514
Views
27
CrossRef citations to date
0
Altmetric
Review

Recent advances in the management of perianal fistulizing Crohn’s disease: lessons for the clinic

, &
Pages 563-577 | Received 02 Jan 2019, Accepted 15 Apr 2019, Published online: 26 Apr 2019

References

  • Kappelman MD, Moore KR, Allen JK, et al. Recent trends in the prevalence of Crohn‘s disease and ulcerative colitis in a commercially insured US population. Dig Dis Sci. 2013;58(2):519–525.
  • 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.
  • Lichtenstein GR, Loftus EV, Isaacs KL, et al. ACG Clinical Guideline: management of Crohn‘s Disease in Adults. Am J Gastroenterol. 2018;113(4):481–517.
  • Eglinton TW, Barclay ML, Gearry RB, et al. The spectrum of perianal Crohn‘s disease in a population-based cohort. Dis Colon Rectum. 2012;55(7):773–777.
  • 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.
  • Loffler T, Welsch T, Muhl S, et al. Long-term success rate after surgical treatment of anorectal and rectovaginal fistulas in Crohn‘s disease. Int J Colorectal Dis. 2009;24(5):521–526.
  • Beaugerie L, Seksik P, Nion-Larmurier I, et al. Predictors of Crohn‘s disease. Gastroenterology. 2006;130(3):650–656.
  • Bell SJ, Williams AB, Wiesel P, et al. The clinical course of fistulating Crohn‘s disease. Aliment Pharmacol Ther. 2003;17(9):1145–1151.
  • Pittet V, Juillerat P, Michetti P, et al. Appropriateness of therapy for fistulizing Crohn‘s disease: findings from a national inflammatory bowel disease cohort. Aliment Pharmacol Ther. 2010;32(8):1007–1016.
  • 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.
  • Bemelman WA, Warusavitarne J, Sampietro GM, et al. ECCO-ESCP consensus on surgery for Crohn‘s disease. J Crohns Colitis. 2018;12(1):1–16.
  • Makowiec F, Jehle EC, Starlinger M. Clinical course of perianal fistulas in Crohn‘s disease. Gut. 1995;37(5):696–701.
  • Sandborn WJ, Fazio VW, Feagan BG, et al. American gastroenterological association clinical practice C. AGA technical review on perianal Crohn‘s disease. Gastroenterology. 2003;125(5):1508–1530.
  • Aguilera-Castro L, Ferre-Aracil C, Garcia-Garcia-de-Paredes A, et al. Management of complex perianal Crohn‘s disease. Ann Gastroenterol. 2017;30(1):33–44.
  • Tsui JJ, Huynh HQ. Is top-down therapy a more effective alternative to conventional step-up therapy for Crohn‘s disease? Ann Gastroenterol. 2018;31(4):413–424.
  • Van Deventer SJ. Tumour necrosis factor and Crohn‘s disease. Gut. 1997;40(4):443–448.
  • Chowers Y, Allez M. Efficacy of anti-TNF in Crohn‘s disease: how does it work? Curr Drug Targets. 2010;11(2):138–142.
  • Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn‘s disease. N Engl J Med. 1999;340(18):1398–1405.
  • 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.
  • Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn‘s disease. N Engl J Med. 2010;362(15):1383–1395.
  • 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):975–981e971–974.
  • West RL, van der Woude CJ, Hansen BE, et al. Clinical and endosonographic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn‘s disease with infliximab: a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2004;20(11–12):1329–1336.
  • Schwartz DA, Ghazi LJ, Regueiro M. Guidelines for medical treatment of Crohn‘s perianal fistulas: critical evaluation of therapeutic trials. Inflamm Bowel Dis. 2015;21(4):737–752.
  • Dewint P, Hansen BE, Verhey E, et al. Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn‘s disease: a randomised, double-blind, placebo controlled trial (ADAFI). Gut. 2014;63(2):292–299.
