Rheumatoid Arthritis: How to Treat
What is rheumatoid arthritis?
Arthritis is a general term that describes inflammation in joints. Rheumatoid arthritis is a type of chronic (ongoing) arthritis (resulting in pain and swelling) that occurs generally in joints symmetrically (on both sides of the body, such as hands, wrists and knees). This involvement of several joints helps distinguish rheumatoid arthritis from other types of arthritis.
In addition to affecting the joints, rheumatoid arthritis may occasionally affect the skin, eyes, lungs, heart, blood, nerves or kidneys.
What are the goals of treating rheumatoid arthritis?
The most important goal of treating rheumatoid arthritis is to reduce joint pain and swelling and to maintain and/or improve joint function.
The long-term goal of treatment is to slow or stop the disease process, particularly joint damage, which can be seen on X-rays. Once joint inflammation is controlled, pain will be reduced.
Normal joint (left) and joint affected by rheumatoid arthritis
In the past, many doctors did not believe that drugs for rheumatoid arthritis changed the likelihood of eventual disability from the disease. Therefore, drugs with the fewest side effects were prescribed to decrease pain. Stronger drugs were avoided because of doctors' concerns about dangerous side effects.
Now, however, doctors know that early treatment with certain drugs can improve the long-term outcome for most rheumatoid arthritis patients. Numerous drugs that have been shown to be effective are being used soon after the patient is diagnosed. Combinations of drugs are proving to be more effective than a single drug therapy and, in recent studies, have been found to be just as safe as single-drug treatment.
What drugs are used to treat rheumatoid arthritis?
The drugs used to treat rheumatoid arthritis can be divided into three groups:
- Drugs that decrease pain and inflammation. These products include non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin®), naproxen (Aleve®), and other similar products. Another type of drug – the COX-2 inhibitor – also falls into this drug category, providing relief of the signs and symptoms of rheumatoid arthritis. Celecoxib (Celebrex®), one COX-2 inhibitor, is available and used in the United States. The COX- 2 inhibitors were designed to have fewer bleeding side effects on the stomach.
- Disease-modifying antirheumatic drugs (DMARDs). Unlike other NSAIDs, DMARDs can actually slow the disease process by modifying the immune system. Older DMARDs include methotrexate (Trexall®), gold salts, penicillamine (Cuprimine®), hydroxychloroquine (Plaquenil®), sulfasalazine (Azulfidine®), cyclosporine (Sandimmune®), cyclophosphamide (Cytoxan®) and leflunomide (Arava®). Currently, methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine are the most commonly used. (Cyclosporine, cyclophosphamide, gold salts, and penicillamine are not used any more.) Many of these drugs were first used to treat other medical conditions – such as malaria, transplant rejection, cancer, psoriasis and inflammatory bowel disease – but have now also found a role in treating rheumatoid arthritis.
DMARDs are used both alone and in combination. Methotrexate, for example, is often used as a major part of a combination drug regimen, which includes low doses of corticosteroids (such as prednisone or cortisone) as well as other drugs. Treatment to improve symptoms may require four to six weeks of methotrexate, one to two months of sulfasalazine, and two to three months of hydroxycholoroquine.
- Biologics. Beyond these more "traditional" DMARDs, newer medications have been approved. Currently, there are seven different classes of medications and, in some cases, there are different kinds in each class. (Some of them, such as the class anti-TNFs, have been used since 2000.) Collectively, these DMARDs are known by another name – biologic agents (or biologic response agents). Compared with the traditional DMARDs, these products target the molecules that cause inflammation in rheumatoid arthritis.
Inflammatory cells in the joints are involved in the development of rheumatoid arthritis itself. The biologic agents cut down the inflammatory process that ultimately causes the joint damage seen in rheumatoid arthritis. The older DMARDs work one step further out than the biologics; they work by modifying the body's own immune response to the inflammation. By attacking the cells at a more specific level of the inflammation itself, biologics are considered to be more effective and more specifically targeted. The biologic agents include etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), anakinra (Kinaret®), abatacept (Orencia®), rituximab (Rituxan®), certolizumab pegol (Cimzia®), golimumab (Symponi®), tocilizumab (Actemra®) and tofacitinib (Xeljanj®). Some of the biologics are used in combination with the traditional DMARDs, especially with methotrexate.
