Rheumatoid Arthritis


Rheumatoid Arthritis

About Rheumatoid Arthritis

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Sometimes, for unclear reasons, the immune system turns against the body and attacks it. This process is called autoimmunity. Rheumatoid arthritis is one of many different autoimmune diseases. In rheumatoid arthritis, the immune system attacks tissue inside the joints, causing inflammation, pain, joint damage, and ultimately joint destruction. By blocking certain components of the immune system, biologics help stop or reduce the inflammation caused by the misdirected attack.

Common Symptoms

Rheumatoid arthritis is characterized by pain, swelling, and inflammation of the joints. It most commonly starts in the small joints of the hands and feet. Eventually all joints can be affected. Your joints can feel stiff, particularly in the morning. Symptoms often come and go, and are often accompanied by fever or feeling tired or unwell. As the disease progresses, sufferers can experience severe joint damage and fatigue, making it difficult for them to complete everyday tasks. Flare-ups of rheumatoid arthritis are often unpredictable and difficult to manage. Pain, stiffness, and swelling are worse on some days and easier to bear on others.

Rheumatoid arthritis can be difficult to diagnose because many other conditions can cause joint stiffness, pain, swelling, and inflammation.

Your doctor will ask you about your symptoms and run a series of tests to confirm the diagnosis. Common blood tests your doctor might run include rheumatoid factor and anti-CCP antibodies. These are antibodies that eight out of 10 people with rheumatoid arthritis carry in their blood. Both rheumatoid factor and anti-CCP antibodies can also be found in one out of 20 people without rheumatoid arthritis, so these tests cannot confirm rheumatoid arthritis. Other tests include the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). These can help determine the degree of inflammation in your body. Another common test analyzes X-ray images of your hands to identify joint damage.

What Causes It?

The exact cause of rheumatoid arthritis is unknown. Some studies show that rheumatoid arthritis may run in families, suggesting a genetic component, yet having a family member who suffers from rheumatoid arthritis does not necessarily mean that you will also develop the disease.

Am I at Risk?

About 1.3 million adults suffer from rheumatoid arthritis in the United States, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The disease generally develops in people between 30 and 55 years of age, though it's most common after age 40. For reasons that remain unclear, women develop it more often than men. In some cases, rheumatoid arthritis can also affect children or older adults. If it is not adequately treated, it will often lead to joint destruction, disability, and a reduced quality of life

Are They Effective?

For many people who have not responded to standard rheumatoid arthritis treatment (conventional DMARDs, for example), the biologics can be effective treatments. However, people’s responses vary—some experience a vast improvement in their symptoms and function, while others may experience little or no improvement at all. It is important to note that the studies of biologics have involved people who had failed on other rheumatoid arthritis medication. 

These drugs cannot cure rheumatoid arthritis, but they have been shown to help relieve symptoms in about 30 to 70 percent of people who use them. The available evidence is not good enough to distinguish differences in the effectiveness of the biologics. So the main difference between these medications comes down to their safety profile or the side effects they cause. For example, anakinra (Kineret) has the highest rate of injection site reactions and is less commonly used to treat rheumatoid arthritis. Rituximab (Rituxan) causes more infusion reactions than the other biologics, and certolizumab (Cimzia) might have higher rates of serious infections.

That leaves six remaining biologics. There is more evidence overall on three—adalimumab (Humira), etancercept (Enbrel), and infliximab (Remicade). A large study—known as the DREAM study—used patient records to evaluate these medications in people who were not helped by taking conventional DMARDs. Humira and Enbrel appeared to be equally effective in treating rheumatoid arthritis. Also, similar numbers of people stopped taking each drug due to side effects, suggesting both drugs have similar side effect profiles.

The DREAM study also compared Humira to Remicade. The two drugs were similar in effectiveness, but Humira had a lower rate of people dropping out due to side effects. The DREAM study was not a randomized, controlled clinical trial, since it was based on patient records, so the results are not as robust as they would be if this had been a clinical trial.

Are They Safe?

