Abstract
Tumour necrosis factor (TNF)-α has been found to play a central role in the pathogenesis of rheumatoid arthritis, leading to development of novel drug therapies that neutralise the deleterious effects of this cytokine. This new concept of immunobiological treatment of rheumatoid arthritis has yielded successful results. Although the 2 currently available TNFα blockers, infliximab and etanercept, differ in structure, mechanism of action and pharmacokinetics, they have provided similar benefits both in clinical improvement and in slowing and even arresting the progression of radiographic damage. This therapeutic response seems to be unequalled by ‘conventional’ treatments in rheumatoid arthritis, and is incontestably a turning point in the therapeutic management of this disease.
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References
Brennan FM, Chantry D, Jackson A, et al. Inhibitory effect of TNFa antibodies on synovial cell IL-1 production in rheumatoid arthritis. Lancet 1989; ii: 244–7
Dinarello CA, Cannon JG, Wolff SM, et al. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med 1986; 163(6): 1433–50
Wallach D, Varfolomeev EE, Malinin NL, et al. Tumor necrosis factor receptor and Fas signaling mechanisms. Annu Rev Immunol 1999; 17: 331–67
May MJ, Gosh S. Signal transduction through NF-κB. Immunol Today 1998; 19: 80–8
Ulfgren AK, Andersson U, Engstrom M, et al. Systemic anti-tumor necrosis factor alfa therapy in rheumatoid arthritis downregulates synovial tumor necrosis factor alfa synthesis. Arthritis Rheum 2000; 43(11): 2391–6
Scallon BJ, Moore MA, Trinh H, et al. Chimeric anti-TNFα monoclonal antibody cA2 binds recombinant transmembrane TNFα and activates immune effector functions. Cytokines 1995; 7: 251–9
Williams RO, Feldman M, Maini RM. Anti-TNF ameliorates joint disease in murine collagen induced arthritis. Proc Natl Acad Sci U S A 1992; 89: 9784–8
Wooley PH, Dutcher J, Widmer MB, et al. Influence of a recombinant human soluble TNF receptor Fc fusion protein on type II collagen induced arthritis in mice. J Immunol 1993; 151: 6602–7
Maini R, St Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumor necrosis factor a monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Lancet 1999; 354: 1932–9
Lipsky PE, van der Heijde D, St Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med 2000; 343: 1594–602
Van der Heijde D. Joint erosions and patients with early rheumatoid arthritis. Br J Rheumatol 1995; 34Suppl. 2: 1216
Jeurissen ME, Boerbooms AM, van de Putte LBA, et al. Influence of methotrexate and azathioprine on radiologic progression in rheumatoid arthritis. A randomized, double-blind study. Ann Intern Med 1991; 114: 999–1004
Moreland LW, Baumgartner SW, Schiff MH, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997; 337: 141–7
Moreland LW, Schiff MH, Baumgartner SW, et al. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med 1999; 131: 478–86
Weinblatt ME, Kremer JM, Bankhurst AD, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor/Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999; 340: 253–9
Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000; 343: 1586–93
Infliximab (Remicade®): prescribing information. Malvern (PA): Centocor, 1999.
Etanercept (Enbrel®): prescribing information. Seattle (WA): Immunex Corporation, 2001. Available from: www.immunex.com/medinfo/pdf/enbpi.pdf [accessed 2001 Mar 27]
Stack WA, Mann SD, Roy AJ, et al. Randomized controlled trial of CDP571 antibody to tumour necrosis factor-α in Crohn’s disease. Lancet 1997; 349: 521–4
Bell S, Kamm MA. Antibodies to tumour necrosis factor alpha as treatment for Crohn’s disease. Lancet 2000; 355: 858–60
Rankin EC, Choy EH, Kassimos D, et al. The therapeutic effects of an engineered human anti-tumour necrosis factor α antibody (CDP571) in rheumatoid arthritis. Br JRheumatol 1995; 34: 334–42
Rau R, Sander O, den Broeder A, et al. Long-term efficacy and tolerability of weekly subcutaneous injections of the fully human anti-TNF antibody D2E7 in patients with rheumatoid arthritis. Arthritis Rheum 1998; 41(Suppl.): 55
Jones M, Symmons D, Finn J, et al. Does exposure to immunosuppressive therapy increase the 10 year malignancy and mortality risks in rheumatoid arthritis? A matched cohort study. Br J Rheumatol 1996; 35: 738–45
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Richard-Miceli, C., Dougados, M. Tumour Necrosis Factor-α Blockers in Rheumatoid Arthritis. BioDrugs 15, 251–259 (2001). https://doi.org/10.2165/00063030-200115040-00005
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DOI: https://doi.org/10.2165/00063030-200115040-00005