Long-term efficacy of infliximab combined with seton placement in treatment perianal fistulizing Crohn disease_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Yue , ZHANG Mengci , QIAO Lichao , ZHANG Junbiao , ZHU Ping , CHEN Hongjin , GU Yunfei , YANG Bolin ,  CHEN Yugen

Department of Anorectum, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210000, P. R. China;

Corresponding?author：

CHEN Yugen, Email: chenyg666@126.com

Keywords：

Crohn disease; anal fistula; infliximab; seton placement; long-term efficacy

DOI：

10.7507/1007-9424.201812078

Video：

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Objective To investigate long-term efficacy of infliximab (IFX) combined with seton placement in treatment of perianal fistulizing Crohn disease (CD) and to analyze factors affecting its clinical healing and recurrence.Methods The patients with perianal fistulizing CD underwent the IFX combined with seton placement therapy from July 2010 to January 2017 were collected from the HIS database of the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. The healing and recurrence of perianal fistulizing CD were counted and their influencing factors were analyzed.Results A total of 103 patients with perianal fistulizing CD were included in the study. After a median follow-up of 36 months, 64 patients (62.1%) had a complete fistula healing, 34 patients (33.0%) relapsed. The cumulative recurrence rates of fistula in the 1, 3, and 5 years was 21.8%, 32.6%, and 37.4%, respectively. The multivariate analysis showed that the Montreal classification B1 ［HR=3.987, 95% CI (1.640, 9.694), P=0.023］ and without abscess ［HR=2.724, 95% CI (1.101, 6.740), P=0.030］ were positively associated with the long-term healing of fistula, and the IFX maintenance treatment >3 times ［HR=5.497, 95% CI (1.197, 25.251), P=0.028］ was a risk factor for the recurrence of the fistula.Conclusions Long-term healing rate of fistula by IFX combined with seton placement therapy is higher. Montreal classification B1, without abscess, and IFX maintenance treatment less than 3 times are expected to have a better long-term efficacy.

Citation： LIU Yue, ZHANG Mengci, QIAO Lichao, ZHANG Junbiao, ZHU Ping, CHEN Hongjin, GU Yunfei, YANG Bolin, CHEN Yugen. Long-term efficacy of infliximab combined with seton placement in treatment perianal fistulizing Crohn disease. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(4): 412-417. doi: 10.7507/1007-9424.201812078 Copy

