Monoclonal antibody therapy rheumatoid arthritis

Rankin ECC, Isenberg DA. Monoclonal antibody therapy in rheumatoid arthritis. An update on recent progress. Clin Immunother 1996 6 143-53. 

Bayry J, Siberil S, Triebel F, et al. Rescuing CD4-FCD25-F regulatory T-cell functions in rheumatoid arthritis by cytokine-targeted monoclonal antibody therapy. Drug Discov Today. 2007 12 548-552. 

Isaacs JD, Watts RA, Hazleman BL, Hale G, Keogan MT, Cobbold SP, Waldmann H. Humanised monoclonal antibody therapy for rheumatoid arthritis. Lancet 1992 340 748-752. 

Keystone, E. C., Kavanaugh, A. E., Sharp, J. T., et al. (2004) Radiographic, cUnical, and functional outcomes of treatment with adaUmumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy a randomized, placebo-controUed, 52-week trial. Arthritis and Rheumatism. 50, 1400-1411. 

A variety of medical conditions are now believed to be caused or exacerbated by overproduction of certain cytokines in the body. A variety of pro-inflammatory cytokines, including IL-6 and IL-8 as well as TNF, have been implicated in the pathogenesis of both septic shock and rheumatoid arthritis. Inhibiting the biological activity of such cytokines may provide effective therapies for such conditions. This may be achieved by administration of monoclonal antibodies raised against the target cytokine, or administration of soluble forms of its receptor which will compete with cell surface receptors for cytokine binding. 

Elliott, M. J., Maini, R. N., Feldmann, M., Long-Fox, A., Charles, P., Bijl, H., and Woody, J. N. (1994). Repeated therapy with monoclonal antibody to tumour necrosis factor a (cA2) in patients with rheumatoid arthritis. Lancet 344, 1125-1127. 

Tesser, J. R. P., Wiesenhutter, C., Levy, R., Schiff, M., Lipani, J., Solinger, A., Mac Donald, B., Elliott, M., and Sing, K (1997). Tratment of rheumatoid arthritis with a primatized anti-CD4 monoclonal antibody, SB-210396 (DEC-CE9.1) Results of an open label extension study in patients responding to induction therapy. Arthritis Rheum. 40 (Suppl 9), S224. 

The first therapeutic antibody approved (Orthoclone OKT-3 or Muromonab CD3, 1986) was indicated not for cancer treatment, but for controlling acute rejection of transplanted organs (kidney, heart, and liver). Nowadays, other clinical indications such as asthma, rheumatoid arthritis, psoriasis, and Crohn s disease are treated with mAbs (see Chapter 17) (Antibody Engineering and Manufacture, 2005 Monoclonal Antibodies and Therapies, 2004 Hot Drugs, 2004 Walsh, 2004). 

Another TNFa monoclonal antibody known as etanercept (a fusion protein of human IgG and two p75 TNF receptors) [98] that is a competitive inhibitor of TNF s cell-surface receptor has been developed. Clinical studies have shown that etanercept therapy results in significant clinical benefits and is well tolerated and safe for long-term use [99-101]. Etanercept is given subcutaneously (25 mg) twice weekly for the treatment of rheumatoid arthritis [98]. It is also used in the treatment of psoriatic arthritis, and a recent clinical trial has reported that in addition to decreasing joint pain and fatigue, etanercept also decreases symptoms of depression associated with this chronic disease [102]. 

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