News in the biological therapy of rheumatoid arthritis and future prospects
Authors:
L. Šenolt; J. Vencovský
Authors‘ workplace:
Revmatologický ústav a 1. LF UK, Praha
Published in:
Čes. Revmatol., 17, 2009, No. 1, p. 36-49.
Category:
Overview Reports
Overview
In recent years, up-to-date knowledge of pathogenetic mechanisms in rheumatoid arthritis contributed to establishment of biological therapy in clinical practice. For patients non-responsive to traditional disease modifying antirheumatic drugs, there are TNF-α inhibitors available. In case of their contraindication, lack of effect or adverse events, the treatment with B-lymphocyte depleting agent (rituximab) or with a drug blocking T-lymphocyte costimulation (abatacept) has been approved in rheumatoid arthritis. The progress in biotechnology manufacturing contributed to the development of several other perspective agents which may form the basis for the immunotherapy of rheumatoid arthritis in the near future. For instance, new or modified TNF-α inhibitors (golimumab, certolizumab pegol), and new monoclonal antibodies against other cytokines (e.g. IL-1, IL-6, IL-12, IL-15, IL-17, IL-23), and agents directed at B-lymphocyte depletion (e.g. ocrelizumab, ofatumumab) are in various stages of development. Many pharmaceutical companies put great expectations in small molecules with possible peroral administration. Nowadays, more than a half of new anti-inflammatory agents in the preclinical and clinical trials are represented by small molecules, which are recognised as potentially very promising drugs in rheumatoid arthritis. In most cases, theese are inhibitors of proteins which mediate the signalling and transcription of proinflammatory genes inside the cells. The increasing numbers of cytokine inhibitors and modulators of immune processes, which are in the current clinical trials, will further expand the spectrum of efficient therapies for patients with rheumatoid arthritis in the future.
Key words:
rheumatoid arthritis, biological therapy, clinical trials, monoclonal antibodies, small molecules
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