1.	Ng WK, Wong SH, Ng SC. Changing epidemiological trends of inflammatory bowel disease in Asia. Intest Res, 2016, 14(2): 111-119.
2.	李冠煒, 任建安. 重視我國克羅恩病流行病學的研究. 腸外與腸內營養, 2017, 24(3): 135-137.
3.	Molendijk I, Nuij VJ, van der Meulen-de Jong AE, et al. Disappointing durable remission rates in complex Crohn’s disease fistula. Inflamm Bowel Dis, 2014, 20(11): 2022-2028.
4.	Molendijk I, Peeters KC, Baeten CI, et al. Improving the outcome of fistulising Crohn’s disease. Best Pract Res Clin Gastroenterol, 2014, 28(3): 505-518.
5.	de Zoeten EF, Pasternak BA, Mattei P, et al. Diagnosis and treatment of perianal Crohn disease: NASPGHAN clinical report and consensus statement. J Pediatr Gastroenterol Nutr, 2013, 57(3): 401-412.
6.	楊柏霖, 林秋, 陳紅錦, 等. 英夫利昔單抗聯合手術治療克羅恩病肛瘺的臨床療效. 中華胃腸外科雜志, 2013, 16(4): 323-327.
7.	Schwartz DA, Wang A, Ozbay B, et al. Comparison of health care utilization and costs between patients with perianal fistulizing Crohn’s disease treated with biologics with or without previous seton placement. Inflamm Bowel Dis, 2017, 23(10): 1860-1866.
8.	Bouguen G, Siproudhis L, Gizard E, et al. Long-term outcome of perianal fistulizing Crohn’s disease treated with infliximab. Clin Gastroenterol Hepatol, 2013, 11(8): 975-981.
9.	Yassin NA, Askari A, Warusavitarne J, et al. Systematic review: the combined surgical and medical treatment of fistulising perianal Crohn’s disease. Aliment Pharmacol Ther, 2014, 40(7): 741-749.
10.	Topstad DR, Panaccione R, Heine JA, et al. Combined seton placement, infliximab infusion, and maintenance immunosuppressives improve healing rate in fistulizing anorectal Crohn’s disease: a single center experience. Dis Colon Rectum, 2003, 46(5): 577-583.
11.	Talbot C, Sagar PM, Johnston MJ, et al. Infliximab in the surgical management of complex fistulating anal Crohn’s disease. Colorectal Dis, 2005, 7(2): 164-168.
12.	Bell SJ, Williams AB, Wiesel P, et al. The clinical course of fistulating Crohn’s disease. Aliment Pharmacol Ther, 2003, 17(9): 1145-1151.
13.	Schwartz DA, Loftus EV Jr, Tremaine WJ, et al. The natural history of fistulizing Crohn’s disease in Olmsted County, Minnesota. Gastroenterology, 2002, 122(4): 875-880.
14.	Mizrahi N, Wexner SD, Zmora O, et al. Endorectal advancement flap: are there predictors of failure? Dis Colon Rectum, 2002, 45(12): 1616-1621.
15.	Sandborn WJ, Fazio VW, Feagan BG, et al. AGA technical review on perianal Crohn’s disease. Gastroenterology, 2003, 125(5): 1508-1530.
16.	王浩, 徐民民, 竺平, 等. 保留括約肌掛線引流術聯合英夫利昔單抗治療肛周瘺管型克羅恩病的短期臨床療效. 中國普外基礎與臨床雜志, 2017, 24(11): 1380-1383.
17.	van Koperen PJ, Safiruddin F, Bemelman WA, et al. Outcome of surgical treatment for fistula in ano in Crohn’s disease. Br J Surg, 2009, 96(6): 675-679.
18.	Orlando A, Colombo E, Kohn A, et al. Infliximab in the treatment of Crohn’s disease: predictors of response in an Italian multicentric open study. Dig Liver Dis, 2005, 37(8): 577-583.
19.	D’Haens GR, Panaccione R, Higgins PD, et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response? Am J Gastroenterol, 2011, 106(2): 199-212.
20.	Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med, 2004, 350(9): 876-885.
21.	de Groof EJ, Sahami S, Lucas C, et al. Treatment of perianal fistula in Crohn’s disease: a systematic review and meta-analysis comparing seton drainage and anti-tumour necrosis factor treatment. Colorectal Dis, 2016, 18(7): 667-675.
22.	Hotokezaka M, Ikeda T, Uchiyama S, et al. Results of seton drainage and infliximab infusion for complex anal Crohn’s disease. Hepatogastroenterology, 2011, 58(109): 1189-1192.
23.	El-Gazzaz G, Hull T, Church JM. Biological immunomodulators improve the healing rate in surgically treated perianal Crohn’s fistulas. Colorectal Dis, 2012, 14(10): 1217-1223.
24.	Antakia R, Shorthouse AJ, Robinson K, et al. Combined modality treatment for complex fistulating perianal Crohn’s disease. Colorectal Dis, 2013, 15(2): 210-216.
25.	Brochard C, Landemaine A, L’Heritier AM, et al. Anal fistulas in severe perineal Crohn’s disease: MRI assessment in the determination of long-term healing rates. Inflamm Bowel Dis, 2018, 24(7): 1612-1618.
26.	Short SS, Dubinsky MC, Rabizadeh S, et al. Distinct phenotypes of children with perianal perforating Crohn’s disease. J Pediatr Surg, 2013, 48(6): 1301-1305.
27.	Geltzeiler CB, Wieghard N, Tsikitis VL. Recent developments in the surgical management of perianal fistula for Crohn’s disease. Ann Gastroenterol, 2014, 27(4): 320-330.
28.	Tougeron D, Savoye G, Savoye-Collet C, et al. Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn’s disease. Dig Dis Sci, 2009, 54(8): 1746-1752.
29.	Panés J, Rimola J. Perianal fistulizing Crohn’s disease: pathogenesis, diagnosis and therapy. Nat Rev Gastroenterol Hepatol, 2017, 14(11): 652-664.
30.	Gecse KB, Bemelman W, Kamm MA, et al. A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn’s disease. Gut, 2014, 63(9): 1381-1392.
31.	Fields S, Rosainz L, Korelitz BI, et al. Rectal strictures in Crohn’s disease and coexisting perirectal complications. Inflamm Bowel Dis, 2008, 14(1): 29-31.
32.	Jones DW, Finlayson SR. Trends in surgery for Crohn’s disease in the era of infliximab. Ann Surg, 2010, 252(2): 307-312.

