Information de reference pour ce titreAccession Number: | 00005531-199410220-00007.
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Author: | Elliott, Michael J; Maini, Ravinder N; Feldmann, Marc; Kalden, Joachim R; Antoni, Christian; Smolen, Josef S; Leeb, Burkhard; Breedveld, Ferdinand C; Macfarlane, John D; Bijl, Hanny; Woody, James N.
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Institution: | Kennedy Institute of Rheumatology, Hammersmith, London W6 7DW, and Academic Department of Rheumatology, Charing Cross and Westminster Medical School, London, UK (M J Elliott PhD; Prof R N Maini FRCP; Prof M Feldmann PhD); Department of Internal Medicine III, Institute of Clinical Immunology and Rheumatology, Erlangen, Germany (Prof J R Kalden MD; C Antoni MD); Second Department of Medicine Rheumatic Diseases Centre, Lainz Hospital, and Ludwig Boltzmann Institute for Rheumatology, Vienna, Austria (Prof J S Smolen MD; B Leeb MD); Department of Rheumatology, University Hospital, Leiden, Netherlands (Prof F C Breedveld MD; J D Macfarlane MD); Centocor Inc, Malvern, Pennsylvania, USA (J A Bijl MD; J N Woody MD) Correspondence: Prof Ravinder N Maini.
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Title: | Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis.[Article]
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Source: | Lancet. 344(8930):1105-1110, October 22, 1994.
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Abstract: | SUMMARY: Tumour necrosis factor alpha (TNFalpha) is a critical inflammatory mediator in rheumatoid arthritis, and may therefore be a useful target for specific immunotherapy.In support of this hypothesis, we previously observed beneficial responses in patients with active rheumatoid arthritis after open-label administration of a chimeric monoclonal antibody to TNFalpha (cA2).
We now report the results of a four-centre, randomised double-blind trial of a single infusion of 1 or 10 mg/kg cA2 compared with placebo in 73 patients with active rheumatoid arthritis. The primary endpoint of the study was the achievement at week 4 of a Paulus 20% response, an amalgam of six clinical, observational, and laboratory variables. Intention-to-treat analysis of data from individual patients showed only 2 of 24 placebo recipients responding at this time, compared with 11 of 25 patients treated with low-dose cA2 (p=0.0083) and 19 of 24 patients treated with high-dose cA2 (p<0.0001). Over half of the high-dose cA2 patients responded by the more stringent 50% Paulus criteria at this time (p=0.0005). The magnitude of these responses was impressive, with maximum mean improvements in individual disease-activity assessments, such as tender or swollen-joint counts and in serum C-reactive protein, exceeding 60% for patients on high-dose treatment. There were two severe adverse events. 1 patient on 1 mg/kg cA2 developed pneumonia ("possibly" treatment-related) and 1 on 10 mg/kg had a fracture ("probably not" treatment-related).
The results provide the first good evidence that specific cytokine blockade can be effective in human inflammatory disease and define a new direction for the treatment of rheumatoid arthritis.
Copyright. (C) The Lancet Ltd, 1994.
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References: | 1. Brooks PM. Clinical managment of rheumatoid arthritis. Lancet 1993; 341: 286-90.
2. Brennan FM, Chantry D, Jackson A, Maini RN, Feldmann M. Inhibitory effect of TNFalpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 1989; ii: 244-47.
3. Haworth C, Brennan FM, Chantry D, et al. Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumour necrosis factor alpha. Eur J Immunol 1991; 21: 2575-79.
4. Williams RO, Feldmann M, Maini RN. Anti-tumour necrosis factor ameloriates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci USA 1992; 89: 9784-88.
5. Thorbecke GJ, Shah R, Leu CH, et al. Involvement of endogenous tumour necrosis factor alpha and transforming growth factor beta during induction of collagen type II arthritis in mice. Proc Natl Acad Sci USA 1992; 89: 7375-79.
6. Feldmann M, Brennan FM, Chu CQ, et al. Does TNFalpha have a pivotal role in the cytokine network in rheumatoid arthritis? In: Fiers W, ed. Tumor necrosis factor: molecular and cellular biology and clinical relevance. Basel: Karger, 1993: 144-52.
