Emerging therapies in the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease with a significant morbidity defined by marked destruction and deformity of joints. It is characterized by autoantibody production, synovial inflammation, and erosion of the cartilage and bone. The current first-line treatment for RA is methotrexate (MTX), an orally active disease-modifying anti-rheumatic drug (DMARD). Biologic DMARDs that target tumor necrosis factor (TNF) or other molecules have emerged as potent alternative therapies for patients with inadequate response to MTX therapy. Despite the huge success of MTX and/or biologics, there is still a significant unmet medical need in RA. Approximately one-third of RA patients are nonresponsive to currently available therapies. With their critical roles in mediating multiple inflammatory pathways, small-molecule tyrosine kinase (TK) inhibitors are gaining attention as candidates for oral RA drugs with positive outcomes for a number of late-stage clinical trials of small-molecule Jak (Tasocitinib) or Syk (fostamatinib) inhibitors. With the potential for attenuating multiple inflammatory pathways activated in RA, tasocitinib and fostamatinib may represent new and welcome additions to the RA therapeutic landscape. Drug Dev Res 72:805-816, 2011. (C) 2011 Wiley Periodicals, Inc.