1. Ng WK, Wong SH, Ng SC. Changing epidemiological trends of inflammatory bowel disease in Asia. Intest Res, 2016, 14(2): 111-119.
2. 李冠煒, 任建安. 重視我國克羅恩病流行病學的研究. 腸外與腸內營養, 2017, 24(3): 135-137.
3. Molendijk I, Nuij VJ, van der Meulen-de Jong AE, et al. Disappointing durable remission rates in complex Crohn’s disease fistula. Inflamm Bowel Dis, 2014, 20(11): 2022-2028.
4. Molendijk I, Peeters KC, Baeten CI, et al. Improving the outcome of fistulising Crohn’s disease. Best Pract Res Clin Gastroenterol, 2014, 28(3): 505-518.
5. de Zoeten EF, Pasternak BA, Mattei P, et al. Diagnosis and treatment of perianal Crohn disease: NASPGHAN clinical report and consensus statement. J Pediatr Gastroenterol Nutr, 2013, 57(3): 401-412.
6. 楊柏霖, 林秋, 陳紅錦, 等. 英夫利昔單抗聯合手術治療克羅恩病肛瘺的臨床療效. 中華胃腸外科雜志, 2013, 16(4): 323-327.
7. Schwartz DA, Wang A, Ozbay B, et al. Comparison of health care utilization and costs between patients with perianal fistulizing Crohn’s disease treated with biologics with or without previous seton placement. Inflamm Bowel Dis, 2017, 23(10): 1860-1866.
8. Bouguen G, Siproudhis L, Gizard E, et al. Long-term outcome of perianal fistulizing Crohn’s disease treated with infliximab. Clin Gastroenterol Hepatol, 2013, 11(8): 975-981.
9. Yassin NA, Askari A, Warusavitarne J, et al. Systematic review: the combined surgical and medical treatment of fistulising perianal Crohn’s disease. Aliment Pharmacol Ther, 2014, 40(7): 741-749.
10. Topstad DR, Panaccione R, Heine JA, et al. Combined seton placement, infliximab infusion, and maintenance immunosuppressives improve healing rate in fistulizing anorectal Crohn’s disease: a single center experience. Dis Colon Rectum, 2003, 46(5): 577-583.
11. Talbot C, Sagar PM, Johnston MJ, et al. Infliximab in the surgical management of complex fistulating anal Crohn’s disease. Colorectal Dis, 2005, 7(2): 164-168.
12. Bell SJ, Williams AB, Wiesel P, et al. The clinical course of fistulating Crohn’s disease. Aliment Pharmacol Ther, 2003, 17(9): 1145-1151.
13. Schwartz DA, Loftus EV Jr, Tremaine WJ, et al. The natural history of fistulizing Crohn’s disease in Olmsted County, Minnesota. Gastroenterology, 2002, 122(4): 875-880.
14. Mizrahi N, Wexner SD, Zmora O, et al. Endorectal advancement flap: are there predictors of failure? Dis Colon Rectum, 2002, 45(12): 1616-1621.
15. Sandborn WJ, Fazio VW, Feagan BG, et al. AGA technical review on perianal Crohn’s disease. Gastroenterology, 2003, 125(5): 1508-1530.
16. 王浩, 徐民民, 竺平, 等. 保留括約肌掛線引流術聯合英夫利昔單抗治療肛周瘺管型克羅恩病的短期臨床療效. 中國普外基礎與臨床雜志, 2017, 24(11): 1380-1383.
17. van Koperen PJ, Safiruddin F, Bemelman WA, et al. Outcome of surgical treatment for fistula in ano in Crohn’s disease. Br J Surg, 2009, 96(6): 675-679.
