More recently, thanks to scientific breakthroughs in molecular biology and genetic engineering, we have a better understanding of the role of T cells, B cells, and chemical mediators in RA and other autoimmune diseases.  T-cells and B-cells, like the White House and The Pentagon, communicate with each other and give orders, let’s say to attack.  Tumor necrosis factor (TNF), IL-1, IL-6 or other cytokines, released from white blood cells after receiving the order, are key chemical mediators that can cause inflammation and joint damage.  However, if communication between T cells and B cells is interrupted, or if B cells are eliminated, inflammation and joint damage can be impeded and even prevented.

In 1974, W. Kohler and C. Milstein developed a process for generation of specific antibodies which can bind the target cells and chemical mediators.  Since then, researchers are able to produce the desired antibodies (biologics) for specific therapeutic purpose.  In the past decade, with the development of biologic drugs, the treatment of rheumatoid arthritis and other autoimmune diseases enters the new era.

The biological activity of TNF is mediated by binding TNF to receptors which then trigger the inflammatory cascade.  Like anti-missiles, anti-TNF agent can lock in on target (TNF) and block the enemy’s offensive maneuvers.  Currently, there are five anti-TNF agents including Enbrel, Humira, Remicade, Simponi and Cimza.  Anti-TNF agents can also be used to treat psoriatic arthritis, inflammatory bowel disease and ankylosing spondylitis.  Acterma and Kevzara (sarilumab), blocking IL-6 receptor are also effective treatment for RA.  Anakinra, blocking IL-1, is especially effective treatment for juvenile RA.

Finally, there are two other different types of biologics for treatment of RA.  The first is Orencia which inhibits the activation of T cells and helps relieve joint inflammation.  The second is Rituxan which targets and depletes B cells.  Rituxan is also approved for treatment of Wegener’s granulomatosis and microscopic polyangiitis.

In the past few years, the FDA has approved two oral biologics-Xelianz (tofacitinib) and Olumiant (baricitinib) for the treatment of RA.  Xelianz and Olumiant are oral JAK (Janus Kinase) inhibitors.  Unlike other biologics that target extracellular molecules, such as proinflammatory cytokines, Xelianz and Olumiant target the intracellular signaling pathways that operate as hubs in the inflammatory cytokines network.  Even though severe RA and other autoimmune diseases can be debilitating, the new biologic drugs give us good reason to be optimistic.

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