The Young and the RA

Tumor-necrosis factor (TNF) modifiers are some of the latest major breakthroughs in treating RA. The current TNF modifiers on the market are infliximab (Remicade), etanercept (Enbrel) and adalimumab (Humira). These drugs are genetically engineered and work by interfering with your bodies TNF, an immune factor that plays an important part in the disease-fighting process.

Studies done on TNF modifiers, a type of biologic drug, have shown that they all work fairly quickly and show significant improvements for those with RA. Often, as with other biologics, TNF modifers are combined with methotrexate to help increase their effectiveness. Combining a biologic with methotrexate also has the benefit of showing fewer side effects than using a higher dose of methotrexate alone.

While Remicade, Enbrel and Humira block TNF, they do differ in some ways, and it is important to know about them and realize what works best for you.

“Enercept (Enbrel) is a protein made from the fusion of two TNF receptors. The end product mimics their effects, which neutralize TNF. A 2002 two-year study suggested it is superior to methotrexate in slowing RA disease progression and has fewer side effects. It has been approved for RA, juvenile RA, and psoriatic arthritis.

“Inflixamab (Remicade) and adalimumab (Humira) are both monoclonal antibodies (MAbs), which are specially designed antibodies that target TNF. In one study, infliximab was superior to methotrexate, gold, corticosteroids, and a interleukin-1 receptor antagonist. Humira, the latest TNF modifier is the first fully human anti-TNF MAb, which may reduce some of the problems of infliximab” (About.com).

Like other RA drug, TNF modifiers do not cure RA — it is important to realize that there is currently no cure for RA. TNF modifiers have shown some evidence that they slow and may even halt joint erosion. These drugs are fairly expensive, however, and can cost over a thousand dollars a month.

There are side effects of TNF modifiers, though, and it is important to be aware of them. TNF modifiers can increase the risk of certain fungal and mycobacterial infections, including tuberculosis, because these drugs work by inhibiting the immune system. But since TNF modifiers target precise molecular targets, they don’t have as many widespread effects on the body. The side effects of the three drugs I mentioned above are similar, but can differ:

• “The most common adverse effects of all three are minor reactions at the injection site, but there are few other immediate side effects.
• Because these agents affect immune factors, there is some risk for severe infections particularly in susceptible individuals, such as those with uncontrolled diabetes, people taking other immunosuppressants, or anyone with a current active infection. For example, cases of tuberculosis and histoplasmosis (a fungal infection in the lungs) have been reported in patients taking TNF-modifiers. (While millions of healthy people unknowingly carry the TB organism, it rarely becomes active in those with healthy immune systems.) RA patients should be tested for TB before initiating treatment. It is not yet known if adalimumab poses as high a risk as infliximab.
• There have been a few reports of aplastic anemia.
• In rare cases, both etanercept and infliximab have been associated with nerve damage that resembles the disease process in multiple sclerosis. This involves demyelination (the loss of myelin, the insulation coat over nerve fibers) and can result in confusion, numbness, changes in vision, and difficulty walking.
• According to some experts, patients with multiple sclerosis should avoid these agents until further research is complete. (The effects of adalimumab are not known yet.)
• There have been reports of a lupus-like symptoms in a few patients taking etanercept, which resolved when the drug was stopped.
• Many patients develop an immune reaction to infliximab itself, which makes the drug less effective overtime. Nevertheless, in one study, benefits persisted for at least two years after stopping the drug.
• Although adalimumab is a similar agent, it is a fully human molecule and, therefore, may not provoke the immune response that infliximab does. Long-term studies are needed to confirm this.
• Infliximab has been linked to a few deaths in patients with pre-existing congestive heart failure.
• There is some suggestion that anti-TNF drugs increase the risk for lymphomas” (About.com).

So now you have all the information you need to know about TNF modifiers. It is important, however to be aware that there are other biologics out there, such as Kineret and Orencia, but I’ll talk more about them another time.

Until next time,

S.P.