  • Yarur AJ, Kanagala V, Stein DJ, et al. Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn‘s disease. Aliment Pharmacol Ther. 2017;45(7):933–940.
  • El-Matary W, Walters TD, Huynh HQ, et al. Higher postinduction infliximab serum trough levels are associated with healing of fistulizing perianal Crohn‘s disease in children. Journal of Crohn's and Colitis. 2018;12(supplement_1):S380-S381.
  • Davidov Y, Ungar B, Bar-Yoseph H, et al. Association of induction infliximab levels with clinical response in perianal Crohn‘s disease. J Crohns Colitis. 2017;11(5):549–555.
  • Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn‘s disease: the CLASSIC-I trial. Gastroenterology. 2006;130(2):323–333; quiz 591.
  • Sandborn WJ, Rutgeerts P, Enns R, et al. Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med. 2007;146(12):829–838.
  • Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn‘s disease: the CHARM trial. Gastroenterology. 2007;132(1):52–65.
  • Colombel JF, Da S, Sandborn WJ, et al. Adalimumab for the treatment of fistulas in patients with Crohn‘s disease. Gut. 2009;58(7):940–948.
  • Lichtiger S, Binion DG, Wolf DC, et al. The CHOICE trial: adalimumab demonstrates safety, fistula healing, improved quality of life and increased work productivity in patients with Crohn‘s disease who failed prior infliximab therapy. Aliment Pharmacol Ther. 2010;32(10):1228–1239.
  • Yu H, MacIsaac D, Wong JJ, et al. Market share and costs of biologic therapies for inflammatory bowel disease in the USA. Aliment Pharmacol Ther. 2018;47(3):364–370.
  • Cohen RD. The pharmacoeconomics of biologic therapy for IBD. Nat Rev Gastroenterol Hepatol. 2010;7(2):103–109.
  • Dejaco C, Harrer M, Waldhoer T, et al. Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn‘s disease. Aliment Pharmacol Ther. 2003;18(11–12):1113–1120.
  • Present DH, Korelitz BI, Wisch N, et al. Treatment of Crohn‘s disease with 6-mercaptopurine. A long-term, randomized, double-blind study. N Engl J Med. 1980;302(18):981–987.
  • Pearson DC, May GR, Fick GH, et al. Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. Ann Intern Med. 1995;123(2):132–142.
  • Chande N, Townsend CM, Parker CE, et al. Azathioprine or 6-mercaptopurine for induction of remission in Crohn‘s disease. Cochrane Database Syst Rev. 2016;10:CD000545.
  • Sandborn WJ, Present DH, Isaacs KL, et al. Tacrolimus for the treatment of fistulas in patients with Crohn‘s disease: a randomized, placebo-controlled trial. Gastroenterology. 2003;125(2):380–388.
  • Present DH, Lichtiger S. Efficacy of cyclosporine in treatment of fistula of Crohn‘s disease. Dig Dis Sci. 1994;39(2):374–380.
  • Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn‘s disease. N Engl J Med. 2007;357(3):228–238.
  • Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn‘s disease. N Engl J Med. 2007;357(3):239–250.
  • Schreiber S, Lawrance IC, Thomsen OO, et al. Randomised clinical trial: certolizumab pegol for fistulas in Crohn‘s disease - subgroup results from a placebo-controlled study. Aliment Pharmacol Ther. 2011;33(2):185–193.
  • Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn‘s disease. N Engl J Med. 2013;369(8):711–721.
  • Feagan BG, Schwartz DA, Danese S, et al. Efficacy of vedolizumab in fistulising Crohn‘s disease: exploratory analyses of data from GEMINI 2. J Crohns Colitis. 2018;12(5):621–626.
  • Khorrami S, Ginard D, Marin-Jimenez I, et al. Ustekinumab for the treatment of refractory Crohn‘s disease: the spanish experience in a large multicentre open-label cohort. Inflamm Bowel Dis. 2016;22(7):1662–1669.
