Biologics for Rheumatoid Arthritis Treatment

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In recent years, there have been promising advances in treating rheumatoid arthritis -- especially for those people who do not respond to disease-modifying drugs. The most important advance has been the development of a group of drugs called biologic response modifiers or biologics.

There are several biologics approved to treat arthritis. They include:

• Enbrel
• Humira
• Kineret
• Remicade
• Rituxan
• Orencia

There are also other biologics being studied to treat various forms of arthritis.

How Do These Drugs Work?

Biologics are genetically engineered proteins derived from human genes. They are designed to either inhibit or supplement specific components of the immune system called cytokines. These cytokines play a pivotal role in either fueling or suppressing inflammation (a key component in several forms of arthritis, such as rheumatoid arthritis and psoriatic arthritis).

Enbrel, Humira, and Remicade inhibit a cytokine called tumor necrosis factor or TNF. Kineret blocks the cytokine interleukin-1 (or IL-1). Rituxan selectively targets immune cells known as CD20-positive B cells.

What makes these biologics so different from other drugs used to treat rheumatoid arthritis that modify the immune system (see the DMARDs article) is that they affect a specific component of the immune system, not the entire immune system. Thus, these medications theoretically have fewer side effects.

What Are the Side Effects?

As with any drugs that suppress the immune system, biologic therapy might pose some risks, since it could make your body more vulnerable to other infections and diseases. Patients should seek immediate medical attention if they develop persistent fever.

Biologics may also cause some chronic diseases in remission -- such as tuberculosis -- to flare up, and they are often not recommended for people with multiple sclerosis and other conditions such as congestive heart failure. All patients should be skin tested for tuberculosis prior to starting biologics.

Since biologic therapy is only in its early stages of use, some of the long-term effects of using these medications simply aren't known, and your doctor will probably want to regularly monitor your health while using them. Biologics are also more expensive than conventional treatments. However, the evidence so far is that they work well and pose fewer risks than other systemic therapies.

One disadvantage to biologic medication is that it has to be given either by injection or by intravenous infusion; the latter approach can take two hours per session. However, the advantages of these drugs are significant.

Although animal studies have shown no effect on fertility or impairment of the fetus, these studies cannot always predict the effects in humans. Accordingly, pregnant women should receive these drugs only if clearly needed.

As a general rule, two biologic therapies should not be taken at the same time.

Researchers say that future agents, still in the early development stages, may be less expensive and will be taken orally. Also on the horizon are biologics that target different cytokines.

Here are some details on each drug:

Enbrel

Enbrel reduces joint inflammation by blocking a cytokine called tumor necrosis factor, or TNF.

Enbrel is given by self-injection under the skin once or twice a week. Many people learn to give their own injections or receive them from a family member who has received proper instruction. A kit is available from the manufacturer that makes drawing up the medicine and injecting it easier.

Enbrel may cause irritation at the injection site, which is diminished by applying a cold pack to the injection site prior to injection.

Enbrel's effect can also weaken the immune system. Although rare, some people have developed serious infections while taking Enbrel. Anyone with a serious infection should stop taking Enbrel and resume it after being advised by a doctor. If you develop an infection, let your doctor know immediately as you need to be monitored closely.

Pregnant women should not take Enbrel because the effects on a developing child are unknown.

Humira

Humira also blocks the cytokine tumor necrosis factor. The drug is an injection that can be self-administered. It is usually taken once every two weeks.

Rare cases of severe allergic reactions and blood cell deficiencies have occurred with Humira. Bruising or bleeding can be a sign of blood cell problems and should be reported to your doctor immediately.

In addition, serious infections have been seen in clinical trials when Humira was taken with the rheumatoid arthritis drug Kineret.

Kineret

Kineret reduces joint inflammation by blocking the cytokine interleukin-1. The drug is administered as one injection daily (can be self-injected or given to you by another individual). This is generally not widely used in practice because of low effectiveness rates.

Tell your doctor if you develop signs of an infection, such as fever.

Remicade

Like Enbrel and Humira, Remicade reduces inflammation by blocking the cytokine tumor necrosis factor. Remicade is given by intravenous infusion in the doctor's office or hospital. Each infusion takes about two hours. The intravenous treatments are given three times during the first six weeks of therapy, then every eight weeks. Remicade is given with methotrexate for treating RA.

As with other biologics, treatments may weaken the body's ability to fight infection. If you have any signs of infection such as a fever over 100F, sweats or chills, skin rash, or other symptoms that cause concern, contact your doctor right away.

With any treatment, it is important to meet with your doctor regularly so he or she can closely monitor you to detect the development of any side effects and monitor your treatment if necessary. Your doctor may periodically order blood tests or other tests to determine the effectiveness of your treatment and the presence of any side effects.

Rituxan

Rituxan is approved for patients with moderate-to-severe RA who have not improved with TNF antagonists, such as Enbrel or Remicade. Rituxan is given as two infusions in the vein -- separated by two weeks -- in combination with weekly methotrexate.

The most common side effects include infections and reactions while the medicine is given (called infusion reactions). Symptoms of infusion reactions include flu-like illness, fever, chills, nausea, and headache.

Orencia

Orencia is approved for the treatment of moderate to severe rheumatoid arthritis. Orencia blocks signals that are needed to activate T-cells of the immune system. Activated T-cells play an important role in the development of rheumatoid arthritis.

Orencia is approved to reduce the symptoms of RA in patients not helped by other biologics. It can be taken alone or with other medications except biologics.

Orencia is given by intravenous infusion. Adverse reactions include infection and serious allergic reaction. Patients shouldn't receive live vaccines while taking Orencia or within three months of stopping the drug. Caution should be used in prescribing Orencia for patients with chronic obstructive pulmonary disease (COPD). Those patients' respiratory health should be monitored. Orencia should be used during pregnancy only if clearly needed. Nursing mothers should talk to their doctors about the risks and benefits of taking Orencia.