[en] Stricturing subocclusive small bowel Crohn's disease (CD) is often an indication for surgery. We embarked on an open label pilot study to assess the safety and efficacy of infliximab in patients with stricturing subocclusive CD. Patients and methods : A cohort of patients with a documented and symptomatic small bowel stricture caused by CD was studied. Patients had to be refractory to corticosteroids and/or immunosuppressives, and not in need for immediate surgery. The patients were treated by a single infusion of infliximab 5 mg/kg and followed up at w1, w2, w4 and w8. Results : After the 6(th) patients, the study was prematurely discontinued because the predefined safety thresholds of more than 2 surgeries within the first 5 patients was reached. Only two patients completed the 8 weeks study, with a positive response to infliximab and improvement of inflammation confirmed by the CRP and CT scan. Two patients had to be operated early and the last two patients first did well but worsened after one month and were operated 35 and 42 days after infliximab, respectively. No surgical complications occurred in the 4 operated patients. In conclusion, a subset of patients with subocclusive small bowel stricturing CD may benefit from infliximab.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Boverie, Jacques ; Centre Hospitalier Universitaire de Liège - CHU > Imagerie médicale
Dewit, Olivier
Baert, Filip
De Vos, M.
D'Haens, G.
Language :
English
Title :
Treatment of small bowel subocclusive Crohn's disease with infliximab: an open pilot study
LOUIS E., COLLARD A., OGER A.F., DE GROTE E., EL YAFI F., BELAICHE J. Behaviour of Crohn's disease according to the Vienna classification : changing pattern over the course of the disease. Gut, 2001, 49 : 777-782.
GRAHAM M.F., DIEGELMANN R.F., ELSON CO. et al. Collagen content and types in the intestinal strictures of Crohn's disease. Gastroenterology, 1988, 94 : 257-265.
BROOKER J.C., BECKETT C.G., SAUNDERS B.P., BENSON M.J. Long-acting steroid injection after endoscopic dilation of anastomotic Crohn's strictures may improve the outcome : a retrospective case series. Endoscopy, 2003, 35 : 333-337.
LOUIS E., MICHEL V., HUGOT J.P. et al. Early development of stricturing or penetrating pattern in Crohn's disease is influenced by disease location, number of flares, and smoking but not by NOD2/CARD15 genotype. Gut, 2003, 52: 552-557.
AGRAWAL A., DURRANI S., LEIPER K., ELLIS A., MORRIS A.I., RHODES J. Effect of systemic corticosteroid therapy on risk for intra-abdominal or pelvic abscess in non-operated Crohn's disease. Clin. Gastroenterol and Hepatol., 2005, 3 : 1215-1220.
VASSALO R., MATTESON E., THOMAS C.F. Jr. Clinical response of rheumatoid arthritis-associated pulmonary fibrosis to TNF alpha inhibition. Chest, 2002, 122 : 1093-1096.
NAKAZATO H., OKU H., YAMANE S., TSURUTA Y., SUZUKI R. A novel anti-fibrotic agent pirfenidone suppresses TNF alpha at the translational level. J. Immunol., 2002, 169 : 929-936.
THEISS A.L., SIMMONS J.G., JOBIN C., LUND P.K. Tumor necrosis factor (TNF) alpha increases collagen accumulation and proliferation in intestinal myofibroblasts via TNF receptor 2. J. Biol. Chem., 2005, 280 : 36099-36109.
XU X., RIVKIND A., PIKARSKY A., PAPPO O., BISCHOFF S.C., LEVISCHAFFER F. Mast cells and eosinophils have a potential profibrogenic role in Crohn disease. Scand. J. Gastroenterol., 2004, 39 : 440-447.
TARGAN S., HANAUER S., VAN DEVENTER S. et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N. Engl. J. Med., 1997, 337 : 1029-1035.
HANAUER S., FEAGAN B., LICHTENSTEIN G. et al. Maintenance infliximab for Crohn's disease : the ACCENT I randomised trial. Lancet, 2002, 359 : 1541-1549.
HOLTMANN M., WANITSCHKE R., HELISCH A., BARTENSTEIN P., GALLE P.R., NEURATH M. Anti-TNF antibodies in the treatment of inflammatory intestinal stenoses in Crohn's disease. Z. Gastroenterol., 2003, 41 : 11-17.
SORRENTINO D., AVELLINI C., BELTRAMI C.A., PASQUAL E., ZEARO E. Selective effect of infliximab on the inflammatory component of a colonic stricture in Crohn's disease. Int. J. Colorectal. Dis., 2006, 21: 276-281.
PRAJAPATI et al. Symptomatic luminal stricture underlies infliximab non-response in Crohn's disease. Gastroenterology, 2002, 122 : A777.
BELAICHE J., LOUIS E. Early obstructive colon after treatment of active refractory Crohn's disease with infliximab. Gastroenterol. Clin. Biol., 2003, 27 : 1045-1047.
LICHTENSTEIN G.R., OLSON A., TRAVIS S. et al. Factors associated with the development of intestinal strictures or obstructions in patients with Crohn's disease. Am. J. Gastroenterol., 2006, 101 : 1030-1038.
FELDER J.B., ADLER D.J., KORELITZ B.I. The safety of corticosteroid therapy in Crohn's disease with an abdominal mass. Am. J. Gastroenterol., 1991, 86 : 1450-1455.
COLOMBEL J.F., LOFTUS E., TREMAINE W. et al. Early postoperative complications are not increased in patients with Crohn's disease treated peri-operatively with infliximab or immunosuppressive therapy. Am. J. Gastroenterol., 2004, 99 : 878-883.
MARCHAL L., D'HAENS G., VAN ASSCHE G. et al. The risk of post-operative complications associated with infliximab therapy for Crohn's disease : a controlled cohort study. Aliment Pharmacol. Ther., 2004, 19 : 749-54.