Infliximab for the Treatment of Fistulas in Patients with Crohn's Disease
Daniel H. Present, M.D., Paul Rutgeerts, M.D., Stephan Targan, M.D., Stephen B. Hanauer, M.D., Lloyd Mayer, M.D., R.A. van Hogezand, M.D., Daniel K. Podolsky, M.D., Bruce E. Sands, M.D., Tanja Braakman, M.D., Kimberly L. DeWoody, Ph.D., Thomas F. Schaible, Ph.D., and Sander J.H. van Deventer, M.D., Ph.D.
Background Enterocutaneous fistulas are a serious complicationof Crohn's disease and are difficult to treat. Infliximab, achimeric monoclonal antibody to tumor necrosis factor , hasrecently been developed as a treatment for Crohn's disease.We conducted a randomized, multicenter, double-blind, placebo-controlledtrial of infliximab for the treatment of fistulas in patientswith Crohn's disease.
Methods The study included 94 adult patients who had drainingabdominal or perianal fistulas of at least three months' durationas a complication of Crohn's disease. Patients were randomlyassigned to receive one of three treatments: placebo (31 patients),5 mg of infliximab per kilogram of body weight (31 patients),or 10 mg of infliximab per kilogram (32 patients); all threewere to be administered intravenously at weeks 0, 2, and 6.The primary end point was a reduction of 50 percent or morefrom base line in the number of draining fistulas observed attwo or more consecutive study visits. A secondary end pointwas the closure of all fistulas.
Results Sixty-eight percent of the patients who received 5 mgof infliximab per kilogram and 56 percent of those who received10 mg per kilogram achieved the primary end point, as comparedwith 26 percent of the patients in the placebo group (P=0.002and P=0.02, respectively). In addition, 55 percent of the patientsassigned to receive 5 mg of infliximab per kilogram and 38 percentof those assigned to 10 mg per kilogram had closure of all fistulas,as compared with 13 percent of the patients assigned to placebo(P=0.001 and P=0.04, respectively). The median length of timeduring which the fistulas remained closed was three months.More than 60 percent of patients in all the groups had adverseevents. For patients treated with infliximab, the most commonwere headache, abscess, upper respiratory tract infection, andfatigue.
Conclusions Infliximab is an efficacious treatment for fistulasin patients with Crohn's disease.
Source Information
From Mount Sinai Medical Center, New York (D.H.P., L.M.); University Hospital, Leuven, Belgium (P.R.); Cedars Sinai Medical Center, Los Angeles (S.T.); the University of Chicago, Chicago (S.B.H.); Leiden University Medical Center, Leiden, the Netherlands (R.A.H.); the Gastrointestinal Unit and Center for Inflammatory Bowel Diseases, Massachusetts General Hospital and Harvard Medical School, Boston (D.K.P., B.E.S.); Centocor, Malvern, Pa. (T.B., K.L.D., T.F.S.); and the Academic Medical Center, Amsterdam (S.J.H.D.). Other participants in the study are listed in the Appendix.
Address reprint requests to Dr. Present at 12 E. 86th St., New York, NY 10028-0517.
Akobeng, A K
(2008). Crohn's disease: current treatment options. Arch. Dis. Child.
93: 787-792
[Abstract][Full Text]
Grunewald, J., Tsao, M.-L., Perera, R., Dong, L., Niessen, F., Wen, B. G., Kubitz, D. M., Smider, V. V., Ruf, W., Nasoff, M., Lerner, R. A., Schultz, P. G.
(2008). Immunochemical termination of self-tolerance. Proc. Natl. Acad. Sci. USA
105: 11276-11280
[Abstract][Full Text]
Sandborn, W J, Hanauer, S B, Rutgeerts, P, Fedorak, R N, Lukas, M, MacIntosh, D G, Panaccione, R, Wolf, D, Kent, J D, Bittle, B, Li, J, Pollack, P F
(2007). Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial. Gut
56: 1232-1239
[Abstract][Full Text]
Sandborn, W. J., Feagan, B. G., Stoinov, S., Honiball, P. J., Rutgeerts, P., Mason, D., Bloomfield, R., Schreiber, S., the PRECISE 1 Study Investigators,
(2007). Certolizumab Pegol for the Treatment of Crohn's Disease. NEJM
357: 228-238
[Abstract][Full Text]
Johnston, S. L
(2007). Biologic therapies: what and when?. J. Clin. Pathol.
