Recent developments in the use of biologics in psoriasis and autoimmune disorders. The role of autoantibodiesBMJ 2005; 330 doi: http://dx.doi.org/10.1136/bmj.330.7493.716 (Published 24 March 2005) Cite this as: BMJ 2005;330:716
- Silja Rott, resident1,
- Ulrich Mrowietz ([email protected]), associate professor1
- 1 Department of Dermatology, University of Kiel, 24105 Kiel, Germany
- Correspondence to: U Mrowietz
Treatment of autoimmune disorders such as psoriasis, rheumatoid arthritis, and Crohn's disease with so called biologics (selective immunomodulatory drugs) has become a standard way to treat severe or recalcitrant forms of these diseases. In particular, antagonists of tumour necrosis factor α (TNF-α) have been proved to be highly efficacious. In this review we summarise the current knowledge on problems associated with treatment with biologics, with particular emphasis on TNF-α inhibitors and autoantibody development. We also discuss the possible increased risk of lymphoma.
Monoclonal antibodies and fusion proteins have become an important group of drugs (known as biologic drugs) for treatment of chronic autoimmune disorders.w1 Advances in antibody engineering and new techniques have allowed the generation of fusion proteins and chimeric, humanised, and fully humanised monoclonal antibodies. Fourteen biologic drugs have already been approved in the United States (by the US Food and Drug Administration (FDA)) and in other countries; over 70 are in late stage clinical trials (at least phase II) and over 1000 in preclinical development.w2
Treatment with these agents is well established for patients with rheumatoid arthritis and Crohn's disease, and in recent years a major focus of research into new biologics was psoriasis, an inflammatory T cell mediated skin disease. In particular, inhibitors of TNF-α were found to be very effective in the treatment of chronic plaque-type psoriasis, pustular psoriasis, and psoriatic arthritis.w3-w5 The mechanism of action of these drugs is either binding free TNF-α to the soluble receptor-like fusion protein etanercept (Enbrel) or direct inhibition of TNF-α bioactivity with the monoclonal antibodies infliximab (chimeric, Remicade) or adalimumab (fully human, Humira).1–5 w6 Other biologics targeting activated T cells and/or their migration into the skin are alefacept (Amevive) and efalizumab (Raptiva). Alefacept is a dimeric fusion protein consisting of a CD2-binding portion …
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