Mechanisms and Efficacy of Immunobiologic Therapies for Inflammatory Bowel Diseases

Current advances in understanding of the pathogenesis of inflammatory bowel disease have encouraged the development of many new therapies targeted at specific and non-specific mediators of the inflammatory bowel disease inflammatory pathway. Crohn's disease and ulcerative colitis, two common inflammatory bowel diseases likely result from interaction of multiple genetic and environmental risk and protective factors, deregulation of mucosal immunity in gut and breakdown of delicate balance of proinflammatory and anti-inflammatory cytokines. Immunobiologic agents targeted against TNF, leukocyte adhesion, Th1 polarization, T cell activation, nuclear factor-kappaB (NF-κB), and others are being assessed and will open exciting perspectives on development of therapies for inflammatory bowel disease.

[1]  S. Schreiber.  Certolizumab pegol for the treatment of Crohn’s disease , 2011, Therapeutic advances in gastroenterology.

[2]  J. Schölmerich,et al.  Emerging drugs to treat Crohn's disease , 2010, Expert opinion on emerging drugs.

[3]  P. Rutgeerts,et al.  A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease. , 2008, Gastroenterology.

[4]  Judy H. Cho,et al.  Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease , 2008, Nature Genetics.

[5]  Judy H. Cho,et al.  The genetics and immunopathogenesis of inflammatory bowel disease , 2008, Nature Reviews Immunology.

[6]  S. Hass,et al.  Health-Related Quality of Life During Natalizumab Maintenance Therapy for Crohn's Disease , 2007, The American Journal of Gastroenterology.

[7]  M. Regueiro,et al.  A phase I study of visilizumab, a humanized anti-CD3 monoclonal antibody, in severe steroid-refractory ulcerative colitis. , 2007, Gastroenterology.

[8]  S. Schreiber,et al.  Maintenance therapy with certolizumab pegol for Crohn's disease. , 2007, The New England journal of medicine.

[9]  S. Rutella,et al.  EDITOR’S QUIZ: GI SNAPSHOT , 2007, Gut.

[10]  S. Hanauer,et al.  Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial , 2007, Gut.

[11]  S. Hanauer,et al.  General principles and pharmacology of biologics in inflammatory bowel disease. , 2006, Gastroenterology clinics of North America.

[12]  S. Targan,et al.  Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial , 2006, Gut.

[13]  J. Schulzke,et al.  Randomized, Double Blind Controlled Trial of Subcutaneous Recombinant Human Interleukin-11 Versus Prednisolone in Active Crohn's Disease , 2006, The American Journal of Gastroenterology.

[14]  G. Radford-Smith,et al.  CDP571, a humanized monoclonal antibody to tumour necrosis factor‐α, for steroid‐dependent Crohn's disease: a randomized, double‐blind, placebo‐controlled trial , 2006, Alimentary pharmacology & therapeutics.

[15]  P. Rutgeerts,et al.  Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. , 2006, Gastroenterology.

[16]  Paul Rutgeerts,et al.  Infliximab for induction and maintenance therapy for ulcerative colitis. , 2005, The New England journal of medicine.

[17]  Yuji Naito,et al.  Role of matrix metalloproteinases in inflammatory bowel disease. , 2005, Molecular aspects of medicine.

[18]  C. Hawkey,et al.  Rdp58 Is a Novel and Potentially Effective Oral Therapy for Ulcerative Colitis , 2005, Inflammatory bowel diseases.

[19]  J. Korzenik,et al.  Sargramostim for active Crohn's disease. , 2005, The New England journal of medicine.

[20]  M. Neurath,et al.  Anti-interleukin-12 antibody for active Crohn's disease. , 2004, The New England journal of medicine.

[21]  J. Feisthammel,et al.  A randomised, controlled, double blind, escalating dose study of alicaforsen enema in active ulcerative colitis , 2004, Gut.

[22]  S. Hanauer,et al.  An Open-Label Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects with Prior Loss of Response or Intolerance to Infliximab for Crohn's Disease , 2004, American Journal of Gastroenterology.

[23]  W. Sandborn,et al.  Biologics in inflammatory bowel disease: how much progress have we made? , 2004, Gut.

