Local injection of infliximab in severe fistulating perianal Crohn’s disease: an open uncontrolled study
Tóm tắt
Perianal fistulas are frequent complications of Crohn’s disease. Intravenous infliximab can control perianal disease and promote perianal fistula closure. Perifistular infliximab injections have been proposed for patients who are intolerant or unresponsive to intravenous therapy. The aim of this study was to assess the long-term efficacy of surgical treatment combined with local infliximab therapy. A prospective cohort study was designed. Twelve patients with Crohn’s disease and high/complex transphincteric and intrasphincteric perianal fistulas refractory to other treatment were submitted to core-out fistulectomies, plus perifistular injections of infliximab (20–25 mg in 15–20 ml of 5% glucose) every 4–6 weeks. The main outcome measure was the clinical closure of all perianal fistulas. A 95% confidence interval was calculated for short- and long-term fistula closure rates. None of the procedures were associated with local or systemic adverse effects. Four patients did not complete treatment, two because of relapse of intestinal symptoms, which required intravenous infliximab. In one case, treatment with intravenous infliximab was complicated by a hypersensitivity reaction. Eight patients continued treatment until all perianal fistulas were closed and setons were removed (median: 5 sessions). Persistent closure was observed in seven (87.5%, 95% CI: 47.4–99.6) of the eight patients 12 months after completion of treatment and in five (62.5%; 95% CI: 24.5–91.5) of eight at the end of follow-up (range: 19–43 months, median: 35 months). The cohort we examined is small, but fistulectomy combined with repeated perifistular injections of infliximab appears to be safe and may help in fistula healing. However, in most patients, permanent closure of all fistulas is not achieved.
Tài liệu tham khảo
Schwartz DA, Loftus EV, Tremaine WJ et al (2002) The natural history of fistulizing Crohn’s disease in Olmsted County, Minnesota. Gastroenterology 122:875–880
Sandborn WJ, Fazio VW, Feagan BG, Hanauer SB (2003) AGA technical review on perianal Crohn’s disease. Gastroenterology 125:1508–1530
Fichera A, McCormack R, Rubin MA, Hurst RD, Michelassi F (2005) Long-term outcome of surgically treated Crohn’s colitis: a prospective study. Dis Colon Rectum 48:936–939
Wise PE, Schwartz DA (2006) Management of perianal Crohn’s disease. Clin Gastroenterol Hepatol 4:426–430
Buchmann P, Keighley MR, Allan RN, Thompson H, Alexander-Williams J (1980) Natural history of perianal Crohn’s disease. Ten year follow-up: a plea for conservatism. Am J Surg 140:642–644
Williamson PR, Helllinger MD, Larach SW, Ferrara A (1995) Twenty-year review of the surgical management of perianal Crohn’s disease. Dis Colon Rectum 38:389–392
Present DH, Rutgeerts P, Targan S et al (1980) Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Eng J Med 340:1398–1405
Lichtiger S (2010) Healing of perianal fistulae by local injection of antibody to TNF. Gastroenterology 120:A3154
Poggioli G, Laureti S, Pierangeli F et al (2005) Local injection of infliximab for the treatment of perianal Crohn’s disease. Dis Colon Rectum 48:768–774
Asteria CR, Ficari F, Bagnoli S, Milla M, Tonelli F (2006) Treatment of perianal fistulas in Crohn’s disease by local injection of antibody to TNF-alpha accounts for a favourable response in selected cases: a pilot study. Scand J Gastroenterol 41:1064–1072
Parks AG, Gordon PH, Hardcastle JD (1976) A classification of fistula-in-ano. Br J Surg 63:1–12
Pikarsky AJ, Gervaz P, Wexner SD (2002) Perianal Crohn’s disease: a new scoring system to evaluate and predict outcome of surgical intervention. Arch Surg 137:774–778
Sands BE, Anderson FH, Bernstein CN et al (2004) Infliximab maintenance therapy for fistulizing Crohn’s disease. N Eng J Med 350:876–885
Carter MJ, Lobo AJ, Travis SPL (2004) Guidelines for the management of inflammatory bowel disease in adults. Gut 53:V1–V16
Dignass A, Van Assche G, Lindsay JO et al (2010) The second European evidence based consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis 4:28–62
Regueiro M, Mardini H (2003) Treatment of perianal fistulising Crohn’s disease with infliximab alone or as an adjunct to examen under anesthesia with seton placement. Inflamm Bowel Dis 9:98–103
Hyder SA, Travis SP, Jewell DP, Mortensen NJ, George BD (2006) Fistulating anal Crohn’s disease: results of combined surgical and infliximab treatment. Dis Colon Rectum 49:1837–1841
Topstad DR, Panaccione R, Heine JA, Johnson DR, MacLean AR, Buie WD (2003) Combined seton placement, infliximab infusion, and maintenance immunosuppressives improve healing rate in fistulising anorectal Crohn’s disease: a single centre experience. Dis Colon Rectum 46:577–583
Hanauer SB (1999) Review article: safety of Infliximab in clinical trials. Aliment Pharmacol Ther 4:16–22
Keane J, Gershon S, Wise RP et al (2001) Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. New Eng J Med 345:1098–1104
Poggioli G, Laureti S, Pierangeli F et al (2010) Local injection of adalimumab for perianal Crohn’s disease: better than infliximab? Inflamm Bowel Dis 16:1631
Taxonera C, Schwartz DA, Garcia-Olmo D (2009) Emerging treatments for complex perianal fistula in Crohn’s disease. World J Gastroenterol 15:4263–4272