A randomized placebo-controlled trial of a humanized monoclonal antibody to α4 integrin in active crohn's disease

Gordon, F.; Lai, Clement; Hamilton, Mark; Allison, M. E. M.; Srivastava, E. D.; Fouweather, Marilyn G.; Donoghue, Stephen; Greenlees, Carol; Subhani, J; Amlot, Peter; Pounder, R. E.

doi:10.1053/gast.2001.26260

Cited by 312 publications

(146 citation statements)

References 18 publications

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“…13,14 Natalizumab (Antegren, Elan Pharmaceuticals and Biogen), a recombinant, humanized monoclonal antibody against a 4 integrin, improved the signs and symptoms of patients with Crohn's disease or ulcerative colitis in two pilot studies. 15,16 We conducted a large, randomized, placebo-controlled trial of this selective adhesion-molecule inhibitor in patients with moderate-to-severe Crohn's disease.…”

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confidence: 99%

Natalizumab for Active Crohn's Disease

et al. 2003

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Natalizumab for Active Crohn's Disease

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“…It is approved for treating both multiple sclerosis and Crohn's disease. This was the first therapeutic antibody to target leukocyte adhesion molecules to treat Crohn's disease [71][72][73]. Natalizumab is effective, but since it carries a small risk for reactivation of the John Cunningham (JC) polyoma virus, it has been restricted for use only [73].…”

Section: Currently Available Therapeutic Antibodies In Digestive Disementioning

confidence: 99%

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

Sofia

Rubin

2017

Dig Dis Sci

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The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

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“…The most successful was natalizumab, a humanized antibody directed against ␣ 4 integrin (CD49d) tested in MS, as well as Crohn's disease. [62][63][64] Natalizumab was approved by the United States Food and Drug Administration for the treatment of MS based on its ability to significantly reduce the relapse rate in patients with relapsing-remitting MS. However, progressive multifocal leucoencephalopathy (PML) developed in two patients receiving natalizumab in combination with interferon-beta-1a.…”

Section: Co-stimulatory Blockade In Eae: An Animal Model Of Msmentioning

confidence: 99%

Modulating Co-Stimulation

Viglietta

Khoury

2007

Neurotherapeutics

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Summary:The modulation of co-stimulatory pathways represents a novel therapeutic strategy to regulate autoimmune diseases. Auto-reactive CD4ϩ T cells play a critical role in initiating the immune response leading to inflammation and autoimmune diseases. Blocking co-stimulatory signals prevents T-cell activation, thus diminishing autoimmune responses and possibly preventing the progression of autoimmune disease. Blockade of several co-stimulatory pathways has been investigated in animal models and has led to clinical trials testing specific blocking agents in humans. In this review we will describe the role of co-stimulatory pathways, primarily the CD28-B7 pathway, in autoimmune diseases, and we will present in vivo and in vitro studies supporting the efficacy of co-stimulation blockade in animal models of autoimmune disease. Finally, we will discuss the clinical therapeutic efficacy of blocking monoclonal antibodies in preventing or reducing autoantigen driven T-cell activation in humans with particular attention to the CD28/B7 pathway. Inhibiting co-stimulatory molecule interactions by using monoclonal antibodies seems to be an original approach to regulate autoimmune diseases in humans.

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A randomized placebo-controlled trial of a humanized monoclonal antibody to α4 integrin in active crohn's disease

Cited by 312 publications

References 18 publications

Natalizumab for Active Crohn's Disease

Natalizumab for Active Crohn's Disease

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

Modulating Co-Stimulation

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