The aim of this intervention study is to determine whether long-term infliximab therapy can decrease the proctectomy rate in patients with failed total colectomy and ileorectal anastomosis (IRA) for Crohn’s disease (CD). Twelve patients (5 females) – with a median age of 36.6 years (range 18–56 years), previously treated with IRA (5 in our institution and 7 referred) for colorectal and perianal CD (median Crohn’s Disease Activity Index 334.5, range 220–426), with rectal disease recurrence requiring proctectomy, no responders to conventional therapy but infliximab-naïve – were treated with infliximab infusions (Remicade™ 5 mg/kg at 0, 2, 6 weeks and then every 8 weeks) to avoid proctectomy. The main outcome measures consisted of IRA preservation and bowel function at study end. Mortality and major adverse reactions have not been observed. At the time of the median follow-up (57.4 months, range 36–92), the rectum was preserved in 10 patients (83.3%). One patient underwent proctectomy 6 weeks after the beginning of the treatment for unresponsiveness to drugs and another after 26 weeks for rectal stenosis. Anorectal function (maximum tolerated volume: 239 ± 43 vs. 294 ± 36 ml) and quality of life (Inflammatory Bowel Disease Questionnaire score 89.2 ± 20.6 vs. 173.8 ± 31.9) improved, and the Wexner Continence score (4.4 ± 2.4 vs. 1.7 ± 1.0) and daily defecations (5.2 ± 1.03 vs. 2.7 ± 1.05) decreased in 10 patients. Our results, although preliminary, are encouraging and seem to justify a less aggressive approach in patients with rectal and perianal recurrence after IRA for CD.

Keywords:
Infliximab, Rectal sparing, Ileorectal anastomosis, Crohnߣs disease, Quality of life
1.
Farmer RG, Hawk WA, Turnbull RB Jr: Clinical patterns in Crohn’s disease: a statistical study of 615 cases. Gastroenterology 1975;68:627–635.
2.
Lockhart-Mummery HE: Crohn’s disease: anal lesions. Dis Colon Rectum 1973;18:200.
3.
Lennard-Jones JE, Ritchie JK, Zohrab WJ: Proctocolitis and Crohn’s disease of the colon: a comparison of the clinical course. Gut 1976;17:477–482.
4.
Wolff BG, Culp CE, Beart RW Jr, Ilstrup DM, Ready RL: Anorectal Crohn’s disease. A long-term perspective. Dis Colon Rectum 1985;28:709–711.
5.
Williams JG, Wong WD, Rothenberger DA, Goldberg SM: Recurrence of Crohn’s disease after resection. Br J Surg 1991;78:10–19.
6.
Tekkis PP, Purkayastha S, Lanitis S, Athanasiou T, Heriot AG, Orchard TR, Nicholls RJ, Darzi AW: A comparison of segmental vs. subtotal/total colectomy for colonic Crohn’s disease: a meta-analysis. Colorectal Dis 2006;8:82–90.
7.
Topstad DR, Panaccione R, Heine JA, Johnson DR, MacLean AR, Buie WD: 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;46:577–583.
8.
Present DH, Rutgeers P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, Podolsky DK, Sands BE, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ: Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Eng J Med 1999;340:1398–1405.
9.
Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P, ACCENT I Study Group: Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002;359:1541–1549.
10.
Scribano ML, Prantera C: Review article: medical treatment of active Crohn’s disease. Aliment Farmacol Ther 2002;16:35–39.
11.
Rizzello F, Gionchetti P, Venturi A, Morselli C, Campieri M: Review article: the management of refractory Crohn’s disease. Aliment Farmacol Ther 2002;16:40–47.
12.
Sandborn WJ, Fazio VW, Feagan BG, Hanauer SB, American Gastroenterological Association Clinical Practice Committee: AGA technical review on perianal Crohn’s disease. Gastroenterology 2003;125:1508–1530.
13.
Hyder SA, Travis SPL, Jewell DP, McC Mortensen NJ, George BD: Fistulating anal Crohn’s disease: results of combined surgical and infliximab treatment. Dis Colon Rectum 2006;49:1837–1841.
14.
Vermeire S, Noman M, Van Assche G, Baert F, D’Haens G, Rutgeerts P: Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut 2007;56:1226–1231.
15.
Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ: Infliximab maintenance therapy for fistulising Crohn’s disease. N Engl J Med 2004;350:876–885.
16.
Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I, Van Assche G, Hoffman I, Van Steen K, Vermeire S, Rutgeerts P: Long-term outcome of treatment with infliximab in 614 Crohn’s disease patients: results from a single centre cohort. Gut 2009;58:492–500.