How well do the drugs work? Are they dangerous?
All the drugs used to treat rheumatoid arthritis have been tested and have been proven useful in patients who have the disease. However, they all work on a different aspect of the inflammatory process seen in rheumatoid arthritis and their use – as well as their side effects -- depends on the current disease status of each patient and any associated medical problems that a patient may have. The effectiveness and the risks of drugs are considered when your rheumatologist plans your treatment.
If a drug is very effective in treating an illness but causes a lot of side effects, it is not an ideal treatment for long-term use. For example, high doses (15 to 20 mg or more per day) of corticosteroids can make people with rheumatoid arthritis feel dramatically better. However, high doses of corticosteroids may cause serious side effects when taken over many months or years. Steroids have many possible side effects, including weight gain, worsening diabetes, promotion of cataracts in the eyes, thinning of bones (osteopenia and osteoporosis), and an increased risk of infection. Thus, when steroids are used, the goal is to use the lowest possible dose for the shortest period of time.
- NSAIDs. All of the NSAIDs are similarly effective, making it difficult for doctors to strongly recommend one over the other. These drugs can cause irritation of the stomach and kidney damage as side effects. Therefore, their use in people with severe stomach and kidney problems should be closely supervised by doctors.
- COX-2 anti-inflammatory agents. These drugs work by restraining a certain enzyme in the body (cyclooxygenase 2, i.e., COX-2), which in turn reduces the amount of bad prostaglandins. Thus, inflammation is reduced, leaving the other good prostaglandins that protect the stomach and kidneys alone. COX-2 inhibitors are sometimes used in patients who cannot take ordinary NSAIDs, such as those who are concerned about stomach ulcers and gastric irritation.
- DMARDs. The "traditional" DMARDs work by a different mechanism than NSAIDs and work well. For example, methotrexate is widely used and most effective in providing benefits for people with rheumatoid arthritis. It is often referred to as the "cornerstone of therapy" and is used alone or in combination with other drugs. However, traditional DMARDs act slowly after starting the drug for several weeks.
- Biologic agents. Biologic agents are more specifically targeted at the inflammatory process seen in rheumatoid arthritis. This leads to another big advantage of using the biologics: they tend to be better tolerated and sometimes able to work faster than traditional DMARDs. However, all of the biologic agents can have side effects and will need to be used under the supervision of your rheumatologist.
(Note: DMARDs and biologic agents interfere with the immune system's ability to fight infection and should not be used in people with serious infections.)
- Anti-TNF agents: Anti-TNF agents such as infliximab, etanercept, adalimumab, certolizumab and golimumab are not recommended for people who have lymphoma or who have been treated for lymphoma in the past; people with rheumatoid arthritis, especially those with severe disease, have an increased risk of lymphoma regardless of what treatment is used. Anti-TNF agents have been associated with a further increase in the risk of lymphoma in some studies but not others; more research is needed to define this risk.
Testing for tuberculosis (TB) is necessary before starting anti-TNF therapy. People who have evidence of an earlierTB infection should be treated because there is an increased risk of developing active TB while receiving anti-TNF therapy.
How will my doctor choose drugs that are right for me?
Your doctor will work with you to develop a treatment program. The drugs your doctor prescribes will match the seriousness of your condition.
Your doctor will combine the results of your medical history, physical exam, X-rays and blood tests to create your treatment program. The doctor will also consider your age, sex, physical activity, other medications you are taking and any other medical conditions you may have.
It is important to meet with your doctor regularly so that he or she can closely monitor you for any side effects and change your treatment, if necessary. Your doctor may periodically order blood tests or other tests to determine the effectiveness of your treatment and any side effects.