease (IBD) with the secondary inefficiencies of the anticytokine therapy.

Methods

A total of 39 patients with IBD treated with infliximab, 21 of them – ulcerative colitis (UC) (12 males, 9 females) and 18 – Crohn's disease (CD) (7 males, 11 females). The patients' age 16–70 years, mean age was 37.8±2.5. Induction was carried out under the scheme 0–2-6, maintenance therapy after 8 weeks of the year. The total number of infusions in patients ranged from 8 to 19. After a year of therapy were assessed for CDAI and UC Rahmilevitz index, measured levels of ATI. The level of ATI in the serum of patients was determined by ELISA using the test kits “Bender Med systems” (Austria).

Results

12 (30.7%) patients with IBD had with ATI (5 CD, 7 UC), revealed a high titer of antibodies to the drug – from 69 to 314 ng / ml (n<5 ng/ml), and the mean value – 177.8±30.6 ng/ml. In these patients improve ATI accompanied by clinical deterioration: the emergence of pain, increased stool frequency with blood and mucus, decrease in hemoglobin levels, as well as the appearance of allergic reactions. CDAI rose an average of 103.9±13.2 to 135.2±15.0 points (p > 0.05), the index Rahmilevitz 1.3±0.2 to 2.9±0.4 points (p > 0.001). Patients performed a one-time system transplantation of allogeneic bone marrow MSCs to enhance the effectiveness of ongoing anti-inflammatory therapy. After 4 weeks the level of ATI in all patients decreased from 285 to 0–0.8 ng/ml to 7–15 ng/ml, an average of 8.5±2.2 ng/ml (p < 0.001). This decrease was accompanied by a decrease in the activity of CD (CDAI decreased to 68.5±4.6) and UC (lower index Rahmilevitz to 1.3±0.2).

Conclusion

Transplantation of allogeneic mesenchymal stromal cells of bone marrow promotes overcoming of the secondary inefficiencies of the anticytokine therapy in patients with IBD and reduces the level of ATI to patients with CD and UC.