Interleukins and Janus Kinases: Emerging Therapeutic Targets in Rheumatoid Arthritis

Treatment of rheumatoid arthritis (RA) has evolved from the use of conventional treatments, such as methotrexate, to disease-modifying biologic agents that can slow the disease process and make remission possible for some patients. Although these targeted therapies have improved the clinical management of patients with active RA, no current approach meets the goals of therapy for RA: slowing disease progression while improving the patient's well-being and, ideally, creating complete clinical remission that is verifiable by radiography and patient report. Consequently, investigators continue to look for additional drivers of RA and for interventions that will target specific pathways with few adverse effects. Aberrant helper T (Th)-cell activation has been implicated as a mechanism leading to several autoimmune diseases that seem to have common roots (RA, psoriatic arthritis, and Crohn's disease). Research into the pathophysiology of RA is focusing on Th cells, as well as molecules involved in intracellular signaling. Through kinase inhibition, it may be possible to interrupt signal transduction and potentially reduce proinflammatory cytokine production. Two promising targets are interleukins and Janus kinases. Oral inhibitors of interleukins or Janus kinases may enable more patients to achieve disease remission.