JAK and SYK Inhibitors:
Controlling Immune System Signals

A kinase is an enzyme in the body involved in immune system functions. In diseases like RA, various pathways or signals between key cells can function abnormally, so researchers are looking at new treatments that may inhibit or “turn off” these improper signals.

Tofacitinib (Xeljanz) is an oral medicine approved by the FDA to treat RA in 2012. It’s intended to stop the Janus Associated Kinase, making it a JAK-inhibitor.

Researchers working on another drug, SB1578, reported favorable results in inhibiting the kinase JAK-2 at the annual ACR meeting in November. An early study of rats with RA treated with SB1578 showed the drug helped normalize cytokine levels. It is now involved in clinical trials recruiting human patients.

In addition to JAK inhibitors, investigators are also working on inhibiting the spleen tyrosine kinase (SYK). A Phase II study of the oral SYK-inhibitor fostamatinib reported in The New England Journal of Medicine in 2010 focused on 457 patients with active RA taking methotrexate as well. Around two-thirds of the patients showed significantly reduced disease activity by adding fostamatinib daily.  A new clinical trial of the drug comparing it to adalimumab (Humira) treatment for RA patients is currently recruiting participants.

More Ways to Control Rheumatoid Arthritis

Vitamin D, which the body absorbs through sun exposure and from foods like fish or fortified milk, is being studied for many health benefits. Vitamin D helps the body absorb and maintain levels of calcium. A group of U.S. and Canadian scientists published a study in 2010 that examines the benefits of intensive vitamin D therapy for RA patients. Many people with RA test low for vitamin D levels in their blood. This study of 89 RA patients showed that to maintain normal levels of vitamin D, people with RA may need to take much higher doses of supplements than the rest of the population.

Statins, a group of drugs widely used for lowering cholesterol and preventing heart disease, are being studied for their effectiveness in fighting inflammation and autoimmunity. An Israeli study published in 2010 showed that statin use may lower the risk of developing RA.

One group of researchers in California is working on a drug called ASP2408 that aims to decrease the production of inflammation-causing T-cells in RA more effectively. Part of a group of treatments called CTLA4-Ig therapies, which includes the RA drug abatacept (Orencia), this drug is in a Phase I clinical trial now.