THE EFFICIENCY OF POSTOPERATIVE PREVENTIVE TREATMENT BY ADALIMUMAB AND AZATHIOPRINE IN CROHN'S DISEASE

INTRODUCTION. About 75% of patients with Crohn's disease (CD) required surgery due to the complications of CD. Surgical treatment does not cure this disease. The question of appropriate therapy for the prevention of postoperative reccurence of CD remains open until now. The purpose of this study was to compare immunosuppressive and biological therapy as a postoperative preventive therapy. MATERIALS AND METHODS. 91 patients with CD who underwent surgery in the A.N. Ryzhykh State Scientific Center for Coloproctology of the Ministry of Health of Russian Federation from 2010 to 2017 were included in the study. Patients who had inflammation in the remaining areas of the intestine in the outcome of surgical treatment were excludedfrom the study. After surgery, patients were randomized into 3 groups. In the first group preventive therapy was carried out with azathioprine, in the second group with adalimumab, in the third group, patients received combination therapy with azathioprine and adalimumab. Clinical, endoscopical and laboratory assessment of disease activity was conducted at 3, 6 and 12 month after the surgery. RESULTS. During one year of preventive therapy with azathioprine, adalimumab, or a combination of this medications, relapse occurred in 17 patients (17/83, 20%). There were no statistically significant differences between the groups in any of the stages of evaluation. CONCLUSION: The data obtained in the study allow to conclude that the frequency of relapses of CD on postoperative preventive therapy does not depend on the specific drug, as well as on demographic and anamnestic parameters.

Crohn’s disease, relapse, treatment, adalimumab, azathioprine

1. Варданян, А.В. Илеостомия и ее эффективность при осложненных формах болезни Крона толстой кишки / А.В.Варданян, Ю.А.Шелыгин, В.Н.Кашников и соавт.// Вестник Северо-Западного гос.мед. университета им.И.И.Мечникова. - 2012. - т. 4. - № 3. - с. 19-23.

2. Воробьев, Г.И. Неспецифические воспалительные заболевания кишечника/Г.И.Воробьев, И.Л.Халиф // М.: Миклош, 2008. - с. 309.

3. Ивашкин, В.Т. Клинические рекомендации Российской гастроэнтерологической ассоциации и Ассоциации колопроктологов России по диагностике и лечению язвенного колита. / В.Т.Ивашкин, Ю.А.Шелыгин, И.Л.Халиф и соавт. // Колопроктология. - 2013. - № 3 (45) (приложение). - с. 22-34.

4. Халиф, И.Л. Противорецидивная терапия болезни Крона в послеоперационном периоде (обзор литературы). / И.Л.Халиф, А.В.Варданян, М.В.Шапина и соавт. // Колопроктология. - 2017. - № 3 (61). - с. 63.

5. Dignass, A. European Crohn’s and Colitis Organisation [ECCO]. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: current management. / A.Dignass, G.Van Assche, J.O. Lindsay et al. //J. Crohns Colitis. - 2010. - 4. - р. 28-62.

6. Cosnes, J. Impact of the increasing use of immunosuppressants in Crohn’s disease on the need for intestinal surgery. / J.Cosnes, I.Nion-Larmurier, L.Beaugerie et al. // Gut. - 2005. - № 54. - р. 237-241.

7. Chatu, S. The role of thiopurines in reducing the need for surgical resection in Crohn’s disease: a systematic review and meta-analysis. / S.Chatu, V.Subramanian, S.Saxena et al. // Am. J. Gastroenterol. - 2014. - 109. - № 34. - р. 35.

8. Bernell, O. Risk factors for surgery and postoperative recurrence in Crohn’s disease. / O.Bernell, A.Lapidus, G.Hellers. // Ann. Surg. - 2000. - № 231. - р. 38-45.

9. Pascua, M. Meta-analysis: factors predicting postoperative recurrence with placebo therapy in patients with Crohn’s disease. / M.Pascua, C.Su, J.D.Lewis et al. // Aliment Pharmacol. Ther. - 2008. - № 28. -р. 545-56.

10. Freeman, H.J. Natural history and long-term clinical course of Crohn’s disease. / H.J.Freeman. // World J. Gastroenterol. - 2014. - № 20. - р. 31-36.

11. Peyrin-Biroulet, L. Azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in Crohn’s disease: a meta-analysis. / L.Peyrin-Biroulet, P.Deltenre, S.Ardizzone et al. // Am. J. Gastroenterol. - 2009. - № 104. - р. 2089-2096.

12. Jones, G.R. Systematic review: the use of thiopurines or anti-TNF in post-operative Crohn’s disease maintenance-progress and prospects / G.R.Jones, N.A.Kennedy, C.W.Lees et al. //Aliment. Pharmacol. Ther. - 2014. - № 39. - р. 1253-1265.

13. Savarino, E. Adalimumab is more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn’s disease: a randomised controlled trial. // E.Savarino, G.Bodini, P.Dulbecco et al. /Am. J. Gastroenterol. - 2013. -№ 108. - р. 1731-1742.

14. De Cruz, P. Efficacy of thiopurines and adalimumab in preventing Crohn’s disease recurrence in high-risk patients-a POCER study analysis. / P.De Cruz, M.A.Kamm, A.L.Hamilton et al. //Aliment Pharmacol. Ther. - 2015. - № 42. - р. 867-879.

15. Lôpez-Sanroman, A. Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn’s Disease Recurrence. A GETECCU Randomised Trial / A.Lôpez-Sanromân, А.Isabel Vera-Mendoza, А.Eugeni Domènech et al. // Journal of Crohn’s and Colitis. - 2017. - р. 1293-1301.

16. Daperno, M. Development and validation of a new, simplified endoscopic activity score for Crohn’s Disease: the SES-CD. / M.Daperno, G.D’Haens, G.Van Assche// Gastrointest. Endosc. - 2004. - № 60. -р. 505-512.