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Clinical trials on biologics in rheumatoid arthritis
Background:
Cytokines and T cells play a major role in the pathogenesis of rheumatoid arthritis (RA). Biologic targeting is a novel therapeutic approach. Published trials in humans are discussed in this paper.
Methods:
CD4-positive T cells, proinflammatory cytokines like TNF-alpha, IL-1, IL-6 and gamma-IFN were major targets for therapy. Biologics were constructed of monoclonal human and non-human antibodies, chimerics of both, antiinflammatory regulatory proteins like IL-1 receptor antagonist, IL-10, and fusion proteins consisting of receptors and immunoglobulins.
Results:
More than 2000 humans with RA were exposed to biologics in the last decade. Both, toxic and safe, efficient and non-efficient drugs were tested. Phase II data could not confirm preliminary phase I data in several drugs tested. The pharmacokinetic profile of biologics is influenced by frequent induction of human anti drug antibodies.
Conclusion:
The major role of cytokines in RA has been confirmed. Due to the limited long-term experience immunomodulation does not replace conventional pharmacotherapy.