A Short-Term Study of Chimeric Monoclonal Antibody cA2 to Tumor Necrosis Factor for Crohn's Disease
Stephan R. Targan, M.D., Stephen B. Hanauer, M.D., Sander J.H. van Deventer, M.D., Ph.D., Lloyd Mayer, M.D., Daniel H. Present, M.D., Tanja Braakman, M.D., Kimberly L. DeWoody, M.S., Thomas F. Schaible, Ph.D., Paul J. Rutgeerts, M.D., Ph.D., for The Crohn's Disease cA2 Study Group
Background Studies in animals and an open-label trial have suggesteda role for antibodies to tumor necrosis factor , specificallychimeric monoclonal antibody cA2, in the treatment of Crohn'sdisease.
Methods We conducted a 12-week multicenter, double-blind, placebo-controlledtrial of cA2 in 108 patients with moderate-to-severe Crohn'sdisease that was resistant to treatment. All had scores on theCrohn's Disease Activity Index between 220 and 400 (scores canrange from 0 to about 600, with higher scores indicating moresevere illness). Patients were randomly assigned to receivea single two-hour intravenous infusion of either placebo orcA2 in a dose of 5 mg per kilogram of body weight, 10 mg perkilogram, or 20 mg per kilogram. Clinical response, the primaryend point, was defined as a reduction of 70 or more points inthe score on the Crohn's Disease Activity Index at four weeksthat was not accompanied by a change in any concomitant medications.
Results At four weeks, 81 percent of the patients given 5 mgof cA2 per kilogram (22 of 27 patients), 50 percent of thosegiven 10 mg of cA2 per kilogram (14 of 28), and 64 percent ofthose given 20 mg of cA2 per kilogram (18 of 28) had had a clinicalresponse, as compared with 17 percent of patients in the placebogroup (4 of 24) (P<0.001 for the comparison of the cA2 groupas a whole with placebo). Thirty-three percent of the patientsgiven cA2 went into remission (defined as a score below 150on the Crohn's Disease Activity Index), as compared with 4 percentof the patients given placebo (P = 0.005). At 12 weeks, 41 percentof the cA2-treated patients (34 of 83) had had a clinical response,as compared with 12 percent of the patients in the placebo group(3 of 25) (P = 0.008). The rates of adverse effects were similarin the groups.
Conclusions A single infusion of cA2 was an effective short-termtreatment in many patients with moderate-to-severe, treatment-resistantCrohn's disease.
Source Information
From the Cedars–Sinai Medical Center, Los Angeles (S.R.T.); the University of Chicago, Chicago (S.B.H.); Academisch Medisch Centrum, Amsterdam (S.J.H.D.); Mt. Sinai Medical Center, New York (L.M., D.H.P.); Centocor, Inc., Malvern, Pa. (T.B., K.L.D., T.F.S.); and Academisch Ziekenhuis Gasthuisberg, Leuven, Belgium (P.J.R.).
Address reprint requests to Dr. Targan at Cedars–Sinai Medical Center, Division of Gastroenterology and Inflammatory Bowel Disease Center D4063, 8700 Beverly Blvd., Los Angeles, CA 90048.
Bergamaschi, G., Di Sabatino, A., Albertini, R., Ardizzone, S., Biancheri, P., Bonetti, E., Cassinotti, A., Cazzola, P., Markopoulos, K., Massari, A., Rosti, V., Porro, G. B., Corazza, G. R.
(2010). Prevalence and pathogenesis of anemia in inflammatory bowel disease. Influence of anti-tumor necrosis factor-{alpha} treatment. haematol
95: 199-205
[Abstract][Full Text]
Seow, C H, Newman, A, Irwin, S P, Steinhart, A H, Silverberg, M S, Greenberg, G R
(2010). Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut
59: 49-54
[Abstract][Full Text]
Sokol, H, Beaugerie, L
(2009). Inflammatory bowel disease and lymphoproliferative disorders: the dust is starting to settle. Gut
58: 1427-1436
[Abstract][Full Text]
Lionaki, S., Siamopoulos, K., Theodorou, I., Papadimitraki, E., Bertsias, G., Boumpas, D., Boletis, J.
