Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis

Elliott, Michael J.; Maini, R. N.; Feldmann, Marc; Kalden, Joachim R.; Antoni, Christian; Smolen, Josef S.; Leeb, Burkhard F.; Breedveld, Ferdinand C.; Macfarlane, J. D.; Bijl, Heico M.

doi:10.1016/s0140-6736(94)90628-9

Cited by 1,555 publications

(855 citation statements)

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“…A relatively easy to measure PD marker currently described for TNF-blocking therapy is serum C-reactive protein levels. 2 In addition, cytokine levels for interleukin-1RA and interleukin-6 are described to be downregulated early after TNF-blockade and the change in interleukin-6 levels is associated with C-reactive protein reduction. 12 However, most of the described PD markers are assessed by using mean levels of patient groups and therefore do not necessarily apply for each individual patient.…”

Section: Discussionmentioning

confidence: 99%

“…1 Accordingly, TNF antagonists have proven to be effective for the treatment of RA. 2,3 Blockade of TNF reduces the acute phase response and decreases both local and systemic levels of inflammatory mediators in patients with RA (reviewed in Tracey et al 4 ). However, the improvement varies between patients, and approximately 30% of RA patients fail to respond to this therapy.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacogenomics of infliximab treatment using peripheral blood cells of patients with rheumatoid arthritis

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacogenomics of infliximab treatment using peripheral blood cells of patients with rheumatoid arthritis

et al. 2010

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“…On entry to the trial, all patients met the American College of Rheumatology (formerly, the American Rheumatism Association) criteria for RA (23): active RA for 2 6 months, a history of failed treatment with at least 1 disease-modifying antirheumatic drug, and evidence of erosive disease on radiography of the hands and feet. Active disease was defined as the presence of 2 6 swollen joints plus at least 3 of the following 4 secondary criteria: duration of morning stiffness 245 minutes, 2 6 tender or painful joints, erythrocyte sedimentation rate (ESR) 228 mm/hour, and C-reactive protein (CRP) level 220 mg/liter (12). Due to incomplete sampling, specimens were available for only 68 of the 73 patients.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, recent studies have demonstrated that anti-TNFa treatment of rats with active arthritis markedly improved clinical scores and was paralleled by inhibition of leukocyte accumulation in the joints (10). We have also reported that blockade of TNFa activity in vivo in patients with active RA by intravenous administration of monoclonal anti-TNFa antibody resulted in marked amelioration of disease, with significant improvements observed in all clinical and laboratory parameters (11,12). Suppression of the cytokine cascade is likely to be a cause of part of the therapeutic benefit of anti-TNFa, since studies from our laboratory have shown that the secretion of IL-1 and granulocytemacrophage colony-stimulating factor (GM-CSF) (13,14), and more recently, IL-6 and IL-8 (15) by cultured RA synovial membrane mononuclear cells was markedly reduced by the addition of anti-TNFa antibodies.…”

mentioning

confidence: 91%

Deactivation of vascular endothelium by monoclonal anti–tumor necrosis factor α antibody in rheumatoid arthritis

Paleolog

Hunt

Elliott

et al. 1996

Arthritis & Rheumatism

227

118

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Objective. To assess whether monoclonal antibody to tumor necrosis factor a (TNFa) reduces endothelial activation in rheumatoid arthritis (RA).Methods. Levels of serum E-selectin, intercellular adhesion molecule 1 (ICAM-l), and vascular cell adhesion molecule 1 (VCAM-l), and circulating leukocytes (differential counts) were measured in RA patients before and up to 4 weeks after infusion of either placebo or chimeric anti-TNFa antibody cA2 (1 or 10 mg/kg).Results. Treatment with anti-TNFa decreased serum E-selectin and ICAM-1 levels, with the earliest detectable changes observed on days 1-3 after anti-TNFa infusion. No effect on VCAM-1 levels was detected. In parallel, there was a rapid and sustained increase in circulating lymphocytes. The extent of the decrease in serum E-selectin and ICAM-1 levels and the increase in lymphocyte counts was significantly higher (P I 0.05) in patients in whom a clinical benefit of anti-TNFa was observed (120% response, by Paulus criteria, at week 4) compared with that in patients who failed to respond to anti-TNFa at this time point.Conclusion. We propose that decreased serum levels of adhesion molecules may reflect diminished activation of endothelial cells in the synovial microvas-

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“…In autoimmunity, the anti-tumour necrosis factor (TNF) α mAb infliximab has had a similar impact. Approved first for Crohn's disease in 1998, it has since been approved for ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis [6], and ulcerative colitis. Like rituximab, it has gone on to be administered to millions of patients.…”

Section: Introductionmentioning

confidence: 99%

Antibody modulation: Limiting the efficacy of therapeutic antibodies

Vaughan

Cragg

Beers

2015

Pharmacological Research

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Monoclonal antibodies (mAb) have revolutionised the way in which we treat disease.From cancer to autoimmunity, antibody therapy has been responsible for some of the most impressive clinical responses observed in the last 2 decades. A key component of this success has been their generally low levels of toxicity, and unique mechanisms of action. These two facets have allowed them to a) be integrated rapidly into clinical practice in combination with conventional radio-and chemotherapies and b) to avoid the resistance mechanisms typically observed with classical small molecule drugs, such as upregulation of drug efflux transporters, dysregulation of apoptosis and mutations in key target enzymes/pathways.Although success with mAb therapies has been impressive, they are also subject to their own resistance mechanisms. In this perspective we discuss the various ways in which mAb therapeutics can be inhibited, concentrating mainly on the ways in which they can be removed from the target cell surface -a process called modulation. This can be achieved either in a cis-fashion on a single cell or in trans, precipitated by engagement with a second phagocytic cell. The evidence for each of these processes will be discussed, in addition to possible therapeutic strategies that might be employed to inhibit or reverse them.Abbreviations: Fc gamma receptor, FcR; monoclonal antibody, mAb

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Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis

Cited by 1,555 publications

References 19 publications

Pharmacogenomics of infliximab treatment using peripheral blood cells of patients with rheumatoid arthritis

Pharmacogenomics of infliximab treatment using peripheral blood cells of patients with rheumatoid arthritis

Deactivation of vascular endothelium by monoclonal anti–tumor necrosis factor α antibody in rheumatoid arthritis

Antibody modulation: Limiting the efficacy of therapeutic antibodies

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