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Rheumatoid Arthritis (cont.)

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What are newer rheumatoid arthritis medical treatments?

Newer "second-line" drugs (DMARDs) for the treatment of rheumatoid arthritis include leflunomide (Arava) and the "biologic" medications etanercept (Enbrel), infliximab (Remicade), anakinra (Kineret), adalimumab (Humira), rituximab (Rituxan), abatacept (Orencia), golimumab (Simponi), certolizumab pegol (Cimzia), tocilizumab (Actemra), and JAK inhibitors represented by tofacitinib (Xeljanz). Each of these medications can increase the risk for infections, and the development of any infections should be reported to the health-care professional when taking these newer second-line drugs.

Leflunomide (Arava) is available to relieve the symptoms and halt the progression of the disease. It seems to work by blocking the action of an important enzyme that has a role in immune activation. Leflunomide can cause liver disease, diarrhea, hair loss, and/or rash in some people. It should not be taken just before or during pregnancy because of possible birth defects and is generally avoided in women who might become pregnant.

Biologic DMARDs represent a novel approach to the treatment of rheumatoid arthritis and are products of modern biotechnology. These are referred to as the biologic medications or biological response modifiers. In comparison with traditional DMARDs, the biologic medications have a much more rapid onset of action and can have powerful effects on stopping progressive joint damage. In general, their methods of action are also more directed, defined, and targeted.

Etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol are biologic medications that intercept a messenger protein in the joints (tumor necrosis factor or TNF) that promotes inflammation of the joints in rheumatoid arthritis. These TNF-blockers intercept TNF before it can act on its natural receptor to "switch on" the process of inflammation. This effectively blocks the TNF inflammation messenger from recruiting the cells of inflammation. Symptoms can be significantly, and often rapidly, improved in those using these drugs. Etanercept must be injected subcutaneously once or twice a week. Infliximab is given by infusion directly into a vein (intravenously). Adalimumab is injected subcutaneously either every other week or weekly. Golimumab is injected subcutaneously on a monthly basis. Certolizumab pegol is injected subcutaneously every two to four weeks. Each of these medications is being evaluated by health care professionals in practice to determine what role they may have in treating patients in various stages of rheumatoid arthritis. Research has shown that biological response modifiers also prevent the progressive joint destruction of rheumatoid arthritis. They are currently recommended for use after other second-line medications have not been effective. The biological response modifiers (TNF-inhibitors) are expensive treatments. They are also frequently used in combination with methotrexate and other DMARDs. Furthermore, it should be noted that the TNF-blocking biologics all are more effective when combined with methotrexate. These medications should be avoided by people with significant congestive heart failure or demyelinating diseases (such as multiple sclerosis) because they can worsen these medical conditions.

Anakinra (Kineret) is another biologic DMARD treatment that is used to treat moderate to severe rheumatoid arthritis. Anakinra works by binding to a cell messenger protein (IL-1, a pro-inflammatory cytokine). Anakinra is injected under the skin daily. Anakinra can be used alone or with other DMARDs. The response rate of anakinra does not seem to be as high as with other biologic medications.

Rituximab (Rituxan) is an antibody that was first used to treat lymphoma, a cancer of the lymph nodes. Rituximab can be effective in treating autoimmune diseases like rheumatoid arthritis because it depletes B-cells, which are important cells of inflammation and in the production of abnormal antibodies that are common in these medical conditions. Rituximab is used to treat moderate to severely active rheumatoid arthritis in patients who have failed treatment with the TNF-blocking biologics. Preliminary studies have shown that Rituximab was also found to be beneficial in treating severe rheumatoid arthritis complicated by blood vessel inflammation (vasculitis) and cryoglobulinemia. Rituximab is an intravenous infusion given in two doses, two weeks apart, approximately every six months.

Abatacept (Orencia) is a biologic medication that blocks T-cell activation. Abatacept is used to treat adult patients who have failed treatment with a traditional DMARD medication. Abatacept is an intravenous infusion given monthly or a weekly subcutaneous injection.

Tocilizumab (Actemra) is approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Tocilizumab is the first approved biologic medication that blocks interleukin-6 (IL-6), which is a chemical messenger of the inflammation of rheumatoid arthritis. Tocilizumab is an intravenous infusion given monthly or a weekly subcutaneous injection.

Tofacitinib (Xeljanz) is the first in a new class of medications used to treat rheumatoid arthritis called JAK inhibitors. Tofacitinib is used to treat adults with moderately to severely active rheumatoid arthritis in which methotrexate did not work well. Tofacitinib can be used with or without methotrexate. This prescription medicine is taken by mouth twice daily. Tofacitinib is considered a "targeted" medication that specifically blocks special enzymes of inflammation in joints (called Janus kinase) within cells. Tofacitinib is, therefore, referred to as a JAK inhibitor.

While biologic medications are often combined with traditional DMARDs in the treatment of rheumatoid arthritis, they are generally not used with other biologic medications because of the unacceptable risk for serious infections. Similarly, JAK inhibitor medication is not used with traditional biologic medications.

Medically Reviewed by a Doctor on 11/16/2017



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