(2009). Inhibition of tumour necrosis factor alpha in idiopathic membranous nephropathy: a pilot study. Nephrol Dial Transplant
24: 2144-2150
[Abstract][Full Text]
Cesaro, A., Abakar-Mahamat, A., Brest, P., Lassalle, S., Selva, E., Filippi, J., Hebuterne, X., Hugot, J.-P., Doglio, A., Galland, F., Naquet, P., Vouret-Craviari, V., Mograbi, B., Hofman, P. M.
(2009). Differential expression and regulation of ADAM17 and TIMP3 in acute inflamed intestinal epithelia. Am. J. Physiol. Gastrointest. Liver Physiol.
296: G1332-G1343
[Abstract][Full Text]
Namba, T., Tanaka, K.-I., Ito, Y., Ishihara, T., Hoshino, T., Gotoh, T., Endo, M., Sato, K., Mizushima, T.
(2009). Positive Role of CCAAT/Enhancer-Binding Protein Homologous Protein, a Transcription Factor Involved in the Endoplasmic Reticulum Stress Response in the Development of Colitis. Am. J. Pathol.
174: 1786-1798
[Abstract][Full Text]
Belmiro, C. L. R., Castelo-Branco, M. T. L., Melim, L. M. C., Schanaider, A., Elia, C., Madi, K., Pavao, M. S. G., de Souza, H. S. P.
(2009). Unfractionated Heparin and New Heparin Analogues from Ascidians (Chordate-Tunicate) Ameliorate Colitis in Rats. J. Biol. Chem.
284: 11267-11278
[Abstract][Full Text]
Scholmerich, J.
(2009). Balancing the risks and benefits of prolonged use of infliximab. Gut
58: 477-478
[Full Text]
Schnitzler, F, Fidder, H, Ferrante, M, Noman, M, Arijs, I, Van Assche, G, Hoffman, I, Van Steen, K, Vermeire, S, Rutgeerts, P
(2009). Long-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort. Gut
58: 492-500
[Abstract][Full Text]
Onizawa, M., Nagaishi, T., Kanai, T., Nagano, K.-i., Oshima, S., Nemoto, Y., Yoshioka, A., Totsuka, T., Okamoto, R., Nakamura, T., Sakamoto, N., Tsuchiya, K., Aoki, K., Ohya, K., Yagita, H., Watanabe, M.
(2009). Signaling pathway via TNF-{alpha}/NF-{kappa}B in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis. Am. J. Physiol. Gastrointest. Liver Physiol.
296: G850-G859
[Abstract][Full Text]
Ferrari-Lacraz, S., Ferrari, S.
(2009). Effects of RANKL Inhibition on Inflammation and Immunity. IBMS BoneKEy
6: 116-126
[Abstract][Full Text]
Ebert, E. C.
(2009). Infliximab and the TNF-{alpha} system. Am. J. Physiol. Gastrointest. Liver Physiol.
296: G612-G620
[Abstract][Full Text]
Winfield, R. D., Delano, M. J., Pande, K., Scumpia, P. O., LaFace, D., Moldawer, L. L.
(2008). Myeloid-Derived Suppressor Cells in Cancer Cachexia Syndrome: A New Explanation for an Old Problem. JPEN J Parenter Enteral Nutr
32: 651-655
[Abstract][Full Text]
Edelblum, K. L., Goettel, J. A., Koyama, T., McElroy, S. J., Yan, F., Polk, D. B.
(2008). TNFR1 Promotes Tumor Necrosis Factor-mediated Mouse Colon Epithelial Cell Survival through RAF Activation of NF-{kappa}B. J. Biol. Chem.
283: 29485-29494
[Abstract][Full Text]
Yan, Y., Dalmasso, G., Nguyen, H. T. T., Obertone, T. S., Charrier-Hisamuddin, L., Sitaraman, S. V., Merlin, D.
(2008). Nuclear Factor-{kappa}B Is a Critical Mediator of Ste20-Like Proline-/Alanine-Rich Kinase Regulation in Intestinal Inflammation. Am. J. Pathol.
173: 1013-1028
[Abstract][Full Text]
Blumberg, R. S.
(2008). Crohn Disease. JAMA
300: 439-440
[Full Text]
Wiese, D. M., Rivera, R., Seidner, D. L.
(2008). Is There a Role for Bowel Rest in Nutrition Management of Crohn's Disease?. Nutr Clin Pract
23: 309-317
[Abstract][Full Text]
Horino, J., Fujimoto, M., Terabe, F., Serada, S., Takahashi, T., Soma, Y., Tanaka, K., Chinen, T., Yoshimura, A., Nomura, S., Kawase, I., Hayashi, N., Kishimoto, T., Naka, T.
(2008). Suppressor of cytokine signaling-1 ameliorates dextran sulfate sodium-induced colitis in mice. Int Immunol
20: 753-762
[Abstract][Full Text]
Kronqvist, N., Lofblom, J., Jonsson, A., Wernerus, H., Stahl, S.
(2008). A novel affinity protein selection system based on staphylococcal cell surface display and flow cytometry. Protein Eng Des Sel
21: 247-255
[Abstract][Full Text]
Fries, W., Muja, C., Crisafulli, C., Cuzzocrea, S., Mazzon, E.
(2008). Dynamics of enterocyte tight junctions: effect of experimental colitis and two different anti-TNF strategies. Am. J. Physiol. Gastrointest. Liver Physiol.
294: G938-G947
[Abstract][Full Text]
Rowlett, R. M., Chrestensen, C. A., Nyce, M., Harp, M. G., Pelo, J. W., Cominelli, F., Ernst, P. B., Pizarro, T. T., Sturgill, T. W., Worthington, M. T.
(2008). MNK kinases regulate multiple TLR pathways and innate proinflammatory cytokines in macrophages. Am. J. Physiol. Gastrointest. Liver Physiol.
294: G452-G459
[Abstract][Full Text]
Forbes, A
(2007). Crohn's disease or abdominal tuberculosis?. Gut
56: 1757-1758
[Full Text]
Tran, C. N., Lundy, S. K., White, P. T., Endres, J. L., Motyl, C. D., Gupta, R., Wilke, C. M., Shelden, E. A., Chung, K. C., Urquhart, A. G., Fox, D. A.
(2007). Molecular Interactions between T Cells and Fibroblast-Like Synoviocytes: Role of Membrane Tumor Necrosis Factor-{alpha} on Cytokine-Activated T Cells. Am. J. Pathol.
171: 1588-1598
[Abstract][Full Text]
Treede, I., Braun, A., Sparla, R., Kuhnel, M., Giese, T., Turner, J. R., Anes, E., Kulaksiz, H., Fullekrug, J., Stremmel, W., Griffiths, G., Ehehalt, R.
(2007). Anti-inflammatory Effects of Phosphatidylcholine. J. Biol. Chem.
282: 27155-27164
[Abstract][Full Text]
Hanauer, S. B
(2007). Risks and benefits of combining immunosuppressives and biological agents in inflammatory bowel disease: is the synergy worth the risk?. Gut
56: 1181-1183
[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]
Tanaka, K.-I., Namba, T., Arai, Y., Fujimoto, M., Adachi, H., Sobue, G., Takeuchi, K., Nakai, A., Mizushima, T.
(2007). Genetic Evidence for a Protective Role for Heat Shock Factor 1 and Heat Shock Protein 70 against Colitis. J. Biol. Chem.
282: 23240-23252
[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]
Schreiber, S., Khaliq-Kareemi, M., Lawrance, I. C., Thomsen, O. O., Hanauer, S. B., McColm, J., Bloomfield, R., Sandborn, W. J., the PRECISE 2 Study Investigators,
(2007). Maintenance Therapy with Certolizumab Pegol for Crohn's Disease. NEJM
357: 239-250
[Abstract][Full Text]
Lewis, J. D.
