New possibilities for overcoming the secondary inefficiency of anti-cytokine therapy in patients with inflammatory bowel diseases


Cite item

Full Text

Abstract

A search for ways to overcome the secondary inefficiency of anti-cytokine therapy (ACT) with infliximab (IFX) in patients with inflammatory bowel diseases (IBD) remains relevant and determines the need for new approaches to solving this problem. The secondary inefficiency of ACT has been found to depend on the level of antibodies to IFX (anti-IFX Ab). The Department of Intestinal Pathology, Central Research Institute of Gastroenterology, is investigating the mechanisms for the occurrence of primary and secondary inefficiency of ACT, as well as ways to overcome them by cultured allogenic bone marrow mesenchymal stromal cells (MSC). In the framework of the searching investigation evaluating the efficiency and safety of MSC in patients with IBD, the investigators revealed that was a phenomenon of a decrease in anti-IFX Ab and came to the conclusion that the secondary inefficiency of ACT should be overcome in a patient with ulcerative colitis (UC). The elevated anti-IFX Ab levels were directly associated with the worsening clinical and endoscopic picture of UC and with the enhanced activity of an inflammatory process. The administration of cultures MSC contributed to lower anti-IFX Ab levels, overcome secondary inefficiency (an escape phenomenon) during ACT, and enhanced IFX sensitivity. The clinical observation indicated that MSC administration reduced anti-IFX concentrations and promoted UC remission during IFX therapy. Thus, MSC transplantation can be considered as a promising method for overcoming the secondary inefficiency of ACT, which aids in increasing the previously lost response to anti-inflammatory therapy.

Full Text

Новые возможности преодоления вторичной неэффективности антицитокиновой терапии у больных воспалительными заболеваниями кишечника. - Аннотация. Поиск путей преодоления вторичной неэффективности антицитокиновой терапии (АЦТ) инфликсимабом (ИНФ) у больных с воспалительными заболеваниями кишечника (ВЗК) остается актуальным и обусловливает необходимость новых подходов к решению данной проблемы. Установлено, что вторичная неэффективность АЦТ зависит от уровня антител к инфликсимабу (АТИ). В отделе патологии кишечника ЦНИИГ проводится изучение механизмов возникновения первичной и вторичной неэффективности АЦТ, а также пути их преодоления с помощью культуры аллогенных мезенхимальных стромальных клеток (МСК) костного мозга. В рамках поисковой работы, оценивающей эффективность и безопасность МСК у больных с ВЗК, нами выявлен феномен снижения уровня АТИ и как следствие преодоление вторичной неэффективности АЦТ у больного язвенным колитом (ЯК). Повышение уровня АТИ напрямую связано с ухудшением клинической и эндоскопической картины ЯК, повышением активности воспалительного процесса. Введение культуры МСК способствовало снижению уровня АТИ, преодолению вторичной неэффективности (феномена "ускользания") при проведении АЦТ, и повышению чувствительности к ИНФ. Клиническое наблюдение показало, что введение МСК снижает уровень АТИ и способствует наступлению ремиссии ЯК на фоне терапии ИНФ. Поэтому введение культуры МСК можно рассматривать в качестве перспективного метода преодоления вторичной неэффективности АЦТ, способствующего повышению утраченной ранее чувствительности к противовоспалительной терапии.
×

References

  1. Ben-Horin S., Chowers Y. Review article: loss of response to anti-TNF treatments in Crohn's disease. Aliment Pharmacol Ther 2011; 33 (9): 987-995.
  2. Remicade (infliximab) Summary of Product characteristics (SmPC); dated June 17, 2011.
  3. Ducourau E., Mulleman D., Paintaud G. et al. Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases. Arthritis Res Ther 2011; 13: 105.
  4. Bartelds G.M., Krieckaert C.L., Nurmohamed M.T. et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA 2011; 305: 1460-1468.
  5. Plasencia C., Pascual-Salcedo D., Nuño L. et al. Influence of immunogenicity on the efficacy of long-term treatment of spondyloarthritis with infliximab. Ann Rheum Dis 2012; 71 (12): 1955-1960.
  6. Baert F., Noman M., Vermeire S. et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med 2003; 348: 601-608.
  7. Karmiris K., Paintaund G., Noman M. et al. Influence of trough serum levels and immumogenicity on long-term outcome of adalimumab therapy in Crohn's disease. Gastroenterology 2009; 137: 1628-1640.
  8. Pascual-Salcedo D., Plasencia C., Ramiro S. et al. Influence of immunogenicity on the efficacy of long-term treatment with infliximab in rheumatoid arthritis. Rheumatology (Oxford) 2011; 50: 1445-1452.
  9. Krieckaert C.L., Bartelds G.M., Lems W.F., Wolbink G.J. The effect of immunomodulators on the immunogenicity of TNF-blocking therapeutic monoclonal antibodies: a review. Arthritis Res Ther 2010; 12: 217.
  10. Ben-Horin S., Yavzori M., Katz L. et al. The immunogenic part of infliximab is the F(ab')2, but measuring antibodies to the intact infliximab molecule is more clinically useful. Gut 2011; 60 (1): 41-8.
  11. Steenholdt C., Bendtzen K., Brynskov J. et al. Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn's disease. Scand J Gastroenterol 2011; 46: 310-318.
  12. Meisel R., Zibert A., Laryea M. et al. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indolamine 2,3-dioxygenase-mediated tryptophan degredation. Blood 2004; 103: 4619 -4621.
  13. Kyriakou D.S., Alexandrakis M.G., Zachou K. et al. Hemopoietic progenitor cells and bone marrow stromal cells in patients with autoimmune hepatitis type 1 and primary biliary cirrhosis. J Hepatol 2003; 39; 5: 679-685.
  14. Corcione A., Benvenuto F., Ferretti E. et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006; 107: 367-372.
  15. Sotiropoulou P.A., Perez S.A., Gritzapis A.D. et al. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 2006; 24 (1): 74-85.
  16. Duijvestein M., Molendijk I., Roelofs H. et al. Mesenchymal stromal cell function is not affected by drugs used in the treatment of inflammatory bowel disease. Cytotherapy 2011; 13 (9): 1066-1073.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2013 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

 © 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies