Treatment of perianal fistulas in Crohn’s disease - review of literature and current recommendations
DOI:
https://doi.org/10.12775/QS.2023.12.01.003Keywords
Crohn, perianal fistula, biological treatment, IBSAbstract
Introduction: Crohn's disease is an idiopathic inflammatory disorder of unknown etiology, associated with genetic, immunological, and environmental factors. The incidence of this disease continues to rise in developed countries. In almost 25% of patients, perianal fistulas occur during the course of the disease, which are difficult to treat and significantly impair the patient's quality of life.
Aim of the study: To summarize the current state of knowledge on the treatment of Crohn's disease with perianal fistulas, with a particular focus on biological therapies and stem cell treatments.
Methods and Materials: A systemic review was conducted using PubMed, Google Scholar, and ScienceDirect databases and it was limited to studies published in last 5 years. The search strategy was based on following terms: "Crohn's disease", "perianal fistula", "biological treatment", and "inflammatory bowel disease".
Results: In recent years, there has been intensive research into new treatment options for perianal fistulas in Crohn's disease. Infliximab remains the first-line therapy, best controlled by monitoring the drug concentration in the serum. Alternatively, other drugs such as ustekinumab and vedolizumab may be considered. The combination of biological and surgical treatment is a recognized standard of care and modern, minimally invasive techniques that preserve sphincters, such as the FiLaC™ laser procedure, are increasingly being used. A novel and very promising therapeutic approach is based on mesenchymal stem cells, which may offer hope for patients who do not improve with standard treatment.
Conclusion: Perianal disease in patients with Crohn's disease poses a significant therapeutic challenge and has a substantial negative impact on the physical and emotional well-being of patients. Despite the existence of various therapeutic options, a certain percentage of patients still fails to achieve clinical remission. Further research into new therapies is necessary.
References
Agrawal M, Jess T. Implications of the changing epidemiology of inflammatory bowel disease in a changing world. United European Gastroenterol J. 2022 Dec;10(10):1113-1120. doi: 10.1002/ueg2.12317. Epub 2022 Oct 17. PMID: 36251359; PMCID: PMC9752308.
Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2018 Apr;113(4):481-517. doi: 10.1038/ajg.2018.27. Epub 2018 Mar 27. Erratum in: Am J Gastroenterol. 2018 Jul;113(7):1101. PMID: 29610508.
Luglio G, Tropeano FP, Pagano G, Cricrì M. Editorial: Abdominal and Perianal Fistulizing Crohn's Disease: Imaging, Surgical Techniques and Basic Research. Front Surg. 2022 Jun 28;9:952874. doi: 10.3389/fsurg.2022.952874. PMID: 35836609; PMCID: PMC9273927.
Atia O, Focht G, Lujan R, Ledder O, Greenfeld S, Kariv R, Dotan I, Yanai H, Gabay H, Balicer R, Haklai Z, Nevo D, Turner D. Perianal Crohn Disease Is More Common in Children and Is Associated With Complicated Disease Course Despite Higher Utilization of Biologics: A Population-based Study From The epidemiology group of the Israeli IBD Research Nucleus (epiIIRN). J Pediatr Gastroenterol Nutr. 2022 Jun 1;74(6):788-793. doi: 10.1097/MPG.0000000000003422. Epub 2022 Feb 22. PMID: 35192577.
Tsai L, McCurdy JD, Ma C, Jairath V, Singh S. Epidemiology and Natural History of Perianal Crohn's Disease: A Systematic Review and Meta-Analysis of Population-Based Cohorts. Inflamm Bowel Dis. 2022 Oct 3;28(10):1477-1484. doi: 10.1093/ibd/izab287. PMID: 34792604; PMCID: PMC9527611.
McGregor CGC, Tandon R, Simmons A. Pathogenesis of Fistulating Crohn's Disease: A Review. Cell Mol Gastroenterol Hepatol. 2023;15(1):1-11. doi: 10.1016/j.jcmgh.2022.09.011. Epub 2022 Sep 29. PMID: 36184031; PMCID: PMC9667304.
Ranasinghe IR, Hsu R. Crohn Disease. 2023 Feb 20. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 28613792.
Zulqarnain M, Deepak P, Yarur AJ. Therapeutic Drug Monitoring in Perianal Fistulizing Crohn's Disease. J Clin Med. 2022 Mar 25;11(7):1813. doi: 10.3390/jcm11071813. PMID: 35407421; PMCID: PMC8999746.
Sun XL, Chen SY, Tao SS, Qiao LC, Chen HJ, Yang BL. Optimized timing of using infliximab in perianal fistulizing Crohn's disease. World J Gastroenterol. 2020 Apr 14;26(14):1554-1563. doi: 10.3748/wjg.v26.i14.1554. PMID: 32327905; PMCID: PMC7167413.