(2007). Anti-TNF Antibodies for Crohn's Disease -- In Pursuit of the Perfect Clinical Trial. NEJM
357: 296-298
[Full Text]
Berndt, U., Bartsch, S., Philipsen, L., Danese, S., Wiedenmann, B., Dignass, A. U., Hammerle, M., Sturm, A.
(2007). Proteomic Analysis of the Inflamed Intestinal Mucosa Reveals Distinctive Immune Response Profiles in Crohn's Disease and Ulcerative Colitis. J. Immunol.
179: 295-304
[Abstract][Full Text]
Sandborn, W. J., Rutgeerts, P., Enns, R., Hanauer, S. B., Colombel, J.-F., Panaccione, R., D'Haens, G., Li, J., Rosenfeld, M. R., Kent, J. D., Pollack, P. F.
(2007). Adalimumab Induction Therapy for Crohn Disease Previously Treated with Infliximab: A Randomized Trial. ANN INTERN MED
146: 829-838
[Abstract][Full Text]
Cohavy, O., Targan, S. R.
(2007). CD56 Marks an Effector T Cell Subset in the Human Intestine. J. Immunol.
178: 5524-5532
[Abstract][Full Text]
Van den Brande, J. M H, Koehler, T. C, Zelinkova, Z., Bennink, R. J, te Velde, A. A, ten Cate, F. J W, van Deventer, S. J H, Peppelenbosch, M. P, Hommes, D. W
(2007). Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn's disease. Gut
56: 509-517
[Abstract][Full Text]
Kuek, A., Hazleman, B. L, Ostor, A. J K
(2007). Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgrad. Med. J.
83: 251-260
[Abstract][Full Text]
Boivin, M. A., Ye, D., Kennedy, J. C., Al-Sadi, R., Shepela, C., Ma, T. Y.
(2007). Mechanism of glucocorticoid regulation of the intestinal tight junction barrier. Am. J. Physiol. Gastrointest. Liver Physiol.
292: G590-G598
[Abstract][Full Text]
Salliot, C., Gossec, L., Ruyssen-Witrand, A., Luc, M., Duclos, M., Guignard, S., Dougados, M.
(2007). Infections during tumour necrosis factor-{alpha} blocker therapy for rheumatic diseases in daily practice: a systematic retrospective study of 709 patients. Rheumatology (Oxford)
46: 327-334
[Abstract][Full Text]
Chen, M. C., Mudge, C. S., Klumpp, D. J.
(2006). Urothelial lesion formation is mediated by TNFR1 during neurogenic cystitis. Am. J. Physiol. Renal Physiol.
291: F741-F749
[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]
Kirkcaldy, J., Lim, W. S., Jones, A., Pointon, K.
(2006). Stridor in crohn disease and the use of infliximab.. Chest
130: 579-581
[Abstract][Full Text]
Florie, J., Wasser, M. N. J. M., Arts-Cieslik, K., Akkerman, E. M., Siersema, P. D., Stoker, J.
(2006). Dynamic Contrast-Enhanced MRI of the Bowel Wall for Assessment of Disease Activity in Crohn's Disease.. Am. J. Roentgenol.
186: 1384-1392
[Abstract][Full Text]
Rivera-Nieves, J., Burcin, T. L., Olson, T. S., Morris, M. A., McDuffie, M., Cominelli, F., Ley, K.
(2006). Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis. JEM
203: 907-917
[Abstract][Full Text]
Glauben, R., Batra, A., Fedke, I., Zeitz, M., Lehr, H. A., Leoni, F., Mascagni, P., Fantuzzi, G., Dinarello, C. A., Siegmund, B.
(2006). Histone hyperacetylation is associated with amelioration of experimental colitis in mice.. J. Immunol.
176: 5015-5022
[Abstract][Full Text]
Ye, D., Ma, I., Ma, T. Y.
(2006). Molecular mechanism of tumor necrosis factor-{alpha} modulation of intestinal epithelial tight junction barrier. Am. J. Physiol. Gastrointest. Liver Physiol.
