At the horizon of innovative therapy in rheumatology: new biologic agents.
OBJECTIVE
To review the rational and the results regarding the use of novel biologic agents in inflammatory rheumatic diseases.


RESULTS
Recent findings show that excessive IL-1 processing and release contribute to different rheumatic conditions, including periodic fever syndromes, systemic-onset juvenile idiopathic arthritis, adult Still's disease, and crystal-induced arthritis. Preliminary results indicate that administration of IL-1 receptor antagonist and other IL-1 inhibitors improves these conditions. IL-6 also plays a major role in the control of inflammatory responses. Several clinical trials have shown that inhibition of IL-6 by a monoclonal antibody against its receptor is efficacious in rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis patients. Accumulating evidence indicates that other cytokines, including IL-15, IL-18, and IL-21 may also play an important role in rheumatoid arthritis. Several signaling pathways involved in the immune and inflammatory responses may also constitute novel targets. Preliminary data on an agent targeting the Janus kinase/Signal transducer and activators of transcription pathway are encouraging.


CONCLUSIONS
Beyond tumor necrosis factor alpha targeting, the use of inhibitors against other cytokines and cytokine-induced intracellular responses is leading to a promising therapy in the future.
Finckh
Axel
A
Division of Rheumatology, University Hospitals of Geneva and University of Geneva, Switzerland.
Gabay
Cem
C
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use; D007378:Interleukins / Q000276:immunology; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors*; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D007378:Interleukins; D018123:Receptors, Interleukin