Side effects are an important consideration with this group of biologics. In studies, people who took a biologic had a higher risk—13% versus 12%—of experiencing a serious life-threatening allergic reaction, infection, lymphoma, or other serious side effect than those who took a placebo. The serious or potentially life-threatening infections include bacterial infections, such as tuberculosis, pneumonia, or staph, and serious fungal infections. Minor side effects can also occur, but usually do not require stopping or changing drugs.

Mild Side Effects

  • Diarrhea
  • Headache
  • Injection site reactions
  • Nausea
  • Respiratory infection
  • Urinary tract infection 

Serious Side Effects 

  • Allergic reactions
  • Liver damage
  • Lymphoma
  • Serious infections

All of the biologics carry warnings on their labeling about serious side effects, particularly serious infections.

Rituxan appears to have a higher potential for infusion reactions than other biologics. In addition, it has been linked to an increased risk of a serious viral infection of the brain. The infusion reactions can be severe and even fatal. Because of this, it should only be used as a second-line therapy if other biologics do not provide enough symptom relief.

Remicade has been shown to have a high rate of serious side effects, and is also not one of the top picks. One trial found that, compared to Orencia, Remicade had higher rates of serious adverse events (18.2 percent compared with 9.6 percent), and serious infections (8.5 percent compared with 1.9 percent).

The available evidence indicates that Orencia and Kineret have the lowest risk of serious side effects. However, Kineret, which is given as an injection under the skin every day, causes more redness, itching, rash, and pain at the injection site than the other biologics that are given in this way.

Biologics are also associated with an increased risk of skin cancers. It was previously thought that the biologics might also increase the risk of cancers involving lymph nodes and bone marrow, but data from multiple studies has not shown this to be the case. However, the FDA continues to warn about this risk (the most recent update was issued in April 2011), and the package insert of biologics still carries a black box warning about lymphoma.

Other adverse effects include worsening or triggering congestive heart failure, liver damage, and neurologic disorders. Long-term adverse effects have yet to be thoroughly studied and identified.

Preventing Side Effects

To reduce the risk of side effects, let your doctor know if you have:

  • chronic obstructive pulmonary disease (COPD)
  • congestive heart failure
  • diabetes
  • an infection or history of infections
  • tuberculosis or a positive skin test for tuberculosis
  • viral hepatitis

Also notify your doctor if you have been around an individual with chickenpox, shingles, or tuberculosis, or if you are scheduled to receive a vaccine or have surgery.

Drug Interactions

You should not take two or more biologics in combination. Studies show that when two or more biologics are taken at the same time, there is a substantially higher rate of serious adverse events than taking one of the drugs alone. Specific combinations that have been shown to have more adverse events include Kineret with Enbrel, and Orencia with Enbrel.

Biologics are often prescribed together with other medications, such as methotrexate, pain medications, or corticosteroids, and do not seem to interact with most drugs. But it’s important to note that there is little research on how the biologics interact with other drugs. Biologics, however, should never be taken together with other biologics, as this can increase the risk of severe adverse effects.

Because biologics affect your immune system, it is recommended that you should not be immunized with ‘live’ vaccines, such as the yellow fever vaccine, while you are on biologic therapy. In certain situations, however, a live vaccine may be necessary (for example, rubella immunization in women of childbearing age). You should discuss the possible risks and benefits of immunizations with your doctor. Other vaccines, such as flu vaccines (but not the nasal flu vaccine, FluMist, which contains live virus), are safe, and can be administered with biologic medications. But read the package insert of the biologic you are taking, and also discuss with your doctor any vaccines you plan to take.

Age, Race, and Gender Differences

People older than 65 and various ethnic groups have been underrepresented in most studies of biologics. Still, the existing evidence does not indicate that any biologic is more or less effective in older patients, people of any particular race or gender, or in patients who have other diseases.

The risk of biologics to unborn babies is unknown. Women of childbearing age should use contraception while on biologics. If you are planning to become pregnant, talk with your doctor about when to stop using contraception and biologics. The labeling of biologics advises these medications not be used by pregnant women unless necessary.

Are There Non-Drug Options?

Exercise can also help. Studies show that exercise programs improve the function of people with rheumatoid arthritis. These programs are typically recommended as a complement to, not a replacement for, medications.


Consumer ReportsUsing biologic drugs to treat rheumatoid arthritis. Comparing effectiveness, safety, side effects, and price. Published March 2013.