Surgical closure, mainly with glue injection and anti-tumour necrosis factor α, in fistulizing perianal Crohn's disease: A multicentre randomized controlled trial

Laurent Abramowitz, Charlène Brochard, François Pigot, Pauline Roumeguere, Hélène Pillant, Béatrice Vinson Bonnet, Jean Luc Faucheron, Agnès Senéjoux, Guillaume Bonnaud, Guillaume Meurette, Jean Marie Fayette, Cécile Train, Ghislain Staumont, Laurent Siproudhis, Dominique Bouchard, Laurent Abramowitz, Charlène Brochard, François Pigot, Pauline Roumeguere, Hélène Pillant, Béatrice Vinson Bonnet, Jean Luc Faucheron, Agnès Senéjoux, Guillaume Bonnaud, Guillaume Meurette, Jean Marie Fayette, Cécile Train, Ghislain Staumont, Laurent Siproudhis, Dominique Bouchard

Abstract

Aim: In patients with fistulizing perianal Crohn's disease (CD), the need for a secondary surgical step is not defined. The aim was to assess the efficacy of surgical closure compared to a single seton removal in patients with drained fistulizing perianal CD treated with adalimumab.

Methods: This was a multicentre, randomized controlled trial, comparing seton removal + surgical closure (closure group) to seton removal alone (control group) with a stratification according to the American Gastroenterological Association classification. The primary end-point was fistula closure at month 12 defined by the association of the following criteria: no seton, absence of a visible external opening, absence of discharge from the tract after finger compression, absence of an internal opening, absence of perianal pain/abscess and absence of fistula-related abnormalities.

Results: Among the 64 included patients (262 expected) (48 complex fistula, 75%), 33 were randomized to the closure group and 31 to the control group. In the closure group, 26 patients (78.8%) had glue. At month 12, overall fistula closure was achieved in 35 of the evaluable 58 patients (60%): 18/32 (56%) in the surgery group and 17/26 (65%) in the control group (P = 0.479). In the closure group, fistula closure was observed in 13/25 (52%) and 5/7 (71%) patients with complex and simple fistula respectively (P = 0.426), compared with 12/18 (67%) and 5/8 (63%), respectively in the control group (P = 1.000).

Conclusions: Seton removal alone seems to be no more effective than a secondary surgical step (in particular glue injection) in patients having fistulizing perianal CD controlled by an initial drainage combined with adalimumab. The results should be interpreted with caution.

Trial registration: ClinicalTrials.gov NCT01388257.

Keywords: Crohn's disease; fistulizing perianal; seton removal; surgical closure.

© 2021 Association of Coloproctology of Great Britain and Ireland.