290: G496-G504
[Abstract][Full Text]
Travis, S P L, Stange, E F, Lemann, M, Oresland, T, Chowers, Y, Forbes, A, D'Haens, G, Kitis, G, Cortot, A, Prantera, C, Marteau, P, Colombel, J-F, Gionchetti, P, Bouhnik, Y, Tiret, E, Kroesen, J, Starlinger, M, Mortensen, N J, for the European Crohn's and Colitis Organisation,
(2006). European evidence based consensus on the diagnosis and management of Crohn's disease: current management. Gut
55: i16-i35
[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]
Nambiar, P. R., Kirchain, S. M., Courmier, K., Xu, S., Taylor, N. S., Theve, E. J., Patterson, M. M., Fox, J. G.
(2006). Progressive Proliferative and Dysplastic Typhlocolitis in Aging Syrian Hamsters Naturally Infected with Helicobacter spp.: A Spontaneous Model of Inflammatory Bowel Disease. Veterinary Pathology
43: 2-14
[Abstract][Full Text]
Bamias, G., Nyce, M. R., De La Rue, S. A., Cominelli, F.
(2005). New Concepts in the Pathophysiology of Inflammatory Bowel Disease. ANN INTERN MED
143: 895-904
[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]
Watanabe, T, Kitani, A, Strober, W
(2005). NOD2 regulation of Toll-like receptor responses and the pathogenesis of Crohn's disease. Gut
54: 1515-1518
[Full Text]
Wolf, A. M., Wolf, D., Rumpold, H., Ludwiczek, S., Enrich, B., Gastl, G., Weiss, G., Tilg, H.
(2005). The kinase inhibitor imatinib mesylate inhibits TNF-{alpha} production in vitro and prevents TNF-dependent acute hepatic inflammation. Proc. Natl. Acad. Sci. USA
102: 13622-13627
[Abstract][Full Text]
Sato, T, Nakai, T, Tamura, N, Okamoto, S, Matsuoka, K, Sakuraba, A, Fukushima, T, Uede, T, Hibi, T
(2005). Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response. Gut
54: 1254-1262
[Abstract][Full Text]
van der Vaart, H., Koeter, G. H., Postma, D. S., Kauffman, H. F., ten Hacken, N. H. T.
(2005). First Study of Infliximab Treatment in Patients with Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med.
172: 465-469
[Abstract][Full Text]
Tokuyama, H., Ueha, S., Kurachi, M., Matsushima, K., Moriyasu, F., Blumberg, R. S., Kakimi, K.
(2005). The simultaneous blockade of chemokine receptors CCR2, CCR5 and CXCR3 by a non-peptide chemokine receptor antagonist protects mice from dextran sodium sulfate-mediated colitis. Int Immunol
17: 1023-1034
[Abstract][Full Text]
Akobeng, A K
(2005). Evidence in practice. Arch. Dis. Child.
90: 849-852
[Abstract][Full Text]
Titelbaum, D. S., Degenhardt, A., Kinkel, R. P.
(2005). Anti-Tumor Necrosis Factor Alpha-Associated Multiple Sclerosis. Am. J. Neuroradiol.
26: 1548-1550
[Abstract][Full Text]
Vesga, L, Terdiman, J P, Mahadevan, U
(2005). Adalimumab use in pregnancy. Gut
54: 890-890
[Full Text]
Fischer, U., Schulze-Osthoff, K.
(2005). New Approaches and Therapeutics Targeting Apoptosis in Disease. Pharmacol. Rev.
57: 187-215
[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]
Fowler, E V, Eri, R, Hume, G, Johnstone, S, Pandeya, N, Lincoln, D, Templeton, D, Radford-Smith, G L
(2005). TNF{alpha} and IL10 SNPs act together to predict disease behaviour in Crohn's disease. J. Med. Genet.
42: 523-528
[Abstract][Full Text]
Hunter, M. M., Wang, A., Hirota, C. L., McKay, D. M.
(2005). Neutralizing Anti-IL-10 Antibody Blocks the Protective Effect of Tapeworm Infection in a Murine Model of Chemically Induced Colitis. J. Immunol.
