Medications For Rheumatoid Arthritis - Rheumatoid Arthritis: Arthritis

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Medications for rheumatoid arthritis

In the 1990s, the treatment of rheumatoid arthritis changed significantly, as researchers developed medications to treat this disease. In the past, doctors treated rheumatoid arthritis very conservatively. But evidence that joint damage starts early in the course of the disease has prompted physicians to treat it more aggressively from the beginning.

Given the complex nature of rheumatoid arthritis, and the fact that its progression varies from person to person, there are no easy answers when it comes to deciding on a treatment plan. In general, it is best to wait six to eight weeks to allow for a definitive diagnosis and to see how you respond to initial treatment before committing to long-term aggressive medical therapy. It is also important to remember that treatment should be tailored to the individual: Although some people with rheumatoid arthritis begin aggressive therapy within weeks of diagnosis, others may not need it right away.

Drugs for rheumatoid arthritis fall into several classes (see Appendix), and may be given in combination or sequentially. Although newly approved drugs tend to generate a lot of excitement, it's best to be cautious when using any new drug. The withdrawal of two COX-2 inhibitors from the market because of safety concerns shows dramatically that the true benefits and risks of any medication may not be known for years. Studies conducted to gain FDA approval for a drug may enroll no more than a few hundred or a few thousand people, who may be healthier than those who take the drug after it is approved. What's more, pre-approval studies are often limited in duration, while people taking the drugs for a disease like rheumatoid arthritis may take them for years. Uncommon side effects, interactions with other drugs, and long-term side effects only emerge in the general population in the years following approval. Unfortunately, there is no system in place to reliably identify these problems sooner. For all these reasons, make sure you understand and carefully weigh the risks and benefits before deciding to try a novel therapy.

NSAIDs and COX-2 inhibitors

To alleviate the pain and inflammation of rheumatoid arthritis, most doctors prescribe a nonsteroidal anti-inflammatory drug (NSAID), such as ibuprofen, or a COX-2 inhibitor, such as celecoxib (Celebrex).

Although anti-inflammatories can provide considerable benefit, they may also have a variety of side effects. If you are considering long-term use of any NSAID (including a COX-2 inhibitor), it is important to talk with your doctor about your personal health risks, particularly any gastrointestinal problems you may have. (For more on these medications, see "NSAIDs" and "COX-2 inhibitors.")

Although NSAIDs and COX-2 inhibitors can reduce pain and swelling, they have little if any effect on the disease process involved in rheumatoid arthritis. As a result, most people with rheumatoid arthritis need disease-modifying antirheumatic drugs (DMARDs) to control disease activity.

DMARDs

Disease-modifying antirheumatic drugs usually are used as first-line therapy in rheumatoid arthritis. They have the potential to slow the progression of rheumatoid arthritis by altering the function of the immune system. Because these medications can reduce or prevent joint damage and preserve joint function, they have become the standard of care for people with ongoing symptoms or joint damage.

DMARDs may be prescribed alone or in combination with drugs from other categories. Methotrexate (Folex, Rheumatrex, Trexall), when carefully prescribed, has an excellent safety profile, is highly effective, and is usually the first choice of therapy. It's also the drug against which all newer agents are judged. For example, leflunomide (Arava), a newer DMARD known as an immunomodulator, is proving to be as effective as methotrexate, and it has a different, but acceptable, safety profile. Like methotrexate, leflunomide can lead to liver toxicity. And it shouldn't be taken by anyone with compromised kidney function.

Other commonly prescribed DMARDs include hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine), although often these are chosen for mild disease, in combination with methotrexate or when methotrexate is not tolerated. Additional options include gold salts (Myochrysine), cyclosporine (Neoral), and penicillamine (Cuprimine, Depen), but these are used much less often because they appear to be less effective or less safe, or both.

Although DMARDs are often highly effective, their toxicity may extend to frequently proliferating cells that are vital to the body's renewal processes. For example, they may have damaging effects on the bone marrow, bladder, lung, liver, intestine, and reproductive organs. They also carry the risk of birth defects if taken by pregnant women. Anyone taking a DMARD is regularly monitored and may need to have frequent, complete blood cell counts, liver function tests, and urinalyses. The specific monitoring tests and frequency of testing vary depending on the drug taken.

