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Andreakos E.T., Foxwell B.M., Brennan F.M., Maini R.N., Feldmann M. Cytokines and anti-cytokine biologicals in autoimmunity: present and future. Cytokine Growth Factor Rev. 13:2002;299-313.
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0035056003
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This article reviews in detail the development of anti-TNF therapy in rheumatoid arthritis. It discusses how early observations placing TNFα at the apex of a pro-inflammatory cascade operating in rheumatoid synovium were reproduced in the clinic in patients, and how anti-TNFα trials have provided insight into the pathophysiology of rheumatoid arthritis.
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Feldmann M., Maini R.N. Anti-TNF α therapy of rheumatoid arthritis: what have we learned? Annu Rev Immunol. 19:2001;163-196. This article reviews in detail the development of anti-TNF therapy in rheumatoid arthritis. It discusses how early observations placing TNFα at the apex of a pro-inflammatory cascade operating in rheumatoid synovium were reproduced in the clinic in patients, and how anti-TNFα trials have provided insight into the pathophysiology of rheumatoid arthritis.
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A historical review of the development of anti-TNFα therapy for rheumatoid arthritis, from the early in vitro and in vivo animal models observations to the initiation of the clinical trials and the licensing of anti-TNFα mAbs.
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Feldmann M. Development of anti-TNF therapy for rheumatoid arthritis. Nat Rev Immunol. 2:2002;364-371. A historical review of the development of anti-TNFα therapy for rheumatoid arthritis, from the early in vitro and in vivo animal models observations to the initiation of the clinical trials and the licensing of anti-TNFα mAbs.
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Elliott M.J., Maini R.N., Feldmann M., Long-Fox A., Charles P., Katsikis P., Brennan F.M., Walker J., Bijl H., Ghrayeb J., et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor α Arthritis Rheum. 36:1993;1681-1690.
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Elliott M.J., Maini R.N., Feldmann M., Kalden J.R., Antoni C., Smolen J.S., Leeb B., Breedveld F.C., Macfarlane J.D., Bijl H., et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis. Lancet. 344:1994;1105-1110.
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Rankin E.C., Choy E.H., Kassimos D., Kingsley G.H., Sopwith A.M., Isenberg D.A., Panayi G.S. The therapeutic effects of an engineered human anti-tumour necrosis factor alpha antibody (CDP571) in rheumatoid arthritis. Br J Rheumatol. 34:1995;334-342.
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Sander O., Rau R., van Riel P., van de Putte L., Hasler F., Baudin M., Ludin E., McAuliffe T., Dickinson S., Kahny M.-R., et al. Neutralization of TNF by Lenercept (TNFR55-IgG1, Ro 45-2081) in patients with rheumatoid arthritis treated for three months: results of a European phase II trial. Arthritis Rheum. 39:1996;S242.
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Weinblatt M.E., Kremer J.M., Bankhurst A.D., Bulpitt K.J., Fleischmann R.M., Fox R.I., Jackson C.G., Lange M., Burge D.J. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. New Engl J Med. 340:1999;253-259.
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Barrera P., Joosten L.A., den Broeder A.A., van de Putte L.B., van Riel P.L., van den Berg W.B. Effects of treatment with a fully human anti-tumour necrosis factor alpha monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNFalpha in patients with rheumatoid arthritis. Ann Rheum Dis. 60:2001;660-669.
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den Broeder A.A., Joosten L.A., Saxne T., Heinegard D., Fenner H., Miltenburg A.M., Frasa W.L., van Tits L.J., Buurman W.A., van Riel P.L., et al. Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation. Ann Rheum Dis. 61:2002;311-318. The effect of adalimumab (D2E7), a fully human anti-TNFα monoclonal antibody, on the radiological course in rheumatoid arthritis (RA) was studied. In parallel, the prognostic value of markers of cartilage turnover and endothelial activation in the course of bone damage was examined. It was found that a total of 15/36 (42%) patients presented no radiological progression after two years. More patients with stable radiological course were still receiving anti-TNFα treatment after two years (13/15 [87%] versus 11/21 [52%]; p = 0.03) and had lower baseline COMP (cartilage oligomeric matrix protein) and soluble ICAM-1 (sICAM-1) levels (p = 0.01 and 0.04, respectively) than those in the group with progressive disease. In a logistic regression model the combination of sustained TNF neutralization and baseline COMP and sICAM-1 levels could be predictive of radiological outcome (p = 0.03). These results suggest that long term monotherapy with adalimumab has a positive effect on the radiological outcome and modulates cartilage and synovium turnover as measured by biological markers. Baseline serum sICAM-1 levels and COMP levels could be useful in identifying patients with progressive or non-progressive radiological outcome.
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All reports of tuberculosis after infliximab therapy received (up to May 2001) through the MedWatch spontaneous reporting system of the Food and Drug Administration were analyzed. There were 70 reported cases of tuberculosis after treatment with infliximab, for a median of 12 weeks. This reported frequency of tuberculosis in association with infliximab therapy was much higher than the reported frequency of other opportunistic infections associated with this drug. In addition, the rate of reported cases of tuberculosis among patients treated with infliximab was higher than the available background rates. This study indicates that active tuberculosis can develop soon after the initiation of treatment with infliximab. Thus, physicians should screen patients for latent tuberculosis infection or disease before prescribing infliximab.
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Jiang Y., Genant H.K., Watt I., Cobby M., Bresnihan B., Aitchison R., McCabe D. A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum. 43:2000;1001-1009.
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Cohen S., Hurd E., Cush J., Schiff M., Weinblatt M.E., Moreland L.W., Kremer J., Bear M.B., Rich W.J., McCabe D. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 46:2002;614-624. The efficacy and safety of anakinra (a non-antibody antagonist of IL-1) in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) was evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. Patients with moderate-to-severe active RA who were receiving MTX for six consecutive months, with stable doses for greater than or equal to three months (those with disease duration of >six months but <12 years) were randomized into six groups: placebo or 0.04, 0.1, 0.4, 1.0 or 2.0 mg/kg of anakinra administered in a single, daily, subcutaneous injection. At week 12, the ACR20 (American College of Rheumatology) responses in the five active treatment plus MTX groups demonstrated a statistically significant (P = 0.001) dose-response relationship compared with the ACR20 response in the placebo plus MTX group. The ACR20 response rate in the anakinra 1.0 mg/kg (46%) and 2.0 mg/kg (38%) dose groups was significantly greater than that in the placebo group (19%). The ACR20 responses at 24 weeks were consistent with those at 12 weeks. These results suggest that in active RA patients, the combination of anakinra and MTX is safe and well tolerated and provides significantly greater clinical benefit than MTX alone.
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In an open label study, the efficacy of etanercept (Enbrel) in the treatment of steroid-dependent chronic graft-versus-host (GvHD) disease was investigated. Etanercept was given as a subcutaneous injection twice weekly for four weeks followed by once weekly for four more weeks, and progression or regression of chronic GvHD was monitored. At the end of the eight week treatment course, 80% of the patients had no adverse side effects, and 70% of them showed improvement. These results indicate that TNFα plays an important role in the pathophysiology of chronic GvHD and that etanercept may be beneficial for its treatment. Additional studies should be performed to optimize etanercept as a potential complementary therapy for resolution of steroid-dependent chronic GvHD.
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