7. Maini RN, Brennan FM, Williams R, et al. TNFalpha in rheumatoid arthritis and prospects of anti-TNF therapy. Clin Exp Rheumatol 1993; 11 (suppl 8): S173-75.
8. Elliott MJ, Maini RN, Feldmann M, et al. Treatment of rheumatoid arthritis with chimaeric monoclonal antibodies to tumour necrosis factor alpha. Arthritis Rheum 1993; 36: 1681-90.
9. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315-24.
10. Steinbrocker O, Traeger CH, Batterman RC. Therapeutic criteria in rheumatoid arthritis. JAMA 1949; 140: 659-62.
11. Knight DM, Trinh H, Le J, et al. Construction and initial characterisation of a mouse-human chimaeric anti-TNF antibody. Mol Immunol 1993; 30: 1443-53.
12. Paulus HE, Egger MJ, Ward JR, et al. Analysis of improvement in individual rheumatoid arthritis patients treated with disease-modifying antirheumatic drugs, based on the findings in patients treated with placebo. Arthritis Rheum 1990; 33: 477-84.
13. Felson DT, Anderson JJ, Boers M, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum 1993; 36: 729-40.
14. Smolen J. EULAR standing committee for international clinical studies including therapeutic trials (ESCISIT). Rheumatol Eur 1994; 23: 37-39.
15. Elliott MJ, Maini RN, Feldmann M, et al. Repeated therapy with monoclonal antibody to tumour necrosis factor alpha (cA2) in patients with rheumatoid arthritis. Lancet 1994; 344: 1125-27.
16. Sewell KL, Parker KC, Woodworth TG, et al. DAB486IL-2 fusion toxin in refractory rheumatoid arthritis. Arthritis Rheum 1993; 36: 1223-33.
17. Moreland LW, Sewell KL, Sullivan WF, et al. Double blind placebo-controlled phase II trial of diphtheria-interleukin-2 fusion toxin (DAB486IL-2) in patients with refractory rheumatoid arthritis (RA). Arthritis Rheum 1993; 36: S39.
18. Elliott MJ, Maini RN. New directions for biological therapy in rheumatoid arthritis. Int Arch Allergy Appl Immunol 1994; 104: 112-25.
19. Moreland L, Pratt P, Mayes M, et al. Minimal efficacy of a depleting chimaeric anti-CD4 (cM-T412) in treatment of patients with refractory rheumatoid arthritis (RA) receiving concomitant methotrexate (MTX). Arthritis Rheum 1993; 36: S39.
20. Van der Lubbe PA, Dijkmans BA, Markusse HM, et al. Lack of clinical effect of CD4 monoclonal antibody therapy in early rheumatoid arthritis: a placebo controlled trial. Arthritis Rheum (in press).
21. Havell EA. Evidence that tumour necrosis factor has an important role in antibacterial resistance. J Immunol 1989; 143: 2894-99.
22. Pfeffer K, Matsuyama T, Kundig TM, et al. Mice deficient for the 55kd tumour necrosis factor receptor are resistant to endotoxic shock, yet succumb to L monocytogenes infection. Cell 1993; 73: 457-67.
23. Cope AP, Londei M, Chu NR, et al. Chronic exposure to TNFalpha in vitro impairs the activation of T cells through the T cell receptor/CD3 complex: reversal in vivo by anti-TNFalpha antibody in patients with rheumatoid arthritis. J Clin Invest 1994; 94: 749-60.
24. Roodman GD. Mechanisms of erythroid suppression in the anemia of chronic disease. Blood Cells 1987; 18: 171-84.
25. Johnson RA, Waddelow TA, Caro J, Oliff A, Roodman GD. Chronic exposure to tumour necrosis factor in vivo preferentially inhibits erythropoiesis in nude mice. Blood 1989; 74: 130-38.
26. Derkx B, Taminiau J, Radema S, et al. Tumour-necrosis-factor antibody treatment in Crohn's disease. Lancet 1993; 342: 173-74.
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Language: | English.
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Document Type: | Articles.
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Journal Subset: | Clinical Medicine.
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ISSN: | 0140-6736
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NLM Journal Code: | 2985213r, l0s, 0053266
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Annotation(s) | |
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