[24]  S. Friedman.  General principles of medical therapy of inflammatory bowel disease. , 2004, Gastroenterology clinics of North America.

[25]  T. Hibi,et al.  A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease. , 2004, Gastroenterology.

[26]  P. Sarzi-Puttini,et al.  Infliximab-induced lupus in Crohn's disease: a case report. , 2003, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[27]  T. Yednock,et al.  Novel approaches to treating inflammatory bowel disease: targeting alpha-4 integrin , 2003, American Journal of Gastroenterology.

[28]  W. Sandborn,et al.  Mild to moderate Crohn's disease – defining the basis for a new treatment algorithm , 2003, Alimentary pharmacology & therapeutics.

[29]  R. Playford,et al.  Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis. , 2003, The New England journal of medicine.

[30]  I. S. Shaw,et al.  Basiliximab (anti‐CD25) in combination with steroids may be an effective new treatment for steroid‐resistant ulcerative colitis , 2003, Alimentary pharmacology & therapeutics.

[31]  G. Greenberg,et al.  Efficacy and safety of a humanized α4β7 antibody in active crohn's disease (CD) , 2003 .

[32]  P. Rutgeerts,et al.  A Pilot Study on the Use of the Humanized Anti–Interleukin-2 Receptor Antibody Daclizumab in Active Ulcerative Colitis , 2003, American Journal of Gastroenterology.

[33]  Subrata Ghosh,et al.  Natalizumab for active Crohn's disease. , 2003, The New England journal of medicine.

[34]  G. Porro,et al.  Inflammatory bowel disease: new insights into pathogenesis and treatment , 2002, Journal of internal medicine.

[35]  J. Korzenik,et al.  Treatment of active Crohn's disease with recombinant human granulocyte-macrophage colony-stimulating factor , 2002, The Lancet.

[36]  D. Coppola,et al.  RDP58, a locally active TNF inhibitor, is effective in the dextran sulphate mouse model of chronic colitis , 2002, Inflammation Research.

[37]  T. Kirkegaard,et al.  Tumour necrosis factor α converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease , 2002 .

[38]  S. Hanauer,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[39]  F. Dumont.  IDEC-131. IDEC/Eisai. , 2002, Current opinion in investigational drugs.

[40]  R. Pounder,et al.  A pilot study of treatment of active ulcerative colitis with natalizumab, a humanized monoclonal antibody to alpha‐4 integrin , 2002, Alimentary pharmacology & therapeutics.

[41]  B. Sands,et al.  Randomized, controlled trial of recombinant human interleukin‐11 in patients with active Crohn's disease , 2002, Alimentary pharmacology & therapeutics.

[42]  M. Grisham,et al.  Dysregulation of intestinal mucosal immunity: implications in inflammatory bowel disease. , 2001, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[43]  B. Beutler,et al.  Autoimmunity and Apoptosis: The Crohn's Connection , 2001 .

[44]  D. Jewell,et al.  Crohn's disease: genetic susceptibility, bacteria, and innate immunity , 2001, The Lancet.

[45]  Mourad Sahbatou,et al.  Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease , 2001, Nature.

[46]  Judy H. Cho,et al.  A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease , 2001, Nature.

[47]  T. Macdonald,et al.  IL-12 and Th1 immune responses in human Peyer's patches. , 2001, Trends in immunology.

[48]  S. Targan,et al.  An engineered human antibody to TNF (CDP571) for active Crohn's disease: a randomized double-blind placebo-controlled trial. , 2001, Gastroenterology.

[49]  L. Mortelmans,et al.  Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. , 2001, Gastroenterology.

[50]  M. Camilleri,et al.  Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects , 2001, Alimentary pharmacology & therapeutics.

[51]  Y. Mahida,et al.  NF‐κB may determine whether epithelial cell–microbial interactions in the intestine are hostile or friendly , 2001, Clinical and experimental immunology.

[52]  S. Targan,et al.  Tumor necrosis factor: biology and therapeutic inhibitors. , 2000, Gastroenterology.