60: 8-17
[Abstract][Full Text]
Huugen, D., Cohen Tervaert, J. W., Heeringa, P.
(2006). TNF-{alpha} Bioactivity-Inhibiting Therapy in ANCA-Associated Vasculitis: Clinical and Experimental Considerations. CJASN
1: 1100-1107
[Abstract][Full Text]
Feldmann, M., Pusey, C. D.
(2006). Is There a Role for TNF-{alpha} in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis? Lessons from Other Chronic Inflammatory Diseases. J. Am. Soc. Nephrol.
17: 1243-1252
[Abstract][Full Text]
Monk, J. P., Phillips, G., Waite, R., Kuhn, J., Schaaf, L. J., Otterson, G. A., Guttridge, D., Rhoades, C., Shah, M., Criswell, T., Caligiuri, M. A., Villalona-Calero, M. A.
(2006). Assessment of Tumor Necrosis Factor Alpha Blockade As an Intervention to Improve Tolerability of Dose-Intensive Chemotherapy in Cancer Patients. JCO
24: 1852-1859
[Abstract][Full Text]
Halligan, S., Stoker, J.
(2006). Imaging of fistula in ano.. Radiology
239: 18-33
[Abstract][Full Text]
Brooklyn, T N, Dunnill, M G S, Shetty, A, Bowden, J J, Williams, J D L, Griffiths, C E M, Forbes, A, Greenwood, R, Probert, C S
(2006). Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut
55: 505-509
[Abstract][Full Text]
Podolsky, D. K., Gonzalez, R. G., Hasserjian, R. P.
(2006). Case records of the Massachusetts General Hospital. Case 8-2006. A 71-year-old woman with Crohn's disease and altered mental status.. NEJM
354: 1178-1184
[Full Text]
Caprilli, R, Gassull, M A, Escher, J C, Moser, G, Munkholm, P, Forbes, A, Hommes, D W, Lochs, H, Angelucci, E, Cocco, A, Vucelic, B, Hildebrand, H, Kolacek, S, Riis, L, Lukas, M, de Franchis, R, Hamilton, M, Jantschek, G, Michetti, P, O'Morain, C, Anwar, M M, Freitas, J L, Mouzas, I A, Baert, F, Mitchell, R, Hawkey, C J, for the European Crohn's and Colitis Organisation,
(2006). European evidence based consensus on the diagnosis and management of Crohn's disease: special situations. Gut
55: i36-i58
[Abstract][Full Text]
Biancone, L, Orlando, A, Kohn, A, Colombo, E, Sostegni, R, Angelucci, E, Rizzello, F, Castiglione, F, Benazzato, L, Papi, C, Meucci, G, Riegler, G, Petruzziello, C, Mocciaro, F, Geremia, A, Calabrese, E, Cottone, M, Pallone, F
(2006). Infliximab and newly diagnosed neoplasia in Crohn's disease: a multicentre matched pair study. Gut
55: 228-233
[Abstract][Full Text]
Bodily, K. D., Fletcher, J. G., Solem, C. A., Johnson, C. D., Fidler, J. L., Barlow, J. M., Bruesewitz, M. R., McCollough, C. H., Sandborn, W. J., Loftus, E. V. Jr, Harmsen, W. S., Crownhart, B. S.
(2006). Crohn Disease: Mural Attenuation and Thickness at Contrast-enhanced CT Enterography--Correlation with Endoscopic and Histologic Findings of Inflammation. Radiology
238: 505-516
[Abstract][Full Text]
Rutgeerts, P., Sandborn, W. J., Feagan, B. G., Reinisch, W., Olson, A., Johanns, J., Travers, S., Rachmilewitz, D., Hanauer, S. B., Lichtenstein, G. R., de Villiers, W. J.S., Present, D., Sands, B. E., Colombel, J. F.