174: 7368-7375
[Abstract][Full Text]
Netea, M. G., Ferwerda, G., de Jong, D. J., Jansen, T., Jacobs, L., Kramer, M., Naber, T. H. J., Drenth, J. P. H., Girardin{paragraph}, S. E., Jan Kullberg, B., Adema, G. J., Van der Meer, J. W. M.
(2005). Nucleotide-Binding Oligomerization Domain-2 Modulates Specific TLR Pathways for the Induction of Cytokine Release. J. Immunol.
174: 6518-6523
[Abstract][Full Text]
Sturm, A., Rilling, K., Baumgart, D. C., Gargas, K., Abou-Ghazale, T., Raupach, B., Eckert, J., Schumann, Ralf. R., Enders, C., Sonnenborn, U., Wiedenmann, B., Dignass, A. U.
(2005). Escherichia coli Nissle 1917 Distinctively Modulates T-Cell Cycling and Expansion via Toll-Like Receptor 2 Signaling. Infect. Immun.
73: 1452-1465
[Abstract][Full Text]
Ma, T. Y., Boivin, M. A., Ye, D., Pedram, A., Said, H. M.
(2005). Mechanism of TNF-{alpha} modulation of Caco-2 intestinal epithelial tight junction barrier: role of myosin light-chain kinase protein expression. Am. J. Physiol. Gastrointest. Liver Physiol.
288: G422-G430
[Abstract][Full Text]
Mpofu, S., Fatima, F., Moots, R. J.
(2005). Anti-TNF-{alpha} therapies: they are all the same (aren't they?). Rheumatology (Oxford)
44: 271-273
[Full Text]
Heinzelmann, M., Bosshart, H.
(2005). Heparin Binds to Lipopolysaccharide (LPS)-Binding Protein, Facilitates the Transfer of LPS to CD14, and Enhances LPS-Induced Activation of Peripheral Blood Monocytes. J. Immunol.
174: 2280-2287
[Abstract][Full Text]
Rivera-Nieves, J., Olson, T., Bamias, G., Bruce, A., Solga, M., Knight, R. F., Hoang, S., Cominelli, F., Ley, K.
(2005). L-Selectin, {alpha}4{beta}1, and {alpha}4{beta}7 Integrins Participate in CD4+ T Cell Recruitment to Chronically Inflamed Small Intestine. J. Immunol.
174: 2343-2352
[Abstract][Full Text]
Goulet, C. J., Moseley, R. H., Tonnerre, C., Sandhu, I. S., Saint, S.
(2005). The Unturned Stone. NEJM
352: 489-494
[Full Text]
Hofstaedter, F
(2005). Granuloma formation in the different phenotypes of Crohn's disease. Gut
54: 180-181
[Full Text]
Cosnes, J, Nion-Larmurier, I, Beaugerie, L, Afchain, P, Tiret, E, Gendre, J-P
(2005). Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery. Gut
54: 237-241
[Abstract][Full Text]
Cohavy, O., Zhou, J., Ware, C. F., Targan, S. R.
(2005). LIGHT Is Constitutively Expressed on T and NK Cells in the Human Gut and Can Be Induced by CD2-Mediated Signaling. J. Immunol.
174: 646-653
[Abstract][Full Text]
Soderholm, J D, Streutker, C, Yang, P-C, Paterson, C, Singh, P K, McKay, D M, Sherman, P M, Croitoru, K, Perdue, M H
(2004). Increased epithelial uptake of protein antigens in the ileum of Crohn's disease mediated by tumour necrosis factor {alpha}. Gut
53: 1817-1824
[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]
Wang, H.-C., Montufar-Solis, D., Teng, B.-B., Klein, J. R.
(2004). Maximum Immunobioactivity of Murine Small Intestinal Intraepithelial Lymphocytes Resides in a Subpopulation of CD43+ T Cells. J. Immunol.