  • Ma C, Fedorak RN, Kaplan GG, et al. Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn‘s disease: real world experience from a multicentre cohort. Aliment Pharmacol Ther. 2017;45(9):1232–1243.
  • Sands BE, Gasink C, Jacobstein D, et al. Fistula healing in pivotal studies of ustekinumab in Crohn’s disease. Gastroenterology. 2017;152(5):S185.
  • Nielsen OH, Munck LK. Drug insight: aminosalicylates for the treatment of IBD. Nat Clin Pract Gastroenterol Hepatol. 2007;4(3):160–170.
  • 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.
  • 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.
  • Regueiro M, Mardini H. Treatment of perianal fistulizing Crohn‘s disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis. 2003;9(2):98–103.
  • 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.
  • Hyder SA, Travis SP, Jewell DP, et al. Fistulating anal Crohn‘s disease: results of combined surgical and infliximab treatment. Dis Colon Rectum. 2006;49(12):1837–1841.
  • Ritchie RD, Sackier JM, Hodde JP. Incontinence rates after cutting seton treatment for anal fistula. Colorectal Dis. 2009;11(6):564–571.
  • Gaertner WB, Decanini A, Mellgren A, et al. Does infliximab infusion impact results of operative treatment for Crohn‘s perianal fistulas? Dis Colon Rectum. 2007;50(11):1754–1760.
  • Tanaka S, Matsuo K, Sasaki T, et al. Clinical advantages of combined seton placement and infliximab maintenance therapy for perianal fistulizing Crohn‘s disease: when and how were the seton drains removed? Hepatogastroenterology. 2010;57(97):3–7.
  • Lee MJ, Heywood N, Adegbola S, et al. Systematic review of surgical interventions for Crohn‘s anal fistula. BJS Open. 2017;1(3):55–66.
  • 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.
  • Joo JS, Weiss EG, Nogueras JJ, et al. Endorectal advancement flap in perianal Crohn‘s disease. Am Surg. 1998;64(2):147–150.
  • Marchesa P, Hull TL, Fazio VW. Advancement sleeve flaps for treatment of severe perianal Crohn‘s disease. Br J Surg. 1998;85(12):1695–1698.
  • Soltani A, Kaiser AM. Endorectal advancement flap for cryptoglandular or Crohn‘s fistula-in-ano. Dis Colon Rectum. 2010;53(4):486–495.
  • O‘Riordan JM, Datta I, Johnston C, et al. A systematic review of the anal fistula plug for patients with Crohn‘s and non-Crohn‘s related fistula-in-ano. Dis Colon Rectum. 2012;55(3):351–358.
  • Nasseri Y, Cassella L, Berns M, et al. The anal fistula plug in Crohn‘s disease patients with fistula-in-ano: a systematic review. Colorectal Dis. 2016;18(4):351–356.
  • Senejoux A, Siproudhis L, Abramowitz L, et al. Fistula plug in fistulising ano-perineal Crohn‘s disease: a randomised controlled trial. J Crohns Colitis. 2016;10(2):141–148.
  • Lindsey I, Smilgin-Humphreys MM, Cunningham C, et al. A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula. Dis Colon Rectum. 2002;45(12):1608–1615.
  • Grimaud JC, Munoz-Bongrand N, Siproudhis L, et al. Fibrin glue is effective healing perianal fistulas in patients with Crohn‘s disease. Gastroenterology. 2010;138(7):2275–2281, 2281 e2271.
  • Singer NG, Caplan AI. Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol. 2011;6:457–478.
  • DelaRosa O, Dalemans W, Lombardo E. Mesenchymal stem cells as therapeutic agents of inflammatory and autoimmune diseases. Curr Opin Biotechnol. 2012;23(6):978–983.
  • Gazdic M, Volarevic V, Arsenijevic N, et al. Mesenchymal stem cells: a friend or foe in immune-mediated diseases. Stem Cell Rev. 2015;11(2):280–287.