(2005). Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis. NEJM
353: 2462-2476
[Abstract][Full Text]
Franchimont, D., Roland, S., Gustot, T., Quertinmont, E., Toubouti, Y., Gervy, M.-C., Deviere, J., Van Gossum, A.
(2005). Impact of Infliximab on Serum Leptin Levels in Patients with Crohn's Disease. J. Clin. Endocrinol. Metab.
90: 3510-3516
[Abstract][Full Text]
Orenstein, R., Kolls, J. K., Zhang, Z., Mannon, P. J., Fuss, I. J., Strober, W.
(2005). Anti-Interleukin-12 Antibody for Active Crohn's Disease. NEJM
352: 627-628
[Full Text]
The Wegener's Granulomatosis Etanercept Trial (WGE,
(2005). Etanercept plus Standard Therapy for Wegener's Granulomatosis. NEJM
352: 351-361
[Abstract][Full Text]
Kitamura, K., Nakamoto, Y., Kaneko, S., Mukaida, N.
(2004). Pivotal roles of interleukin-6 in transmural inflammation in murine T cell transfer colitis. J. Leukoc. Biol.
76: 1111-1117
[Abstract][Full Text]
Generini, S, Giacomelli, R, Fedi, R, Fulminis, A, Pignone, A, Frieri, G, Del Rosso, A, Viscido, A, Galletti, B, Fazzi, M, Tonelli, F, Matucci-Cerinic, M
(2004). Infliximab in spondyloarthropathy associated with Crohn's disease: an open study on the efficacy of inducing and maintaining remission of musculoskeletal and gut manifestations. Ann Rheum Dis
63: 1664-1669
[Abstract][Full Text]
Singh, S. M., Rau, N. V., Cohen, L. B., Harris, H.
(2004). Cutaneous nocardiosis complicating management of Crohn's disease with infliximab and prednisone. CMAJ
171: 1063-1064
[Abstract][Full Text]
Sandborn, W J, Feagan, B G, Radford-Smith, G, Kovacs, A, Enns, R, Innes, A, Patel, J
(2004). CDP571, a humanised monoclonal antibody to tumour necrosis factor {alpha}, for moderate to severe Crohn's disease: a randomised, double blind, placebo controlled trial. Gut
53: 1485-1493
[Abstract][Full Text]
Askari, F. K., Dick, R., Mao, M., Brewer, G. J.
(2004). Tetrathiomolybdate Therapy Protects Against Concanavalin A and Carbon Tetrachloride Hepatic Damage in Mice. Exp. Biol. Med.
229: 857-863
[Abstract][Full Text]
Matsuoka, K, Inoue, N, Sato, T, Okamoto, S, Hisamatsu, T, Kishi, Y, Sakuraba, A, Hitotsumatsu, O, Ogata, H, Koganei, K, Fukushima, T, Kanai, T, Watanabe, M, Ishii, H, Hibi, T
(2004). T-bet upregulation and subsequent interleukin 12 stimulation are essential for induction of Th1 mediated immunopathology in Crohn's disease. Gut
53: 1303-1308
[Abstract][Full Text]
Bataille, F, Klebl, F, Rummele, P, Schroeder, J, Farkas, S, Wild, P-J, Furst, A, Hofstadter, F, Scholmerich, J, Herfarth, H, Rogler, G
(2004). Morphological characterisation of Crohn's disease fistulae. Gut
53: 1314-1321
[Abstract][Full Text]
Sandborn, W J, Faubion, W A
(2004). Biologics in inflammatory bowel disease: how much progress have we made?. Gut
53: 1366-1373
[Full Text]
Carter, M J, Lobo, A J, Travis, S P L
(2004). Guidelines for the management of inflammatory bowel disease in adults. Gut
53: v1-v16
[Full Text]
Couriel, D., Saliba, R., Hicks, K., Ippoliti, C., de Lima, M., Hosing, C., Khouri, I., Andersson, B., Gajewski, J., Donato, M., Anderlini, P., Kontoyiannis, D. P., Cohen, A., Martin, T., Giralt, S., Champlin, R.