173: 6294-6302
[Abstract][Full Text]
Peppelenbosch, M P, van Deventer, S J H
(2004). T cell apoptosis and inflammatory bowel disease. Gut
53: 1556-1558
[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]
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]
Sandborn, W J, Faubion, W A
(2004). Biologics in inflammatory bowel disease: how much progress have we made?. Gut
53: 1366-1373
[Full Text]
Weigmann, B., Nemetz, A., Becker, C., Schmidt, J., Strand, D., Lehr, H. A., Galle, P. R., Ho, I.-C., Neurath, M. F.
(2004). A Critical Regulatory Role of Leucin Zipper Transcription Factor c-Maf in Th1-Mediated Experimental Colitis. J. Immunol.
173: 3446-3455
[Abstract][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]
Cohavy, O., Zhou, J., Granger, S. W., Ware, C. F., Targan, S. R.
(2004). LIGHT Expression by Mucosal T Cells May Regulate IFN-{gamma} Expression in the Intestine. J. Immunol.
173: 251-258
[Abstract][Full Text]
Mease, P
(2004). TNF{alpha} therapy in psoriatic arthritis and psoriasis. Ann Rheum Dis
63: 755-758
[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]
Ljung, T, Karlen, P, Schmidt, D, Hellstrom, P M, Lapidus, A, Janczewska, I, Sjoqvist, U, Lofberg, R
(2004). Infliximab in inflammatory bowel disease: clinical outcome in a population based cohort from Stockholm County. Gut
53: 849-853
[Abstract][Full Text]
Murphy, C. C., Greiner, K., Plskova, J., Duncan, L., Frost, A., Isaacs, J. D., Rebello, P., Waldmann, H., Hale, G., Forrester, J. V., Dick, A. D.
(2004). Neutralizing Tumor Necrosis Factor Activity Leads to Remission in Patients With Refractory Noninfectious Posterior Uveitis. Arch Ophthalmol
122: 845-851
[Abstract][Full Text]
Stallmach, A, Marth, T, Weiss, B, Wittig, B M, Hombach, A, Schmidt, C, Neurath, M, Zeitz, M, Zeuzem, S, Abken, H
(2004). An interleukin 12 p40-IgG2b fusion protein abrogates T cell mediated inflammation: anti-inflammatory activity in Crohn's disease and experimental colitis in vivo. Gut
53: 339-345
[Abstract][Full Text]
Ma, T. Y., Iwamoto, G. K., Hoa, N. T., Akotia, V., Pedram, A., Boivin, M. A., Said, H. M.
(2004). TNF-{alpha}-induced increase in intestinal epithelial tight junction permeability requires NF-{kappa}B activation. Am. J. Physiol. Gastrointest. Liver Physiol.
286: G367-G376
[Abstract][Full Text]
Booth, A., Harper, L., Hammad, T., Bacon, P., Griffith, M., Levy, J., Savage, C., Pusey, C., Jayne, D.
(2004). Prospective Study of TNF{alpha} Blockade with Infliximab in Anti-Neutrophil Cytoplasmic Antibody-Associated Systemic Vasculitis. J. Am. Soc. Nephrol.
15: 717-721
[Abstract][Full Text]
Hosoe, N., Miura, S., Watanabe, C., Tsuzuki, Y., Hokari, R., Oyama, T., Fujiyama, Y., Nagata, H., Ishii, H.
(2004). Demonstration of functional role of TECK/CCL25 in T lymphocyte-endothelium interaction in inflamed and uninflamed intestinal mucosa. Am. J. Physiol. Gastrointest. Liver Physiol.
286: G458-G466
[Abstract][Full Text]
Bhattacharya, S., Ray, R. M., Johnson, L. R.
(2004). Prevention of TNF-{alpha}-induced apoptosis in polyamine-depleted IEC-6 cells is mediated through the activation of ERK1/2. Am. J. Physiol. Gastrointest. Liver Physiol.
286: G479-G490
[Abstract][Full Text]
Murphy, C C, Duncan, L, Forrester, J V, Dick, A D
(2004). Systemic CD4+ T cell phenotype and activation status in intermediate uveitis. Br J Ophthalmol
88: 412-416
[Abstract][Full Text]
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