Emerging targets of biologic therapies for rheumatoid arthritis.
Advances in molecular biology and the clinical success of strategies that target tumor necrosis factor (TNF) have led to further research into the pathophysiology of human rheumatoid arthritis. Several novel therapeutic targets have emerged from these efforts, including not only molecules that regulate TNF (e.g. TNF-alpha converting enzyme), the complex cytokine network (e.g. interleukin [IL]-6, IL-15, IL-17) and several adipokines, but also targets that originate from cellular and subcellular components of the disease. Strategies that aim at cellular targets include antibodies to CD20 or BLyS (also known as TNF ligand family member 13b), which deplete or inhibit B cells, as well as approaches that interfere with membrane-derived microparticles. Components of subcellular pathways, which are predominantly upstream of the central regulator of transcription nuclear factor kappaB, have also been studied. Of these, strategies that target mitogen-activated protein kinases have a leading role and are on the verge of clinical use; approaches that target specific molecules such as Janus kinases, signal transducer and activator of transcription proteins, and suppressor of cytokine signaling proteins also seem to show promise and might have a clinical application in the future.
Tarner
Ingo H
IH
Department of Internal Medicine and Rheumatology, Justus-Liebig-University of Giessen, and Division of Rheumatology and Clinical Immunology at the Kerckhoff-Klinik Bad Nauheim, Germany.
Müller-Ladner
Ulf
U
Gay
Steffen
S
D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D003165:Complement System Proteins / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000187:drug effects*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects*
D018501:Antirheumatic Agents; D016207:Cytokines; D003165:Complement System Proteins