(2004). Tumor necrosis factor-{alpha} blockade for the treatment of acute GVHD. Blood
104: 649-654
[Abstract][Full Text]
Goedkoop, A Y, Kraan, M C, Teunissen, M B M, Picavet, D I, de Rie, M A, Bos, J D, Tak, P P
(2004). Early effects of tumour necrosis factor {alpha} blockade on skin and synovial tissue in patients with active psoriasis and psoriatic arthritis. Ann Rheum Dis
63: 769-773
[Abstract][Full Text]
Sandborn, W J, Loftus, E V
(2004). Balancing the risks and benefits of infliximab in the treatment of inflammatory bowel disease. Gut
53: 780-782
[Full Text]
Somasekar, A, Alcolado, R
(2004). Genital condylomata in a patient receiving infliximab for Crohn's disease. Postgrad. Med. J.
80: 358-359
[Abstract][Full Text]
Kyttaris, V C, Juang, Y-T, Tsokos, G C
(2004). Gene therapy in systemic lupus erythematosus. Lupus
13: 353-358
[Abstract]
Kirkegaard, T, Hansen, A, Bruun, E, Brynskov, J
(2004). Expression and localisation of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn's disease. Gut
53: 701-709
[Abstract][Full Text]
Nayar, M, Rhodes, J M
(2004). Management of inflammatory bowel disease. Postgrad. Med. J.
80: 206-213
[Abstract][Full Text]
Sands, B. E., Anderson, F. H., Bernstein, C. N., Chey, W. Y., Feagan, B. G., Fedorak, R. N., Kamm, M. A., Korzenik, J. R., Lashner, B. A., Onken, J. E., Rachmilewitz, D., Rutgeerts, P., Wild, G., Wolf, D. C., Marsters, P. A., Travers, S. B., Blank, M. A., van Deventer, S. J.
(2004). Infliximab Maintenance Therapy for Fistulizing Crohn's Disease. NEJM
350: 876-885
[Abstract][Full Text]
Fiocchi, C.
(2004). Closing Fistulas in Crohn's Disease -- Should the Accent Be on Maintenance or Safety?. NEJM
350: 934-936
[Full Text]
Greiner, K., Murphy, C. C., Willermain, F., Duncan, L., Plskova, J., Hale, G., Isaacs, J. D., Forrester, J. V., Dick, A. D.
(2004). Anti-TNF{alpha} Therapy Modulates the Phenotype of Peripheral Blood CD4+ T Cells in Patients with Posterior Segment Intraocular Inflammation. IOVS
45: 170-176
[Abstract][Full Text]
Di Sabatino, A, Ciccocioppo, R, Cinque, B, Millimaggi, D, Morera, R, Ricevuti, L, Cifone, M G, Corazza, G R
(2004). Defective mucosal T cell death is sustainably reverted by infliximab in a caspase dependent pathway in Crohn's disease. Gut
53: 70-77
[Abstract][Full Text]
Marty, F. M., Lee, S. J., Fahey, M. M., Alyea, E. P., Soiffer, R. J., Antin, J. H., Baden, L. R.
(2003). Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study. Blood
102: 2768-2776
[Abstract][Full Text]
Dan, N., Kanai, T., Totsuka, T., Iiyama, R., Yamazaki, M., Sawada, T., Miyata, T., Yagita, H., Okumura, K., Watanabe, M.
(2003). Ameliorating effect of anti-Fas ligand MAb on wasting disease in murine model of chronic colitis. Am. J. Physiol. Gastrointest. Liver Physiol.