[53]  D. Elliott,et al.  Does the failure to acquire helminthic parasites predispose to Crohn's disease? , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[54]  W. Fiers,et al.  Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. , 2000, Science.

[55]  P. Delves,et al.  The immune system. Second of two parts. , 2000, The New England journal of medicine.

[56]  D. Schuppan,et al.  MMPs in the gut: inflammation hits the matrix , 2000, Gut.

[57]  G. Kollias,et al.  Inhibition of Tumor Necrosis Factor mRNA Translation by a Rationally Designed Immunomodulatory Peptide* , 2000, The Journal of Biological Chemistry.

[58]  J. Korzenik,et al.  Is Crohn's Disease an Immunodeficiency? , 2000, Digestive Diseases and Sciences.

[59]  G. Greenberg,et al.  A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators. , 2000, The New England journal of medicine.

[60]  M. Mckinley,et al.  A preliminary study of growth hormone therapy for Crohn's disease. , 2000, The New England journal of medicine.

[61]  T. Kishimoto,et al.  IL-6 Is Required for the Development of Th1 Cell-Mediated Murine Colitis1 , 2000, The Journal of Immunology.

[62]  M. Neurath,et al.  Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: Evidence in Crohn disease and experimental colitis in vivo , 2000, Nature Medicine.

[63]  G. Greenberg,et al.  A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease , 2000 .

[64]  W. Petritsch,et al.  Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI. , 2000, Gastroenterology.

[65]  E. Vasiliauskas,et al.  Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease. , 1999, Gastroenterology.

[66]  A. Levine,et al.  References Subscriptions Permissions Email Alerts Resistance of Crohn's Disease T Cells to Multiple Apoptotic Signals Is Associated with a Bcl-2/Bax Mucosal Imbalance , 2013 .

[67]  A. Buchman,et al.  Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease. , 1999, Gastroenterology.

[68]  M. Neurath,et al.  T cell specificity and cross reactivity towards enterobacteria,Bacteroides,Bifidobacterium, and antigens from resident intestinal flora in humans , 1999, Gut.

[69]  R. Tersigni,et al.  Lamina propria T cells in Crohn's disease and other gastrointestinal inflammation show defective CD2 pathway-induced apoptosis. , 1999, Gastroenterology.

[70]  D. Podolsky,et al.  Growth factors in inflammatory bowel disease. , 1999, Inflammatory bowel diseases.

[71]  C. Fiocchi.  Inflammatory bowel disease: etiology and pathogenesis. , 1998, Gastroenterology.

[72]  Y. Matsuzawa,et al.  High Fas ligand expression on lymphocytes in lesions of ulcerative colitis , 1998, Gut.

[73]  C. Bennett,et al.  A placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn's disease. , 1998, Gastroenterology.

[74]  C. Moskaluk,et al.  IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells. , 1998, Journal of immunology.

[75]  M. Cottone,et al.  Mesalamine in the maintenance treatment of Crohn's disease: a meta-analysis adjusted for confounding variables. , 1997, Gastroenterology.

[76]  S. Targan,et al.  A Short-Term Study of Chimeric Monoclonal Antibody cA2 to Tumor Necrosis Factor α for Crohn's Disease , 1997 .

[77]  G. Kollias,et al.  A murine transmembrane tumor necrosis factor (TNF) transgene induces arthritis by cooperative p55/p75 TNF receptor signaling , 1997, European journal of immunology.

[78]  C. Elson,et al.  Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's disease. Crohn's Disease Study Group. , 1997, Gastroenterology.

[79]  C. FordAlexander,et al.  ULCERATIVE colitis. , 1997, Journal of the American Medical Association.

[80]  Nicole Nelson,et al.  A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells , 1997, Nature.

[81]  M. Lambert,et al.  Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-α , 1997, Nature.

[82]  R. Testi,et al.  Stimulated human lamina propria T cells manifest enhanced Fas-mediated apoptosis. , 1996, The Journal of clinical investigation.

[83]  A. Dorner,et al.  Recombinant human IL-11 attenuates the inflammatory response through down-regulation of proinflammatory cytokine release and nitric oxide production. , 1996, Journal of immunology.