18. Orlando A, Colombo E, Kohn A, et al. Infliximab in the treatment of Crohn’s disease: predictors of response in an Italian multicentric open study. Dig Liver Dis, 2005, 37(8): 577-583.
19. D’Haens GR, Panaccione R, Higgins PD, et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response? Am J Gastroenterol, 2011, 106(2): 199-212.
20. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med, 2004, 350(9): 876-885.
21. de Groof EJ, Sahami S, Lucas C, et al. Treatment of perianal fistula in Crohn’s disease: a systematic review and meta-analysis comparing seton drainage and anti-tumour necrosis factor treatment. Colorectal Dis, 2016, 18(7): 667-675.
22. Hotokezaka M, Ikeda T, Uchiyama S, et al. Results of seton drainage and infliximab infusion for complex anal Crohn’s disease. Hepatogastroenterology, 2011, 58(109): 1189-1192.
23. El-Gazzaz G, Hull T, Church JM. Biological immunomodulators improve the healing rate in surgically treated perianal Crohn’s fistulas. Colorectal Dis, 2012, 14(10): 1217-1223.
24. Antakia R, Shorthouse AJ, Robinson K, et al. Combined modality treatment for complex fistulating perianal Crohn’s disease. Colorectal Dis, 2013, 15(2): 210-216.
25. Brochard C, Landemaine A, L’Heritier AM, et al. Anal fistulas in severe perineal Crohn’s disease: MRI assessment in the determination of long-term healing rates. Inflamm Bowel Dis, 2018, 24(7): 1612-1618.
26. Short SS, Dubinsky MC, Rabizadeh S, et al. Distinct phenotypes of children with perianal perforating Crohn’s disease. J Pediatr Surg, 2013, 48(6): 1301-1305.
27. Geltzeiler CB, Wieghard N, Tsikitis VL. Recent developments in the surgical management of perianal fistula for Crohn’s disease. Ann Gastroenterol, 2014, 27(4): 320-330.
28. Tougeron D, Savoye G, Savoye-Collet C, et al. Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn’s disease. Dig Dis Sci, 2009, 54(8): 1746-1752.
29. Panés J, Rimola J. Perianal fistulizing Crohn’s disease: pathogenesis, diagnosis and therapy. Nat Rev Gastroenterol Hepatol, 2017, 14(11): 652-664.
30. Gecse KB, Bemelman W, Kamm MA, et al. A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn’s disease. Gut, 2014, 63(9): 1381-1392.
31. Fields S, Rosainz L, Korelitz BI, et al. Rectal strictures in Crohn’s disease and coexisting perirectal complications. Inflamm Bowel Dis, 2008, 14(1): 29-31.
32. Jones DW, Finlayson SR. Trends in surgery for Crohn’s disease in the era of infliximab. Ann Surg, 2010, 252(2): 307-312.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Long-term efficacy of infliximab combined with seton placement in treatment perianal fistulizing Crohn disease

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