285: G754-G760
[Abstract][Full Text]
Nahar, I. K, Shojania, K., Marra, C. A, Alamgir, A. H, Anis, A. H
(2003). Infliximab Treatment of Rheumatoid Arthritis and Crohn's Disease. The Annals of Pharmacotherapy
37: 1256-1265
[Abstract][Full Text]
Foell, D, Kucharzik, T, Kraft, M, Vogl, T, Sorg, C, Domschke, W, Roth, J
(2003). Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease. Gut
52: 847-853
[Abstract][Full Text]
Cope, A. P.
(2003). Exploring the reciprocal relationship between immunity and inflammation in chronic inflammatory arthritis. Rheumatology (Oxford)
42: 716-731
[Abstract][Full Text]
Hanauer, S. B., Rutgeerts, P., Baert, F., Noman, M.
(2003). Immunogenicity of Infliximab in Crohn's Disease. NEJM
348: 2155-2156
[Full Text]
Long, R., Gardam, M.
(2003). Tumour necrosis factor-{alpha} inhibitors and the reactivation of latent tuberculosis infection. CMAJ
168: 1153-1156
[Full Text]
Schwartz, R. S.
(2003). Diversity of the Immune Repertoire and Immunoregulation. NEJM
348: 1017-1026
[Full Text]
Gottlieb, A B
(2003). Clinical research helps elucidate the role of tumor necrosis factor-{alpha}in the pathogenesis of T1-mediated immune disorders: use of targeted immunotherapeutics as pathogenic probes. Lupus
12: 190-194
[Abstract]
Baert, F., Noman, M., Vermeire, S., Van Assche, G., D' Haens, G., Carbonez, A., Rutgeerts, P.
(2003). Influence of Immunogenicity on the Long-Term Efficacy of Infliximab in Crohn's Disease. NEJM
348: 601-608
[Abstract][Full Text]
Myers, K. J., Murthy, S., Flanigan, A., Witchell, D. R., Butler, M., Murray, S., Siwkowski, A., Goodfellow, D., Madsen, K., Baker, B.
(2003). Antisense Oligonucleotide Blockade of Tumor Necrosis Factor-alpha in Two Murine Models of Colitis. J. Pharmacol. Exp. Ther.
304: 411-424
[Abstract][Full Text]
Marzo-Ortega, H, McGonagle, D, O'Connor, P, Emery, P
(2003). Efficacy of etanercept for treatment of Crohn's related spondyloarthritis but not colitis. Ann Rheum Dis
62: 74-76
[Abstract][Full Text]
Sewell, K. L., Geary, R. S., Baker, B. F., Glover, J. M., Mant, T. G. K., Yu, R. Z., Tami, J. A., Dorr, F. A.
(2002). Phase I Trial of ISIS 104838, a 2'-Methoxyethyl Modified Antisense Oligonucleotide Targeting Tumor Necrosis Factor-alpha. J. Pharmacol. Exp. Ther.
303: 1334-1343
[Abstract][Full Text]
Hallegua, D S, Weisman, M H
(2002). Potential therapeutic uses of interleukin 1 receptor antagonists in human diseases. Ann Rheum Dis
61: 960-967
[Abstract][Full Text]
Burgos-Vargas, R
(2002). Juvenile onset spondyloarthropathies: therapeutic aspects. Ann Rheum Dis
61: iii33-39
[Abstract][Full Text]
Braun, J, Sieper, J, Breban, M, Collantes-Estevez, E, Davis, J, Inman, R, Marzo-Ortega, H, Mielants, H
(2002). Anti-tumour necrosis factor {alpha} therapy for ankylosing spondylitis: international experience. Ann Rheum Dis
61: iii51-60
[Abstract][Full Text]
Gutierrez, O., Pipaon, C., Inohara, N., Fontalba, A., Ogura, Y., Prosper, F., Nunez, G., Fernandez-Luna, J. L.
(2002). Induction of Nod2 in Myelomonocytic and Intestinal Epithelial Cells via Nuclear Factor-kappa B Activation. J. Biol. Chem.
277: 41701-41705
[Abstract][Full Text]
Bartolucci, P., Ramanoelina, J., Cohen, P., Mahr, A., Godmer, P., Le Hello, C., Guillevin, L.