  • Garcia-Olmo D, Garcia-Arranz M, Herreros D, et al. A phase I clinical trial of the treatment of Crohn‘s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005;48(7):1416–1423.
  • Garcia-Olmo D, Herreros D, Pascual I, et al. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum. 2009;52(1):79–86.
  • Panes J, Garcia-Olmo D, Van Assche G, et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn‘s disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016;388(10051):1281–1290.
  • Panes J, Garcia-Olmo D, Van Assche G, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn‘s disease. Gastroenterology. 2018;154(5):1334–1342 e1334.
  • Lightner AL, Wang Z, Zubair AC, et al. A systematic review and meta-analysis of mesenchymal stem cell injections for the treatment of perianal crohn‘s disease: progress made and future directions. Dis Colon Rectum. 2018;61(5):629–640.
  • Bermejo F, Guerra I, Algaba A, et al. Pharmacological approach to the management of Crohn‘s disease patients with perianal disease. Drugs. 2018;78(1):1–18.
  • Bor R, Fabian A, Farkas K, et al. Human mesenchymal stem cell therapy in the management of luminal and perianal fistulizing Crohn‘s disease - review of pathomechanism and existing clinical data. Expert Opin Biol Ther. 2018;18(7):737–745.
  • Dailey FE, Turse EP, Naseer M, et al. Review of stem cells as promising therapy for perianal disease in inflammatory bowel disease. World J Transplant. 2018;8(4):97–101.
  • Gingold DS, Murrell ZA, Fleshner PR. A prospective evaluation of the ligation of the intersphincteric tract procedure for complex anal fistula in patients with Crohn‘s disease. Ann Surg. 2014;260(6):1057–1061.
  • Kaminski JP, Zaghiyan K, Fleshner P. Increasing experience of ligation of the intersphincteric fistula tract for patients with Crohn‘s disease: what have we learned? Colorectal Dis. 2017;19(8):750–755.
  • Adegbola SO, Sahnan K, Tozer PJ, et al. Review of local injection of anti-TNF for perianal fistulising Crohn‘s disease. Int J Colorectal Dis. 2017;32(11):1539–1544.
  • Schwandner O. Video-assisted anal fistula treatment (VAAFT) combined with advancement flap repair in Crohn‘s disease. Tech Coloproctol. 2013;17(2):221–225.
  • Adegbola SO, Sahnan K, Tozer PJ, et al. Symptom amelioration in Crohn‘s perianal fistulas using video assisted anal fistula treatment (VAAFT). J Crohns Colitis. 2018.
  • Wilhelm A, Fiebig A, Krawczak M. Five years of experience with the FiLaC laser for fistula-in-ano management: long-term follow-up from a single institution. Tech Coloproctol. 2017;21(4):269–276.
  • Mueller MH, Geis M, Glatzle J, et al. Risk of fecal diversion in complicated perianal Crohn‘s disease. J Gastrointest Surg. 2007;11(4):529–537.
  • Singh S, Ding NS, Mathis KL, et al. Systematic review with meta-analysis: faecal diversion for management of perianal Crohn‘s disease. Aliment Pharmacol Ther. 2015;42(7):783–792.
  • Sahnan K, Tozer PJ, Adegbola SO, et al. Developing a core outcome set for fistulising perianal Crohn‘s disease. Gut. 2019;68(2):226–238.
  • Huff-Hardy K, Bedair M, Vazquez R, et al. Efficacy of combination vedolizumab and ustekinumab for refractory Crohn‘s disease. Inflamm Bowel Dis. 2017;23(10):E49.
  • de Groof EJ, Buskens CJ, Ponsioen CY, et al. Multimodal treatment of perianal fistulas in Crohn‘s disease: seton versus anti-TNF versus advancement plasty (PISA): study protocol for a randomized controlled trial. Trials. 2015;16:366.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.