What Are Tumor Necrosis Factor Inhibitors?

Tumor necrosis factor (TNF) inhibitors are a new class of biologic therapies that have changed the face of rheumatology over the past decade. TNF inhibitor therapy can lead to dramatic improvements in RA symptoms and prevent joint destruction. Unlike the typical arthritis drugs, which tend to be composed of small molecules, TNF inhibitors are complex antibodies (proteins) that are directed against the chemical signal that causes inflammation in your body.

Tumor necrosis factor (TNF) inhibitors have changed the face of rheumatology over the past decade. TNF inhibitor therapy can lead to dramatic improvements in RA symptoms and prevent joint destruction.

Tumor necrosis factor alpha (TNF-α) is a chemical that is produced by some of the white blood cells in your body during the immune response. It stimulates inflammation, which in turn helps to fight infection and repair damaged tissues in your body. In RA, the inflammatory process mediated by TNF-α gets out of control and results in the pain, redness, and swelling that is characteristic of RA. Scientific studies have shown that TNF-α is found in large quantities in the swollen joints of people with RA.

TNF inhibitors work by binding to the naturally produced TNF-α molecules in the joints and bloodstream. When the TNF inhibitor medication binds to TNF-α molecules, it renders them ineffective and removes them from the bloodstream. Without the stimulation of the TNF-α, the inflammation decreases and symptoms are reduced. In addition to reducing the signs and symptoms of RA, extensive medical studies have shown that TNF inhibitors can slow—or even stop completely—joint damage.

TNF inhibitors are administered either through intravenous infusion or by a subcutaneous injection. The time between injections can range from weeks to months, depending on the specific agent and the severity of your disease.

Currently, three TNF inhibitors are approved in the United States for the treatment of RA: infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). Several more TNF inhibitors are currently being reviewed by the FDA. All of these therapies are expensive, however, so you should find out which agents your insurance will cover and discuss this issue with your physician before beginning therapy.

TNF-α inhibitors suppress the immune system and can place you at higher risk for infections. Usually, these infections are minor infections of the upper respiratory or urinary tract and can be easily managed with antibiotics. Unfortunately, some life-threatening infections and deaths from infections have been associated TNF-α inhibitor use. Therefore, if you are taking one of these medications, you should not ignore signs of infection, such as fever, cough, headache, weakness, and abdominal or back pain, as they may be signs of a serious problem. Some physicians tell their patients that while they are taking TNF-α inhibitors, they are “not allowed to have a cold or flu!” That is, patients shouldn't assume that a mild cough or fever is “just a cold” but rather should contact their physician and make sure they are medically evaluated to prevent serious or life-threatening infections.

Cases of lymphoma and tuberculosis have also been associated with the use of all TNF-α inhibitors.

Over the past seven years I've used all three of these anti-TNF drugs. The first one I tried was Remicade. This product is given intravenously over a period of about 2-3 hours. It was such a production—I really didn't like it. It made me feel like a cancer patient receiving chemotherapy. This was a very depressing stage for me. In addition, the results after many treatments were not satisfactory. The next anti-TNF I tried was Humira. Humira is a medication that you can inject yourself, sort of like insulin. Unfortunately, a few hours after my first injection I developed a severe allergic reaction. I was covered in a rash from head to toe. It was incredibly uncomfortable—hot and itchy. My doctor had to put me on a heavy dose of steroids to counter the reaction. It took over a week for the rash to subside. Finally, about a year ago, my doctor suggested that I try Enbrel, another of the anti-TNF drugs.

I was so depressed when he told me this because again I would have to give myself an injection once a week—I had been through a year of injections with methotrexate and never got comfortable injecting myself. I felt I really had no choice because of my worsening symptoms. So I gave it a try and now a year later I can say the results have been fantastic. No more flare ups and very little swelling at all in my hands. Another great thing about Enbrel is that it comes in syringes that are pre-filled for you. This took away the anxiety I had with the whole process of giving myself methotrexate injections. I had to measure the right amount and was afraid of giving myself too much or too little. My rheumatologist told me that is not unusual for someone to try different anti-TNF medications till they find the one that works. Some people respond to Remicade and would rather have an intravenous infusion every eight weeks than inject themselves every week or two. Others prefer the autonomy of being able to inject themselves and not bother with spending several hours at the doctor's office. For others, it is an issue of which product their insurance will pay for. You should discuss these issues with your doctor before starting one of these anti-TNF agents.