Treatment of rheumatoid arthritis: new therapeutic approaches with biological agents.
Rheumatoid arthritis is a chronic polyarthritis leading to joint destruction and remarkable disability. Current therapies have various degrees of efficacy, but toxicity frequently limits their long-term use. Furthermore, treatment of refractory rheumatoid arthritis includes increasing disease-modifying antirheumatic drugs dosage, using combination therapy, and adding or increasing the posology of corticosteroids. Although the etiology of the disease remains unknown, our increasing knowledge of the mechanisms underlying pathogenic events in rheumatoid synovitis, has provided opportunities to specifically target cell surface markers or cytokines involved in the inflammatory response. The objective of this review is to describe the different therapeutic approaches with biological agents that are either being utilized or are under development. Some of these products reflect the evolving capacity for the biotechnology industry to synthesize and humanize therapeutic agents: anti-tumor necrosis factor (TNF) alpha monoclonal antibodies (MoAb) and recombinant TNF-receptor construct appear to be validated tools. These treatments alone, or in combination with methotrexate are very effective in rheumatoid patients. Data from clinical trials and issues related to mechanisms of action, potential toxicity, and future perspectives for these novel therapeutic options are considered in this review. Anti-cytokine treatment include other interesting approaches to interfere with on-going inflammatory processes, such as the use of recombinant human interleukin (IL)1 receptor antagonist, or recombinant human IL10. T cell constimulatory blockade, induction of apoptosis in the synovial tissue, and gene therapy could represent future strategies in rheumatoid disease.
Afeltra
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Department of Clinical Medicine, First Faculty of Medicine, University of Rome La Sapienza, Viale del Policlinico-00161, Rome, Italy. aafeltra@tin.it
D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000502:physiology; D005805:Genes, MHC Class I / Q000235:genetics; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007596:Joints / Q000473:pathology; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000187:drug effects; D014611:Vaccination
D016207:Cytokines; D007155:Immunologic Factors; D018121:Receptors, Cytokine