Shehab M, Alrashed F, Heron V, Restellini S, Bessissow T. Comparative Efficacy of Biologic Therapies for Inducing Response and Remission in Fistulizing Crohn's Disease: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. Inflamm Bowel Dis. 2023 Mar 1;29(3):367-375. doi: 10.1093/ibd/izac103. PMID: 35604382.
Wetwittayakhlang P, Al Khoury A, Hahn GD, Lakatos PL. The Optimal Management of Fistulizing Crohn's Disease: Evidence beyond Randomized Clinical Trials. J Clin Med. 2022 May 28;11(11):3045. doi: 10.3390/jcm11113045. PMID: 35683433; PMCID: PMC9181669.
Ayoub F, Odenwald M, Micic D, Dalal SR, Pekow J, Cohen RD, Rubin DT, Sakuraba A. Vedolizumab for perianal fistulizing Crohn's disease: systematic review and meta-analysis. Intest Res. 2022 Apr;20(2):240-250. doi: 10.5217/ir.2021.00091. Epub 2022 Feb 8. PMID: 35124951; PMCID: PMC9081994.
Attauabi M, Burisch J, Seidelin JB. Efficacy of ustekinumab for active perianal fistulizing Crohn's disease: a systematic review and meta-analysis of the current literature. Scand J Gastroenterol. 2021 Jan;56(1):53-58. doi: 10.1080/00365521.2020.1854848. Epub 2020 Dec 2. PMID: 33264569.
Schwartz DA, Peyrin-Biroulet L, Lasch K, Adsul S, Danese S. Efficacy and Safety of 2 Vedolizumab Intravenous Regimens for Perianal Fistulizing Crohn's Disease: ENTERPRISE Study. Clin Gastroenterol Hepatol. 2022 May;20(5):1059-1067.e9. doi: 10.1016/j.cgh.2021.09.028. Epub 2021 Sep 29. PMID: 34597729.
Yao J, Zhang H, Su T, Peng X, Zhao J, Liu T, Wang W, Hu P, Zhi M, Zhang M. Ustekinumab Promotes Radiological Fistula Healing in Perianal Fistulizing Crohn's Disease: A Retrospective Real-World Analysis. J Clin Med. 2023 Jan 25;12(3):939. doi: 10.3390/jcm12030939. PMID: 36769587; PMCID: PMC9917613.
Newman KL, Johnson LA, Stidham RW, Higgins PDR. Vedolizumab more likely to be discontinued than ustekinumab in anti-TNF-experienced patients with fistulizing Crohn's disease. Therap Adv Gastroenterol. 2023 Mar 3;16:17562848221148254. doi: 10.1177/17562848221148254. PMID: 36895282; PMCID: PMC9989393.
Croitoru DO, Seigel K, Nathanielsz N, Elsawi R, Silverberg MS, Piguet V, Sibbald C. Treatment of severe hidradenitis Suppurativa and Fistulizing Crohn's disease with Guselkumab. J Eur Acad Dermatol Venereol. 2022 Jul;36(7):e563-e565. doi: 10.1111/jdv.18033. Epub 2022 Mar 8. PMID: 35224787.
Berman HS, Villa NM, Shi VY, Hsiao JL. Guselkumab in the treatment of concomitant hidradenitis suppurativa, psoriasis, and Crohn's disease. J Dermatolog Treat. 2021 Mar;32(2):261-263. doi: 10.1080/09546634.2019.1654067. Epub 2019 Aug 25. PMID: 31389737.
Meima-van Praag EM, van Rijn KL, Wasmann KATGM, Snijder HJ, Stoker J, D'Haens GR, Gecse KB, Gerhards MF, Jansen JM, Dijkgraaf MGW, van der Bilt JDW, Mundt MW, Spinelli A, Danese S, Bemelman WA, Buskens CJ. Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn's disease (PISA-II): a patient preference randomised trial. Lancet Gastroenterol Hepatol. 2022 Jul;7(7):617-626. doi: 10.1016/S2468-1253(22)00088-7. Epub 2022 Apr 12. Erratum in: Lancet Gastroenterol Hepatol. 2022 Jul;7(7):600. PMID: 35427495.
Luglio G, Tropeano FP, Pagano G, Cricrì M. Editorial: Abdominal and Perianal Fistulizing Crohn's Disease: Imaging, Surgical Techniques and Basic Research. Front Surg. 2022 Jun 28;9:952874. doi: 10.3389/fsurg.2022.952874. PMID: 35836609; PMCID: PMC9273927.
