Emerging Therapeutic Targets in Rheumatoid Arthritis

Advances in the understanding of the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA), have led to new treatments that improve quality of life.1 The use of empiric treatments, such as methotrexate (MTX), has given way to newer biologic therapies that target specific molecules and cellular structures known to be involved in the chronic inflammatory process. For some individuals, these disease-modifying biologic agents can slow or even reverse the deleterious physical effects associated with RA, making remission possible. Nevertheless, despite the availability of various biologic agents for the treatment of RA, some patients do not achieve the desired response, do not maintain treatment responses over time, or experience intolerable adverse effects (AEs) that lead to treatment discontinuation. In addition, these treatments can be expensive and require subcutaneous (SC) or intravenous (IV) administration. This unmet need has prompted investigation into alternative drivers of RA pathogenesis that may serve as therapeutic targets.1

Ongoing research is focusing on molecules that are involved in intracellular signaling following ligand binding to receptors on inflammatory cells.1 Through inhibition of 1 or more of the kinases involved in signal transduction, it may be possible to interrupt intracellular signaling, modulate the function of cellular structures, and subdue the inflammatory process.

Currently, investigators are exploring 2 promising targets in RA: interleukins (ILs) and intracellular Janus kinases (JAKs). Small molecular agents targeting IL-17, such as secukinumab and ixekizumab, are already being used clinically for patients with psoriatic arthritis, plaque psoriasis, and ankylosing spondylitis.2,3 Tofacitinib, an oral JAK inhibitor, is approved for RA unresponsive or intolerant to MTX.4

The Interleukin-Cytokine Family

Intracellular signaling pathways transmit information regulating cellular responses and gene transcription to the…

Read the full article from the source…

Back to Top