New drugs emerge for rheumatoid arthritis
Published: Monday, December 10, 2012 at 5:30 a.m.
Last Modified: Sunday, December 9, 2012 at 3:18 p.m.
Rheumatoid arthritis is a chronic progressive inflammatory arthritis and autoimmune disease that occurs when our immune system (T-cells, B-cells and other immune cells) goes astray, mistaking our own joint tissue for a foreign invader, attacking it and causing inflammation. When the inflammatory process advances, chemical mediators can damage cartilage, bone and ligament, causing joint deformities and impaired function.
Due to the understanding of pathogenesis of rheumatoid arthritis, known as RA, the strategic plan in treating it has changed from a conventional method of using nonsteroidal anti-inflammatory drugs and corticosteroids to control symptoms, to so-called disease-modifying anti-rheumatic drugs such as methotrexate, to further alter the inflammatory process and slow down joint damage.
In the past 10 years, thanks to scientific breakthroughs in molecular biology, we have a better understanding of the role of T-cells, B-cells, enzymes called JAKs and chemical mediators in RA.
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 pro-inflammatory cytokines, released from white blood cells (extracellular) after receiving the order, are key chemical mediators that can cause inflammation and joint damage.
JAKs are a family of protein tyrosine kinases in the cytoplasm of cells (intracellular). When activated, JAKs stimulate a cascade involved in the production of pro-inflammatory cytokines. However, if these chemical mediators are blocked, if communication between T-cells and B-cells or the JAK pathway is interrupted, or if B cells are eliminated, inflammation and joint damage can be impeded and even prevented. The biological activity of TNF is mediated by binding TNF to receptors, which triggers the inflammatory cascade. Currently, there are five anti-TNF agents — Enbrel, Humira, Simponi, Cimzia and Remicade — that can effectively block TNF molecules. Like anti-missiles, anti-TNF agents can lock in on a target and block the enemy's offensive maneuvers. All anti-TNF agents are similar but not the same. Another biologic agent, Actemra is used for targeting another inflammatory cytokine, IL-6. Actemra has similar effectiveness as anti-TNF agents.
There are other types of biologic agents. A T-cell co-stimulation modulator, known as Orencia, helps relieve joint inflammation by inhibiting activation of T-cells. A biologic agent called Rituxan targets and depletes B cells. Tofacitinib (marketed as Xeljanz) is a small-molecule inhibitor of the Janus kinase and was just approved for RA last month. All biologic agents and new JAK inhibitors are effective in treating RA patients who have not responded adequately to methotrexate or other disease modifying anti-rheumatic drugs. But all new drugs are extremely expensive and must be approved by a patient's insurance plan prior to treatment.
Even though RA is a debilitating disease, these new drugs give us good reason to be optimistic.
Dr. Yong H. Tsai is board-certified in rheumatology, allergy and clinical immunology and has been practicing in this area since 1993. Send questions to Dr. Tsai in care of email@example.com. You also can check his website: arthritis-allergy.net.
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