(2002). Efficacy of the anti-TNF-{alpha} antibody infliximab against refractory systemic vasculitides: an open pilot study on 10 patients. Rheumatology (Oxford)
41: 1126-1132
[Abstract][Full Text]
van Deventer, S J H
(2002). Anti-tumour necrosis factor therapy in Crohn's disease: where are we now?. Gut
51: 362-363
[Full Text]
Podolsky, D. K.
(2002). Inflammatory Bowel Disease. NEJM
347: 417-429
[Full Text]
Brynskov, J, Foegh, P, Pedersen, G, Ellervik, C, Kirkegaard, T, Bingham, A, Saermark, T
(2002). Tumour necrosis factor {alpha} converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease. Gut
51: 37-43
[Abstract][Full Text]
Foster, D. C.
(2002). Vulvar Disease. Obstet Gynecol
100: 145-163
[Abstract][Full Text]
Kruithof, E, Van den Bosch, F, Baeten, D, Herssens, A, De Keyser, F, Mielants, H, Veys, E M
(2002). Repeated infusions of infliximab, a chimeric anti-TNF{alpha} monoclonal antibody, in patients with active spondyloarthropathy: one year follow up. Ann Rheum Dis
61: 207-212
[Abstract][Full Text]
Song, X.-y. R., Torphy, T. J., Griswold, D. E., Shealy, D.
(2002). Coming of Age:Anti-Cytokine Therapies. Mol. Interv.
2: 36-46
[Abstract][Full Text]
ten Hove, T, van Montfrans, C, Peppelenbosch, M P, van Deventer, S J H
(2002). Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease. Gut
50: 206-211
[Abstract][Full Text]
Drewe, E, Powell, R J
(2002). Clinically useful monoclonal antibodies in treatment. J. Clin. Pathol.
55: 81-85
[Abstract][Full Text]
Hendrickson, B. A., Gokhale, R., Cho, J. H.
(2002). Clinical Aspects and Pathophysiology of Inflammatory Bowel Disease. Clin. Microbiol. Rev.
15: 79-94
[Abstract][Full Text]
Voigtlander, C., Luftl, M., Schuler, G., Hertl, M.
(2001). Infliximab (Anti-Tumor Necrosis Factor {alpha} Antibody): A Novel, Highly Effective Treatment of Recalcitrant Subcorneal Pustular Dermatosis (Sneddon-Wilkinson Disease). Arch Dermatol
137: 1571-1574
[Full Text]
BOEGER, C A, WITTWER, H, SCHATTENKIRCHNER, M, KELLNER, H, KELLNER, W
(2001). Treatment of ankylosing spondylitis with infliximab. Ann Rheum Dis
60: 1159-1160
[Full Text]
Van den Bosch, F, Baeten, D, Kruithof, E, De Keyser, F, Mielants, H, Veys, E M
(2001). Treatment of active spondyloarthropathy with infliximab, the chimeric monoclonal antibody to tumour necrosis factor alpha. Ann Rheum Dis
60: iii33-36
[Full Text]
Tan, M.-H., Gordon, M., Lebwohl, O., George, J., Lebwohl, M. G.
(2001). Improvement of Pyoderma Gangrenosum and Psoriasis Associated With Crohn Disease With Anti-Tumor Necrosis Factor {alpha} Monoclonal Antibody. Arch Dermatol
137: 930-933
[Abstract][Full Text]
Barrera, P, Joosten, L A B, den Broeder, A A, van de Putte, L B A, van Riel, P L C M, van den Berg, W B
(2001). Effects of treatment with a fully human anti-tumour necrosis factor {alpha} monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNF{alpha} in patients with rheumatoid arthritis. Ann Rheum Dis
60: 660-669
[Abstract][Full Text]
Conroy, C A, Cattell, R
(2001). Infliximab treatment for Crohn's disease. Postgrad. Med. J.