References

REFERENCES

    1. Park SH, Aniwan S, Scott Harmsen W, Tremaine WJ, Lightner AL, Faubion WA, et al. Update on the natural course of fistulizing perianal Crohn’s disease in a population-based cohort. Inflamm Bowel Dis. 2019;25:1054-60.
    1. Kasparek MS, Glatzle J, Temeltcheva T, Mueller MH, Koenigsrainer A, Kreis ME. Long-term quality of life in patients with Crohn’s disease and perianal fistulas: influence of fecal diversion. Dis Colon Rectum. 2007;50:2067-74.
    1. Mahadev S, Young JM, Selby W, Solomon MJ. Self-reported depressive symptoms and suicidal feelings in perianal Crohn’s disease. Colorectal Dis. 2012;14:331-5.
    1. Mahadev S, Young JM, Selby W, Solomon MJ. Quality of life in perianal Crohn’s disease: what do patients consider important? Dis Colon Rectum. 2011;54:579-85.
    1. Ingle SB, Loftus EV. The natural history of perianal Crohn’s disease. Dig Liver Dis. 2007;39:963-9.
    1. Linares L, Moreira LF, Andrews H, Allan RN, Alexander-Williams J, Keighley MR. Natural history and treatment of anorectal strictures complicating Crohn’s disease. Br J Surg. 1988;75:653-5.
    1. Brochard C, Siproudhis L, Wallenhorst T, Cuen D, d'Halluin PN, Garros A, et al. Anorectal stricture in 102 patients with Crohn’s disease: natural history in the era of biologics. Aliment Pharmacol Ther. 2014;40:796-803.
    1. Schwartz DA, Ghazi LJ, Regueiro M, Fichera A, Zoccali M, Ong EMW, et al. Guidelines for the multidisciplinary management of Crohn’s perianal fistulas: summary statement. Inflamm Bowel Dis. 2015;21:723-30.
    1. Panes J, Bouhnik Y, Reinisch W, Stoker J, Taylor SA, Baumgart DC, et al. Imaging techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based consensus guidelines. J Crohns Colitis. 2013;7:556-85.
    1. Bouguen G, Siproudhis L, Gizard E, Wallenhorst T, Billioud V, Bretagne J, et al. Long-term outcome of perianal fistulizing Crohn’s disease treated with infliximab. Clin Gastroenterol Hepatol. 2013;11(8):975-81.e4.
    1. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999;340:1398-405.
    1. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350:876-85.
    1. Colombel J, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132:52-65.
    1. Senéjoux A, Siproudhis L, Abramowitz L, Munoz-Bongrand N, Desseaux K, Bouguen G, et al. Fistula plug in fistulising ano-perineal Crohn’s disease: a randomised controlled trial. J Crohns Colitis. 2016;10:141-8.
    1. Grimaud J, Munoz-Bongrand N, Siproudhis L, Abramowitz L, Sénéjoux A, Vitton V, et al. Fibrin glue is effective healing perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2010;138(2275-81):2281.e1.
    1. Panés J, García-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2018;154:1334-1342.e4.
    1. Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: Diagnosis and medical management. J Crohns Colitis. 2017;11:3-25.
    1. Gecse KB, Bemelman W, Kamm MA, Stoker J, Khanna R, Ng SC, et al. A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn’s disease. Gut. 2014;63:1381-92.
    1. Irvine EJ. Usual therapy improves perianal Crohn’s disease as measured by a new disease activity index. McMaster IBD Study Group. J Clin Gastroenterol. 1995;20:27-32.
    1. Guyatt G, Mitchell A, Irvine EJan, Singer J, Williams N, Goodacre R, et al. A new measure of health status for clinical trials in inflammatory bowel disease. Gastroenterology. 1989;96:804-10.
    1. Vaizey CJ, Carapeti E, Cahill JA, Kamm MA. Prospective comparison of faecal incontinence grading systems. Gut. 1999;44:77-80.
    1. Assche G, Vanbeckevoort D, Bielen D, Coremans G, Aerden I, Noman M, et al. Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn’s disease. Am J Gastroenterol. 2003;98:332-9.
    1. Wasmann KA, de Groof EJ, Stellingwerf ME, D’Haens GR, Ponsioen CY, Gecse KB, et al. Treatment of perianal fistulas in Crohn’s disease, seton versus anti-TNF versus surgical closure following anti-TNF [PISA]: a randomised controlled trial. J Crohns Colitis. 2020;14:1049-56.
    1. Bouchard D, Abramowitz L, Bouguen G, Brochard C, Dabadie A, de Parades V, et al. Anoperineal lesions in Crohn’s disease: French recommendations for clinical practice. Tech Coloproctol. 2017;21:683-91.
    1. Vidon M, Munoz-Bongrand N, Lambert J, Maggiori L, Zeitoun JD, Corte H, et al. Long-term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease. Colorectal Dis. 2021;23:894-900.
    1. Yassin NA, Askari A, Warusavitarne J, Faiz OD, Athanasiou T, Phillips RKS, et al. Systematic review: the combined surgical and medical treatment of fistulising perianal Crohn’s disease. Aliment Pharmacol Ther. 2014;40:741-9.
    1. de Groof EJ, Sahami S, Lucas C, Ponsioen CY, Bemelman WA, Buskens CJ. 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;18:667-75.
    1. Adegbola SO, Sahnan K, Tozer PJ, Strouhal R, Hart AL, Lung PFC, et al. Symptom amelioration in Crohn's perianal fistulas using video-assisted anal fistula treatment (VAAFT). J Crohns Colitis. 2018;12:1067-72.
    1. Siegmund B, Feakins RM, Bamias G, Ludvig JC, Teixeira FV, Rogler G, et al. Results of the fifth scientific workshop of the ECCO (II): pathophysiology of perianal fistulizing disease. J Crohns Colitis. 2016;10:377-86.
    1. Brochard C, Landemaine A, L’Heritier AM, Dewitte MP, Tchoundjeu B, Rohou T, et al. Anal fistulas in severe perineal Crohn’s disease: MRI assessment in the determination of long-term healing rates. Inflamm Bowel Dis. 2018;24:1612-8.
    1. Tozer P, Ng SC, Siddiqui MR, Plamondon S, Burling D, Gupta A, et al. Long-term MRI-guided combined anti-TNF-alpha and thiopurine therapy for Crohn's perianal fistulas. Inflamm Bowel Dis. 2012;18(10):1825-34.
    1. Bothwell LE, Greene JA, Podolsky SH, Jones DS. Assessing the gold standard-lessons from the history of RCTs. N Engl J Med. 2016;374:2175-81.

Source: PubMed

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