Gklavas A, Sotirova I, Karageorgou M, Kozonis T, Poulaki A, Papaconstantinou I. Is the Quality of Life of Patients with Fistulizing Perianal Crohn' s Disease Impaired by the Presence of Chronic Loose, Non-cutting Seton? J Gastrointest Surg. 2021 Oct;25(10):2686-2689. doi: 10.1007/s11605-021-04987-2. Epub 2021 Mar 26. PMID: 33772403.
Angriman I, Tomassi M, Ruffolo C, Bordignon G, Saadeh L, Gruppo M, Pucciarelli S, Bardini R, Scarpa M. Impact on Quality of Life of Seton Placing in Perianal Crohn's Disease. Front Surg. 2022 Jan 24;8:806497. doi: 10.3389/fsurg.2021.806497. PMID: 35141271; PMCID: PMC8818691.
Chirurgia po Dyplomie→2020→02→Przetoki odbytu – co nowego w diagnostyce i leczeniu.
Jimenez M, Mandava N. Anorectal Fistula. 2023 Feb 2. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32809492.
Wolicki A, Jäger P, Deska T, Senkal M. Sphincter-saving therapy for fistula-in-ano: long-term follow-up after FiLaC®. Tech Coloproctol. 2021 Feb;25(2):177-184. doi: 10.1007/s10151-020-02332-4. Epub 2020 Aug 31. PMID: 32865716.
Cao D, Li W, Ji Y, Wang X, Cui Z. Efficacy and safety of FiLaC™ for perianal fistulizing Crohn's disease: a systematic review and meta-analysis. Tech Coloproctol. 2022 Oct;26(10):775-781. doi: 10.1007/s10151-022-02682-1. Epub 2022 Aug 12. PMID: 35962294.
Sluckin TC, Gispen WH, Jongenotter J, Hazen SJA, Smeets S, van der Bilt JDW, Smeenk RM, Schouten R. Treatment of cryptoglandular fistulas with the fistula tract laser closure (FiLaC™) method in comparison with standard methods: first results of a multicenter retrospective comparative study in the Netherlands. Tech Coloproctol. 2022 Oct;26(10):797-803. doi: 10.1007/s10151-022-02644-7. Epub 2022 Jun 24. PMID: 35749023.
Meng ZW, Baumgart DC. Darvadstrocel for the treatment of perianal fistulas in Crohn's disease. Expert Rev Gastroenterol Hepatol. 2020 Jun;14(6):405-410. doi: 10.1080/17474124.2020.1764349. Epub 2020 May 20. PMID: 32354239.
Panés J, García-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. 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 Sep 24;388(10051):1281-90. doi: 10.1016/S0140-6736(16)31203-X. Epub 2016 Jul 29. PMID: 27477896.
Furukawa S, Mizushima T, Nakaya R, Shibata M, Yamaguchi T, Watanabe K, Futami K. Darvadstrocel for complex perianal fistulas in Japanese adults with Crohn's disease: a phase 3 study. J Crohns Colitis. 2022 Sep 23:jjac144. doi: 10.1093/ecco-jcc/jjac144. Epub ahead of print. PMID: 36149832.
Fathallah N, Akaffou M, Haouari MA, Spindler L, Alam A, Barré A, Pommaret E, Fels A, de Parades V. Deep remission improves the quality of life of patients with Crohn's disease and anoperineal fistula treated with darvadstrocel: results of a French pilot study. Tech Coloproctol. 2023 Feb 22. doi: 10.1007/s10151-023-02765-7. Epub ahead of print. PMID: 36811811.
Panés J, Bouma G, Ferrante M, Kucharzik T, Nachury M, de la Portilla de Juan F, Reinisch W, Selvaggi F, Tschmelitsch J, Brett NR, Ladouceur M, Binek M, Hantsbarger G, Campbell-Hill S, Karki C, Buskens C. INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn's Disease Treated in the ADMIRE-CD Trial. Inflamm Bowel Dis. 2022 Nov 2;28(11):1737-1745. doi: 10.1093/ibd/izab361. PMID: 35099555; PMCID: PMC9629463.
. Flacs M, Collard M, Doblas S, Zappa M, Cazals-Hatem D, Maggiori L, Panis Y, Treton X, Ogier-Denis E. Preclinical Model of Perianal Fistulizing Crohn's Disease. Inflamm Bowel Dis. 2020 Apr 11;26(5):687-696. doi: 10.1093/ibd/izz288. PMID: 31774918.
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Copyright (c) 2023 Dominik Szawica, Aleksandra Kuźniar, Kamila Fularska, Michał Oleszko, Edward Wąsiewicz, Radosław Bernacki, Piotr Bernacki, Martyna Dutka, Witold Zardzewiały
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