Biological response modifiers, also called biologics, are a type of DMARD designed to alter the function of cytokines, signaling molecules that help mount an inflammatory reaction. These drugs may be able to do what other drugs have failed to do so far: stop the rate of joint deterioration.
Anti-TNF agents. These drugs block the action of tumor necrosis factor (TNF), which appears to play a pivotal role in joint inflammation (see Figure below). Five anti-TNF agents are now available: adalimumab (Humira), certolizumab (Cimzia), etanercept (Enbrel), infliximab (Remicade), and golimumab (Simponi). About 60% to 70% of people with rheumatoid arthritis respond well to anti-TNF agents.
How Anti-TNF Agents Work
When the immune system attacks the body's own cells, autoimmune conditions such as rheumatoid arthritis can develop, triggering inflammation and destruction of tissues. One of the chemical messengers involved in inflammation is tumor necrosis factor (TNF). TNF binds to normal joint tissues and increases inflammation (A). But an anti-TNF drug binds to the receptor sites on the joint tissue cells, blocking the TNF from causing destructive inflammation (B).
In a number of people with rheumatoid arthritis, these drugs have induced something close to remission. However, like anti-cancer chemotherapy, these drugs are potent and expensive. In addition, infliximab requires frequent visits to the hospital for infusions. As such, anti-TNF agents may be too aggressive for people with a mild or benign form of rheumatoid arthritis. And not everyone with rheumatoid arthritis responds to anti-TNF therapy. Even those who do may find their disease flares up again once therapy is stopped. For these reasons, most experts recommend that anti-TNFs be used only when first-line treatment with methotrexate or some other DMARD fails.
Anti-TNF agents are often used in combination with methotrexate to benefit people with active rheumatoid arthritis whose symptoms don't respond to methotrexate alone. These medications are taken by intravenous infusion or injection (see Appendix for more details). Several studies have shown that patients with moderate to severe disease who combine methotrexate and anti-TNF treatment have fewer symptoms and less joint destruction, especially if the treatment begins early. In a 2008 study published in The Lancet, people who received the drug combination of methotrexate plus etanercept were almost twice as likely to be free of symptoms and were also more likely to show no signs of progressive joint destruction in x-rays compared with people who took methotrexate alone. People who received the drug combination were nearly three times more likely to remain able to work.
A comment accompanying the report cautioned, however, that patients should consider whether the benefits of the combined therapy are great enough to warrant the additional expense, hassle, and potential harmful effects.
In rare cases, anti-TNF therapy has been associated with long-term neurological side effects, including numbness, tingling, and weakness. These symptoms may mimic multiple sclerosis (MS), so people with MS are generally advised not to take anti-TNF drugs. These drugs have also been linked to tuberculosis (especially in people previously exposed to the infection) and fungal lung infections such as histoplasmosis. Infliximab should not be taken by anyone with heart failure.
Other immune system modulators. These four medications target different parts of the immune system to dampen inflammation. Some are given to people who haven't responded well to DMARDs, but they are often given in combination with a DMARD (often methotrexate) to boost effectiveness.
Abatacept (Orencia) keeps the immune system from attacking healthy tissues by interfering with T cell activation. The most common side effects with abatacept include headache, upper respiratory tract infection, sore throat, and nausea. Abatacept can also make you more vulnerable to infections (including pneumonia) or make an existing infection worse. Some people develop an allergic reaction, which takes the form of a rash and fever. If serious, the reaction may require emergency medical help.