Biologic DMARDs- Targeted Therapy

Category: Medications & Supplementation Published on Monday, 13 April 2015 Written by Yong Tsai, MD

In the past few years, due to breakthroughs in genetic engineering and a better understanding of the role of T cells, B cells and chemical mediators in RA inflammation. Tumor necrosis factor-alpha (TNF), Interleukin-6 (IL-6), interleukin-1 (IL-1) and some other cytokines have proven to be the key chemical mediators which initiate, maintain and perpetuate inflammation and cause joint damage. The interaction of T cells and B cells also play a significant role in developing inflammatory cascade.

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. Like anti-missiles, they can lock in on a target and block the enemy's offensive maneuvers. Therefore, joint pain and damage can be impeded and even remission can be achieved in most patients. In the past decade, the treatment of rheumatoid arthritis and other autoimmune diseases enters the new era.

A state of the art weapon called biologic agents which can effectively block major chemical mediators-TNF alpha, has been developed. Five anti-TNF agents are etanercept (Enbrel), inflximab (Remicade), adalimumab (Humina), golimumab (Simponi), certolizumab pegol (Cimzia). Remicade is administered by intravenous infusion every 6-8 weeks. Enbrel is administered subcutaneously every week and Humina is administered every other week. Cimzia is administered subcutaneously once a month. Simponi is administered subcutaneously or IV infusion.

Due to high cost and insurance restriction, anti-TNF agents are currently limited for patients with poor response or inadequate response to two different DMARDs such as methotrexate or plaquenil. In general, combination MTX and anti-TNF treatment is much effective than MTX or anti-TNF treatment alone.

Another new biologic DMARD- tocilizumab (Actemra) which inhibit interleukin-6 is administered subcutaneously or IV infusion every month. Orencia can relieve joint inflammation by inhibiting activation of T-cells. If T cells are not activated, inflammation cannot initiate. Orencia can be administered subcutaneously or IV infusion. Another biologic DMARD-rituximab (Rituxan) which targets and depletes B cells is administered twice in 6 months. Abatacept, rituximab and tocilizumab are all effective in some patients with poor response or unsatisfactory response to anti-TNF treatment. Xeljanz (tofacitinib), a new oral DMARD was approved by FDA on November 6, 2012. JAKs are intracellular enzymes that regulate and transmit signals inside the cells.

Xeljanz works by inhibiting the JAK pathway-a signaling pathway inside cells that play a significant role in inflammation associated with RA. Xeljanz is considered a small –molecule drug, not a biologic agent and can be used as immunotherapy (alone) or combined with methotrexate or other non-biologic DMARDs. Xeljanz should not be used with biologic drugs or powerful immunosuppressants, such as azathioprine or cyclosporine.

Even though RA is a debilitating disease, these new drugs give us good reason to be optimistic. If it is treated early and properly, joint pain and swelling can be controlled and deformities can be prevented or minimized. Hopefully, soon, we will have the winning combination of fighting power to force RA into retreat and this "crippling arthritis" will become a thing of the past

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