77: 436-440
[Full Text]
Byrd, J. C., Murphy, T., Howard, R. S., Lucas, M. S., Goodrich, A., Park, K., Pearson, M., Waselenko, J. K., Ling, G., Grever, M. R., Grillo-Lopez, A. J., Rosenberg, J., Kunkel, L., Flinn, I. W.
(2001). Rituximab Using A Thrice Weekly Dosing Schedule in B-Cell Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma Demonstrates Clinical Activity and Acceptable Toxicity. JCO
19: 2153-2164
[Abstract][Full Text]
Warris, A., Bjorneklett, A., Gaustad, P., Keenan, G. F., Schaible, T. F., Boscia, J. A.
(2001). Invasive Pulmonary Aspergillosis Associated with Infliximab Therapy. NEJM
344: 1099-1100
[Full Text]
Onda, M., Willingham, M., Wang, Q.-c., Kreitman, R. J., Tsutsumi, Y., Nagata, S., Pastan, I.
(2000). Inhibition of TNF-{alpha} Produced by Kupffer Cells Protects Against the Nonspecific Liver Toxicity of Immunotoxin Anti-Tac(Fv)-PE38, LMB-2. J. Immunol.
165: 7150-7156
[Abstract][Full Text]
Klippel, J. H.
(2000). Biologic Therapy for Rheumatoid Arthritis. NEJM
343: 1640-1641
[Full Text]
Braun, J., Xiang, J., Brandt, J., Maetzel, H., Haibel, H., Wu, P., Kohler, S., Rudwaleit, M., Siegert, S., Radbruch, A., Thiel, A., Sieper, J.
(2000). Treatment of spondyloarthropathies with antibodies against tumour necrosis factor alpha : first clinical and laboratory experiences. Ann Rheum Dis
59: i85-89
[Full Text]
Stallmach, A, Chan, C C, Ecker, K-W, Feifel, G, Herbst, H, Schuppan, D, Zeitz, M
(2000). Comparable expression of matrix metalloproteinases 1 and 2 in pouchitis and ulcerative colitis. Gut
47: 415-422
[Abstract][Full Text]
Casson, D H, Eltumi, M, Tomlin, S, Walker-Smith, J A, Murch, S H
(2000). Topical tacrolimus may be effective in the treatment of oral and perineal Crohn's disease. Gut
47: 436-440
[Abstract][Full Text]
BRAUN, J, SIEPER, J
(2000). Anti-TNFalpha : a new dimension in the pharmacotherapy of the spondyloarthropathies !?. Ann Rheum Dis
59: 404-407
[Full Text]
Van den Bosch, F., Kruithof, E., Baeten, D., De Keyser, F., Mielants, H., Veys, E. M
(2000). Effects of a loading dose regimen of three infusions of chimeric monoclonal antibody to tumour necrosis factor alpha (infliximab) in spondyloarthropathy: an open pilot study. Ann Rheum Dis
59: 428-433
[Abstract][Full Text]
Geyer, A. S., Anhalt, G. J., Nousari, H. C.
(2000). Effectiveness of Infliximab in the Treatment of Refractory Perineal Cutaneous Crohn Disease. Arch Dermatol
136: 459-460
[Full Text]
Hartmann, G., Bidlingmaier, C., Siegmund, B., Albrich, S., Schulze, J., Tschoep, K., Eigler, A., Lehr, H. A., Endres, S.
(2000). Specific Type IV Phosphodiesterase Inhibitor Rolipram Mitigates Experimental Colitis in Mice. J. Pharmacol. Exp. Ther.
292: 22-30
[Abstract][Full Text]
Rampton, D. S
(1999). Regular review: Management of Crohn's disease. BMJ
319: 1480-1485
[Full Text]
(1999). Infliximab Promotes Healing of Fistulas in Crohn's Disease. JWatch General
1999: 5-5
[Full Text]
, has recently been developed as a treatment for Crohn's disease. We conducted a randomized, multicenter, double-blind, placebo-controlled trial of infliximab for the treatment of fistulas in patients with Crohn's disease. 
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