Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2)

Dullemen, Hendrik M. van; Deventer, S. J. H. Van; Hommes, Daan W.; Bijl, Heico M.; Jansen, J.; Tytgat, G. N. J.; Woody, James N.

doi:10.1016/0016-5085(95)90277-5

Cited by 1,032 publications

(511 citation statements)

References 14 publications

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“…In an experimental model of sepsis, rhG-CSF improved survival in a dose-dependent manner, and similar results were obtained in an endotoxin-induced lethal model in rodents [8,9,20,21]. The reduced mortality in the latter model was related to a rhG-CSFinduced suppression of systemic release of tumour necrosis factor (TNF); inhibition of TNF-ameliorates chronic IBD [22]. It is conceivable that modulation of mucosal cytokine production is one of the mechanisms of the rhG-CSF-induced reduction in the release of proinflammatory eicosanoids in immune complex colitis.…”

Section: Mono-/lymphocytesmentioning

confidence: 53%

Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis

Hommes¹,

Meenan²,

Dijkhuizen

et al. 1996

Clinical and Experimental Immunology

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SUMMARYInflammatory bowel disease is associated with mucosal neutrophil recruitment and activatation, mediated in part by arachidonic acid metabolites. G-CSF attenuates the immune response to sepsis and ameliorates glycogen storage disease Ib-related colitis. These actions may be effected through the shedding of neutrophil adhesion molecules, or inhibition of proinflammatory mediator synthesis. Immune complex colitis was used to evaluate the effect of rhG-CSF on colonic mucosal inflammation, neutrophil recruitment and the generation of eicosanoids. Immune complex colitis was induced in White New Zealand rabbits. Animals were pretreated with rhG-CSF either 24 h before induction, or at induction, with dosages of 50 and 200 g/kg. rhG-CSF caused a time-and dose-dependent neutrophilia in all animals. Pretreatment with rhG-CSF resulted in increased tissue myeloperoxidase levels, despite a histologically similar mucosal polymorphonuclear cell infiltrate between treated and control colitis groups. Leukotriene B 4 (LTB 4 ) and thromboxane B 2 (TXB 2 ) dialysis fluid levels were lower in treated animals, in particular in the groups receiving two doses (LTB 4 : both P < 0 : 01; TXB 2 : both P < 0 : 01. Prostaglandin E 2 (PGE 2 ) levels in dialysis fluid of the rhG-CSF-treated animals showed no difference from controls. In this model of experimental colitis, high-dose therapy with G-CSF resulted in a marked decrease of proinflammatory mediators, but mucosal generation of the protective PGE 2 was preserved. These results suggest that prolonged high-dose therapy with G-CSF may have anti-inflammatory effects in colitis.

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Section: Mono-/lymphocytesmentioning

confidence: 53%

Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis

Hommes¹,

Meenan²,

Dijkhuizen

et al. 1996

Clinical and Experimental Immunology

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“…It seems likely that either repeat dosing or a higher initial dose would be needed to provide further maintenance of this bene®cial effect. Good results have also been reported with this antibody in a small placeboblinded study in Crohn's disease 12 and with another TNFa antibody in Crohn's disease 6 as well as in rheumatoid arthritis. In rheumatoid arthritis repeat dosing has been used successfully without any signi®-cant clinical problems related to antibody development or allergic reaction.…”

Section: Discussionmentioning

confidence: 80%

“…Ó 1997 Blackwell Science Ltd remission was obtained in 8 out of 10 patients following a single dose of a TNFa antibody. 6 Murine monoclonal antibodies to cytokines have shown therapeutic effects in in¯ammatory disease but their use in humans is, as with other murine antibodies, limited by a short half-life (1±2 days) and the development of anti-mouse antibodies. To overcome these de®ciencies a genetically engineered anti-TNFa antibody has been constructed from human IgGc4 heavy chains and j light chains, which demonstrate a relatively reduced immunogenicity, and the complementarity determining regions (CDR) of a mouse TNFa antibody.…”

Section: Introductionmentioning

confidence: 99%

Treatment of ulcerative colitis with an engineered human anti‐TNFα antibody CDP571

Evans

Clarke

Heath

et al. 1997

Aliment Pharmacol Ther

130

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Background:Tumour Necrosis Factor‐alpha (TNFα) is a pro‐inflammatory cytokine whose expression is increased in the colonic mucosa of patients with active ulcerative colitis. TNFα antibodies have been shown to be beneficial in animal models of bowel inflammation and in Crohn's disease but have not previously been studied in ulcerative colitis.Methods:Patients with mild/moderate ulcerative colitis were treated openly with a single intravenous infusion of 5 mg/kg of an engineered human IgGγ4 antibody CDP571 and monitored for 8 weeks.Results:Fifteen patients entered the study, eight males and seven females, with a mean age of 44 years. Eleven had left‐sided disease, four extensive disease and six patients were steroid‐unresponsive. The treatment was well tolerated and plasma half‐life of CDP571 was ≈7 days. There was a significant reduction from 6.7 to 4.6 (P = 0.023) in the mean Powell–Tuck score by 1 week post‐infusion and a reduction to 5.5 was seen at 2 weeks (P = 0.218). Significant but modest reductions also occurred in erythrocyte sedimentation rate and serum C reactive protein in the first 2 weeks. Mean Interleukin‐6 plasma concentrations fell from 6.9 to 5.4 pg/mL by week 1, and to 6.1 pg/mL by week 2 (NS). Reductions in sigmoidoscopic score and number of liquid stools were noted but failed to reach statistical significance.Conclusion:A consistent improvement in disease activity was seen in the initial 2 weeks after infusion and the treatment was well tolerated. These promising results support the testing of CDP571 in a larger controlled trial.

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“…After case reports of successful use in patients with severe CD, an open-label study of INF in 10 steroid-resistant patients showed a marked decrease in CD activity index (CDAI) at week 8 [46]. This triggered the first multicenter, prospective, double-blind, placebo-controlled trial, which gave INF as a single dose of 5, 10, or 20 mg/kg and then followed the patientsclinical response for 12 weeks [47].…”

Section: Infmentioning

confidence: 99%

TNFα blockade in human diseases: An overview of efficacy and safety

Lin

Ziring

Desai

et al. 2008

Clinical Immunology

233

188

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Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2)

Cited by 1,032 publications

References 14 publications

Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis

Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis

Treatment of ulcerative colitis with an engineered human anti‐TNFα antibody CDP571

TNFα blockade in human diseases: An overview of efficacy and safety

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