DEAR MAYO CLINIC: I've heard of doctors using TNF inhibitors to treat rheumatoid arthritis. What exactly are TNF inhibitors and are they safe to use?

ANSWER: An estimated 1.3 million people in the U.S. have rheumatoid arthritis, an inflammatory disease that causes pain, swelling, stiffness, damage and loss of function in the joints. For some time, treatment options were limited to drugs that curbed pain and reduced inflammation.

Today, more powerful drugs are available that can reduce or even prevent the joint damage caused by rheumatoid arthritis. Chief among these drugs are tumor necrosis factor (TNF) inhibitors. Although these injectable drugs have been hailed as a major advance in treatment, concerns have long been raised about the risks associated with their use.

TNF inhibitors are powerful drugs that inhibit the activity of tumor necrosis factor, or TNF, a protein that triggers inflammation in the body. They fall under a category of drugs known as biologic response modifiers, which are designed to selectively block parts of the immune system that play a role in inflammation. Although there are a number of them now, TNF drugs are, by far, the most commonly used drugs of this type. The first one was introduced in 1998 and now there are five on the U.S. market: etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), golimumab (Simponi) and certolizumab (Cimzia).

About one-third of people with rheumatoid arthritis are probably on a TNF drug or have been on one at some point. Generally, these drugs are prescribed for those who have severe and persistently active forms of the disease. They typically aren't used as a first line treatment. In fact, many people do well with more conventional, older drugs. But if a patient is not doing well, we can add a TNF drug. Very often, TNF drugs are used in combination with methotrexate (Rheumatrex), a disease-modifying antirheumatic drug, or DMARD, which can slow the progression of rheumatoid arthritis.

TNF drugs have been a blessing for many people with severe rheumatoid arthritis. That's because these drugs can effectively limit joint damage, allowing people to continue working and lead a normal life. These drugs may even help some people live longer.

However, TNF drugs do need to be used with caution. The major concerns are with infection and cancer. Research shows that people with rheumatoid arthritis have about double the risk of infection than does the average person, regardless of treatment. They probably have an increased risk of certain cancers, as well. But there's a slightly increased additional risk of infection with TNF drugs because they alter the immune system.

Any kind of infection is possible, but the biggest problem we've seen is with tuberculosis. To prevent the reactivation of a tuberculosis infection, we now screen people for the disease before prescribing a TNF drug.

With cancer, it's less straightforward. It's possible that there's an increased risk of blood cancers, such as lymphoma. There's also pretty good evidence that the risk of nonmelanoma skin cancers is higher in those taking TNF drugs.

Fortunately, there are a lot of people who've been on TNF drugs for many years without any problems. As with any kind of drug, it's a matter of working with your doctor to weigh the potential risks and benefits. -- Eric Matteson, M.D., Mayo Clinic, Rochester, Minn.

 

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