One thing to keep in mind is that DMARDs are slow-acting drugs. Do not become discouraged and stop taking a DMARD before it has had a chance to work. Your doctor will probably advise you to take an NSAID, a corticosteroid, or both during the early weeks or months of treatment until the DMARD begins to take effect. Failure to respond to one DMARD does not mean you will also fail to respond to a different DMARD.

Biologic response modifiers

Biological response modifiers 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 be a primary instigator of joint inflammation (see Figure 9). Three anti-TNF agents are now available: adalimumab (Humira), etanercept (Enbrel), and infliximab (Remicade). About 60%–70% of people with rheumatoid arthritis respond well to anti-TNF agents.

Figure 9: How anti-TNF agents work When the immune system cells attack 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, the 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. Currently, infliximab, which received its initial FDA approval for treating Crohn's disease, is recommended for use only in combination with methotrexate. It is given intravenously at intervals of four to eight weeks. Adalimumab and etanercept are self-injected, like insulin. Etanercept must be injected once or twice a week, while adalimumab is injected every other week.

Anti-TNF therapy has been associated, though rarely, with long-term neurological side effects, including flare-ups in people with multiple sclerosis. Anti-TNF therapy also should not be taken by people who may have a latent tuberculosis infection or other bacterial infections. Infliximab should not be taken by anyone with congestive heart failure.

Other immune system modulators. In 2005, abatacept (Orencia) was approved for the treatment of rheumatoid arthritis. A co-stimulation modulator, abatacept keeps the immune system from attacking healthy tissues by interfering with T-cell activation. It appears to reduce the signs and symptoms of rheumatoid arthritis, slow structural damage, and improve physical function in people with moderate-to-severe disease who have not responded well to one or more DMARD or anti-TNF therapies. Abatacept is used alone or with DMARDs, but it should not be used with anti-TNF medications because the combination may lead to infections. It is given as an intravenous infusion every four weeks.

The more 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. It may also cause an allergic reaction in some people.

In 2006, the FDA approved the use of rituximab (Rituxan), a drug originally developed to treat non-Hodgkin's lymphoma, as a new treatment for rheumatoid arthritis. Rituximab, which is given as an intravenous infusion up to twice yearly, targets and helps to destroy B cells thought to become overactive when the immune system malfunctions in rheumatoid arthritis. Rituximab is supposed to be used in combination with methotrexate, and only in people with moderate or severe rheumatoid arthritis whose disease has not responded to one or more anti-TNF therapies.

The most common serious adverse event caused by rituximab is a condition known as lymphopenia (a reduction in the number of lymphocytes, a type of white blood cell). In rare cases, an initial infusion has caused severe skin reaction or death from kidney failure. Other serious reactions have included shortness of breath, lung congestion, abnormal heart rhythm, and low blood pressure. More common side effects during the first infusion include fever, shaking, chills, weakness, nausea, and headache.

A third drug, anakinra (Kineret), inhibits the actions of interleukin-1 (IL-1), an inflammatory chemical. The FDA approved anakinra in November 2001 for the treatment of moderate to severe rheumatoid arthritis in people who were treated with one or more DMARDs without success. Unfortunately, this drug has not lived up to its promise and is used infrequently.

Other medications

In some cases, corticosteroids or a device that filters the blood may provide further options for someone with rheumatoid arthritis.

Corticosteroids. Corticosteroids, such as prednisone, reduce the body's ability to generate an inflammatory reaction. But long-term use can actually damage the joints and cause other health problems such as osteoporosis, diabetes, increased susceptibility to infections, cataracts, and hypertension.

Today, corticosteroids are used very cautiously. They may be injected directly into a very inflamed joint or taken orally in low doses if other drugs fail to control inflammation. High doses are reserved for rare, life-threatening crises.

Prosorba column. This blood filtration device has been used since the 1990s to treat a rare blood disease; in 1999 it received FDA approval for use in treating rheumatoid arthritis. This device provides an option for people with moderate to severe rheumatoid arthritis who haven't seen improvement with drug therapy. In a process similar to kidney dialysis, blood is removed through an intravenous catheter attached to one of your arms and circulated through a machine that separates blood cells from plasma. The plasma passes through a column holding a protein that binds to and removes substances thought to cause joint pain and swelling (although these substances remain unidentified). The purified plasma is recombined with the blood cells and returned to the circulation through the other arm. It's effective only temporarily and is usually given once a week for 12 weeks.

Last updated:	September 05, 2008