The number of drugs used to treat rheumatoid arthritis has soared in the past 30 years, and their effectiveness has improved dramatically. Progress in this area is so rapid that many of the drugs considered optimal for rheumatoid arthritis today were not available 15 or 20 years ago.
Similarly, newer drugs or drug combinations will probably supplant today's treatments in the near future. At present, there are only a few basic approaches to drug treatment for rheumatoid arthritis:
Health-care providers begin treatment for rheumatoid arthritis with pain relievers and anti-inflammatory drugs. These drugs relieve pain and inflammation in the joints. They include oral pain relievers (analgesics), such as acetaminophen (Tylenol and others) or tramadol (Ultram), and nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, naproxen and many others.
NSAIDs. There are many possible side effects associated with NSAIDs. The most common side effect is gastrointestinal-tract irritation, including ulcers. Aspirin also may cause ringing in the ears or an increased rate of breathing. Additional side effects of NSAIDs include allergic reactions, easy bruising or bleeding, and liver or kidney injury.
Cyclooxygenase-2 (COX-2) inhibitors. COX-2 inhibitors are a newer type of NSAID. Currently, the only COX-2 inhibitor available in the U.S. is celecoxib (Celebrex), as rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the market after concerns arose regarding their cardiovascular safety. This type of drug may provide the same benefits as older NSAIDs but has a lower risk of ulcers. On the other hand, the higher costs and other potential side effects of COX-2 inhibitors may offset or partially offset this advantage.
In one study of celecoxib, the reduced risk of ulcers vanished in patients who also were taking low-dose aspirin for other conditions, such as heart disease or vascular problems.
Although pain relievers and NSAIDs can provide considerable benefit, people with rheumatoid arthritis usually require additional treatment. Pain relievers may reduce pain, and NSAIDs also may reduce swelling, but these drugs have little if any effect on the actual disease. That is, they can help you feel better, but inflammation may continue to damage the joints. Other drugs called disease modifying antirheumatic drugs (DMARDs) are often needed to control disease activity and, as a result, minimize or even halt, joint damage (see DMARDs below).
Topical pain relievers. Pain relievers also can be applied to the skin over the affected joint as an alternative to, or in addition to, oral pain relievers. Topical pain relievers include methyl salicylate, capsaicin cream and others. Capsaicin (Zostrix and others), a substance obtained from hot chilies, may cause mild skin irritation or a burning sensation when applied to the skin.
Corticosteroids, such as prednisone, are powerful drugs that promptly reduce inflammation. Improvement sometimes begins in less than a day. However, depending on the dose and duration of treatment, corticosteroids may have little lasting benefit and have a long list of concerning side effects, including:
- Easy bruising
- Bone thinning
- Weight gain
- Puffy face
- High blood pressure
Corticosteroids must be used under the strict supervision of your health-care provider. They are initially prescribed at the lowest effective dose to relieve acute (sudden, short-term) or severe symptoms, and then they are gradually reduced until you no longer need them, if possible. In the meantime, your health-care provider may initiate treatment with a DMARD, which slows disease activity but typically takes weeks or even months to take effect. It is important to reduce corticosteroid use gradually. Suddenly stopping this drug may cause serious problems, including low blood pressure or even shock.
When oral corticosteroids fail to control inflammation, corticosteroids may be injected directly into the affected joint. This procedure can temporarily relieve symptoms, but it is performed only rarely because of its associated risks and brief duration of action.
Disease-modifying antirheumatic drugs (DMARDs) can be an essential part of treatment. They have the potential to slow the progression of rheumatoid arthritis by altering the function of the immune system. The most commonly prescribed DMARDs include methotrexate, hydroxychloroquine, sulfasalazine and leflunomide. Newer, biologic DMARDs include abatacept, adalimumab, certolizumab, etanercept, golimumab, rituxan and toclizumab. Others — including gold, cyclosporine, penicillamine and minocycline — are used much less often because they appear to be less effective and/or less safe.
The older DMARDs, such as methotrexate, are slow-acting drugs that usually take weeks or months before the benefits become apparent. Do not become discouraged and stop taking a DMARD before it has had a chance to work (unless you have a side-effect or reaction; discuss any change in your medications with your doctor). Your health-care provider will probably advise you to take NSAIDs, a corticosteroid or both during the early weeks or months of treatment until the DMARD begins to work.
Failure to respond to one DMARD does not mean you also will fail to respond to a different DMARD. For example, even if you do not respond to methotrexate, you may respond well to sulfasalazine or etanercept. Researchers are still working to predict which patients will respond to which DMARD or combination of DMARDs, as well as the best time to initiate treatment.
Because of the risk of side effects, the use of any DMARD must be monitored by your health-care provider. Depending on the drug used, side effects may include vision problems, dermatitis (skin inflammation) and skin rashes, liver injury, nausea, diarrhea and abnormal blood counts. Keep in mind that even if one DMARD causes an unacceptable side effect, it does not mean you will have the same reaction to all DMARDs.
Newer, injectalbe DMARDs are often called “biologics” because their mode of action is to counter biologically active substances that cause inflammation in joints. These drugs can be highly beneficial, but most arthritis specialists begin treatment with other drugs because newer DMARDs are expensive and have uncertain long-term effects and/or potential side effects. Such drugs may be used earlier and more frequently if the price falls and if studies show them to be safe and effective in early stages of the disease.
For example, a year or two after infliximab was approved, researchers found that tuberculosis was more common than expected among patients taking this drug. Furthermore, researchers have noted a higher rate of death among infliximab-treated patients who had congestive heart failure. These findings have led to new recommendations about how patients should be screened before initiating DMARD treatment.
Among the newest treatments approved by the U.S. Food and Drug Administration for rheumatoid arthritis is tofacitinib. This drug is different from the other newer drugs in that it is an oral medication and it is not considered a biologic; it inhibits an enzyme in inflammatory cells, interrupting the signal between cytokines outside the cell and the nucleus inside the cell. This interrupted signal leads to reduced inflammation. Its precise role in the treatment of rheumatoid arthritis is uncertain but it may be helpful for rheumatoid arthritis that has not responded to other treatments.