[84]  C. Feyerabend,et al.  In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells , 1996, European journal of gastroenterology & hepatology.

[85]  M. Göke,et al.  1 Regulation of the mucosal epithelial barrier , 1996 .

[86]  J. Keith,et al.  Protection by recombinant human interleukin-11 against experimental TNB-induced colitis in rats , 1996, Digestive Diseases and Sciences.

[87]  M. Neurath,et al.  Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. , 1996, Journal of immunology.

[88]  W. McCaskill-Stevens,et al.  A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy. , 1996, Blood.

[89]  L. Picker,et al.  Lymphocyte Homing and Homeostasis , 1996, Science.

[90]  M. Neurath,et al.  Antibodies to interleukin 12 abrogate established experimental colitis in mice , 1995, The Journal of experimental medicine.

[91]  F. Powrie,et al.  T cells in inflammatory bowel disease: protective and pathogenic roles. , 1995, Immunity.

[92]  G. Fick,et al.  Azathioprine and 6-Mercaptopurine in Crohn Disease , 1995, Annals of Internal Medicine.

[93]  D. Hommes,et al.  Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). , 1995, Gastroenterology.

[94]  Loyd,et al.  Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. , 1995, The New England journal of medicine.

[95]  S. Hanauer,et al.  Medical therapy for inflammatory bowel disease. , 1994, Gastroenterology clinics of North America.

[96]  C. Bennett,et al.  Inhibition of endothelial cell adhesion molecule expression with antisense oligonucleotides. , 1994, Journal of immunology.

[97]  R. Sartor,et al.  Cytokines in intestinal inflammation: pathophysiological and clinical considerations. , 1994, Gastroenterology.

[98]  K. Rajewsky,et al.  Interleukin-10-deficient mice develop chronic enterocolitis , 1993, Cell.

[99]  Geraint T. Williams,et al.  Smoking, humoral immunity, and ulcerative colitis. , 1991, Gut.

[100]  S. Meltzer,et al.  6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity. , 1989, Annals of internal medicine.

[101]  E. Lindberg,et al.  Smoking and inflammatory bowel disease. A case control study. , 1988, Gut.

[102]  C. la Vecchia,et al.  Nonspecific inflammatory bowel disease and smoking. , 1987, American journal of epidemiology.

[103]  R. Heatley,et al.  Smoking and colonic mucus in ulcerative colitis. , 1986, British medical journal.

[104]  M. Murphy,et al.  Reversible alterations in immunoregulatory T cells in smoking. Analysis by monoclonal antibodies and flow cytometry. , 1982, Chest.

[105]  P. Rutgeerts,et al.  Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. , 2007, Gastroenterology.

[106]  S. Hanauer,et al.  The state of the art in the management of inflammatory bowel disease. , 2003, Reviews in gastroenterological disorders.

[107]  A place for TACE , 2002 .

[108]  J. Korzenik,et al.  Is Crohn's disease an immunodeficiency? A hypothesis suggesting possible early events in the pathogenesis of Crohn's disease. , 2000, Digestive diseases and sciences.

[109]  M. Eaman.  Immune system. , 2000, Nursing standard (Royal College of Nursing (Great Britain) : 1987).

[110]  S. Ardizzone,et al.  Inflammatory bowel disease approaching the 3rd millennium: pathogenesis and therapeutic implications? , 1999, European journal of gastroenterology & hepatology.

[111]  B. Castner,et al.  A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. , 1997, Nature.

[112]  M. Göke,et al.  Regulation of the mucosal epithelial barrier. , 1996, Bailliere's clinical gastroenterology.

[113]  R. Willén,et al.  Impairment of bacterial flora in human ulcerative colitis and experimental colitis in the rat. , 1993, Digestion.

[114]  H. L. MacKechnie.  The immunology of inflammatory bowel disease. , 1982, Henry Ford Hospital medical journal.

[115]  I. Leodolter.  [Crohn's disease]. , 1967, Wiener Zeitschrift fur innere Medizin und ihre Grenzgebiete.

[116]  G PLACITELLI,et al.  [Ulcerative colitis]. , 1958, La Riforma medica.