17.
Fidder HH, Schnitzler F, Ferrante M, Norman M, Katsanos K, Segaert S, Van Assche G, Vermeire S, Rutgeerts P: Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single center cohort study. Gut 2009;58:501–508.
18.
Guyatt G, Mitchell A, Irvine EJ, Singer J, Williams N, Goodacre R, Tompkins C: A new measure of health status for clinical trials in inflammatory bowel disease. Gastroenterology 1989;96:804–810.
19.
Buchmann P, Waterman IT, Keighley MRB, et al: The prognosis of ileorectal anastomosis in Crohn’s disease. Br J Surg 1981;68:7–10.
20.
Ambrose NS, Keighley MR, Alexander-Williams J, Allan RN: Clinical impact of colectomy and ileorectal anastomosis in the management of Crohn’s disease. Gut 1984;25:223–227.
21.
Longo WE, Oakley JR, Lavery IC, Church JM, Fazio VW: Outcome of ileorectal anastomosis for Crohn’s colitis. Dis Colon Rectum 1992;35:1066–1071.
22.
Rieger N, Collopy B, Fink R, Mackay J, Woods R, Keck J: Total colectomy for Crohn’s disease. Aust NZ J Surg 1999;69:28–30.
23.
Yamamoto T, Keighley MRB: Fate of the rectum and ileal recurrence rates after total colectomy for Crohn’s disease. World J Surg 2002;24:125–129.
24.
Cattan P, Bonhomme N, Panis Y, Lémann M, Coffin B, Bouhnik Y, Allez M, Sarfati E, Valleur P: Fate of the rectum in patients undergoing total colectomy for Crohn’s disease. Br J Surg 2002;89:454–459.
25.
Elton C, Makin G, Hitos K, Cohen CR: Mortality, morbidity and functional outcome after ileorectal anastomosis. Br J Surg 2003;90:59–65.
26.
Keighley MR, Buchmann P, Lee JR: Assessment of anorectal function in selection of patients for ileorectal anastomosis in Crohn’s colitis. Gut 1982;23:102–107.
27.
Weaver RM, Keighley MR: Measurement of rectal capacity in the assessment of patients for colectomy and ileorectal anastomosis in Crohn’s colitis. Dis Colon Rectum 1986;29:443–445.
28.
Mortensen NJ, Ritchie JK, Hawley PR, Todd IP, Lennard-Jones JE: Surgery for acute Crohn’s colitis: results and long-term follow-up. Br J Surg 1984;71:783–784.
29.
Sorrentino D, Terrosu G, Avellini C, Beltrami CA, Bresadola V, Toso F: Prevention of postoperative recurrence of Crohn’s disease by infliximab. Eur J Gastroenterol Hepatol 2006;18:457–459.
30.
Rutgeerts P, D’Haens G, Targan S: Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology 1999;117:761–769.
31.
Sands B, Van Deventer S, Bernstein C: Long-term treatment of fistulising Crohn’s disease: response to infliximab in the ACCENT II trial through 54 weeks (abstract). Gastroenterology 2002;122:A81.
32.
Poritz LS, Rowe WA, Koltun WA: Remicade does not abolish the need for surgery in fistulising Crohn’s disease. Dis Colon Rectum 2002;45:771–775.
33.
Regueiro M, Mardini H: Treatment of perianal fistulising Crohn’s disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis 2003;9:98–103.
34.
Rutgeerts P, Van Assche G, Vermeire S: Review article: infliximab therapy for inflammatory bowel disease-seven years on. Aliment Pharmacol Ther 2006;23:451–463.
35.
Rubenstein JH, Chong RY, Cohen RD: Infliximab decreases resource use among patients with Crohn’s disease. J Clin Gastroenterol 2002;35:151–156.
36.
Hanauer S, Schreiber S, Bao W, Bala M, Keenan G, Olson A, Rutgeerts P: ACCENT I trial: infliximab response rates over 30 weeks. Am J Gastroenterol 2001;96:S302.
37.
Sorrentino D, Terrosu G, Avellini C, Maiero S: Infliximab with low-dose methotrexate for prevention of postsurgical recurrence of ileocolonic Crohn disease. Arch Intern Med 2007;167:1804–1807.
38.
Cassinotti A, Travis S: Incidence and clinical significance of immunogenicity to infliximab in Crohn’s disease: a critical systematic review. Inflamm Bowel Dis 2009;15:1264–1275.
© 2011 S. Karger AG, Basel
2011
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.