Treatments for Rheumatoid Arthritis: DMARDs
One of the most talked about treatments for rheumatoid arthritis (RA) involves the use of disease-modifying antirheumatic drugs or DMARDs. Studies show these medications can actually halt the underlying processes that cause rheumatoid arthritis by altering how the immune system functions.
In clinical trials, investigators have shown that patients have better clinical outcomes when the disease is diagnosed early and aggressive DMARD therapy is started immediately. The success with these drugs stems from the fact that they do more than just treat the symptoms of arthritis; DMARDs can also slow down or stop joint and tissue damage. It has even been suggested that a brief delay in the initiation of DMARD therapy can lead to more rapid joint destruction and loss of function over time.
However, it is important to note that DMARDs take time to work on the overall disease process, and their results may not be felt or seen for weeks or even months. For this reason, DMARDs typically are used with a nonsteroidal anti-inflammatory drug (NSAID) or a corticosteroid, which works on the inflammation, pain and swelling, and offers patients more immediate relief.
What are DMARDs?
Many types of drugs are classified as DMARDs. Some of these medications are traditionally used to treat other conditions, such as cancer or inflammatory bowel disease, or to reduce the risk of rejection of a transplanted organ. When they are used to treat rheumatoid arthritis, the doses are significantly lower and the risks of side effects tend to be considerably less. The various types of DMARDs include the following medications.
The most commonly used DMARD for rheumatoid arthritis is methotrexate. It is an immunosuppressive drug, taken by mouth or by injection that has proven highly effective at reducing the signs and symptoms of rheumatoid arthritis. Typically, it takes about four to six weeks for patients to experience a response to treatment. A trial of three to six months is usually suggested.
Methotrexate is usually well tolerated in low doses. The most common symptom is nausea, but the real concerns are hidden problems, such as severe toxicity to the liver and bone marrow. These potentially serious conditions can be detected and largely avoided with regular monitoring and blood testing. Doctors should also be on the lookout for a dry, nonproductive cough, which can be a sign of a rare lung toxicity. Methotrexate can impair fertility, decrease sperm count and cause menstrual dysfunction.
The drug works by suppressing the body's immune system, thereby reducing the inflammatory response. However, since immunity is suppressed, there is a greater likelihood for infection to develop. Any symptoms of infection should be reported to a physician. Moreover, patients with underlying immune deficiency diseases should not receive methotrexate.
Hydroxychloroquine sulfate (Plaquenil®) is another effective treatment for rheumatoid arthritis, particularly for mild to moderate disease. It is rapidly absorbed, relatively safe and well-tolerated. However, it also has side effects. In addition to nausea and stomach cramps, hydroxychloroquine sulfate has been known to cause serious eye conditions, including problems with the retina, visual disturbances, color blindness and loss of vision. Irreversible visual loss is also a concern. Fortunately, these problems can be detected and largely avoided with regular monitoring. This drug also affects the immune system, although doctors have not figured out exactly how it works and are uncertain whether it actually protects the joints from damage. It is given in pill form. Typically, it takes from 8 to 12 weeks for the body to respond to the treatment.
Organ Antirejection Drugs
Agents, such as azathioprine (Imuran®), cyclophosphamide (Cytoxan®) and cyclosporin A (Sandimmune®), are used to suppress the immune system in patients who have had kidney transplants. That same mechanism of action appears to decrease the inflammatory activity associated with rheumatoid arthritis.
This class of medications can lower white blood cell counts, which can increase a patient's risk of infection. This effect can be reversed when the dose is reduced or temporarily discontinued. These drugs can also induce nausea, vomiting and loss of appetite. Other side effects encountered less frequently include fatigue, hair loss and diarrhea.
On a more serious note, cytotoxic agents can cause liver toxicity, although studies indicate that this occurs in less than one percent of rheumatoid arthritis patients. All patients on cytotoxic agents must be monitored with regular testing of blood counts and liver function tests.
Sulfasalazine (Azulfidine En-tabs®) is a sulfa drug and anti-inflammatory agent used to treat inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. Like the other DMARDs, it has been shown to reduce the signs and symptoms of rheumatoid arthritis and to slow or halt the progressive damage that is often seen on X-rays. The side effects associated with this drug include hypersensitivity reactions due to sulfa allergy, mild gastrointestinal problems and occasionally, mild cytopenias, which is a reduction in the number of cells circulating in the blood.
Leflunomide (Arava®) is another medication used to treat rheumatoid arthritis. It suppresses the activity of immune cells that are responsible for inflammation. It is considered to be just as effective as methotrexate and represents a viable alternative to patients who are unable to use that drug. Studies show leflunomide can slow the progressive damage that is associated with rheumatoid arthritis. It can also be combined with methotrexate in patients who have no pre-existing liver disease, as long as the liver function tests are carefully monitored.
Other side effects of leflunomide include mild diarrhea, gastrointestinal upset and hair loss. It may cause high blood pressure, chest pain and abnormal heart beats. Women who are still in their child bearing years should take caution before using this drug.
A new class of medications, referred to as biologic response modifiers or "biologic agents" can specifically target parts of the immune system that are responsible for the inflammation and joint and tissue damage caused by rheumatoid arthritis. These medications are also DMARDs, because they slow the progression of the disease in a variety of ways.
Some block a specific inflammation factor, or cytokine, called the tumor necrosis factor. These drugs include adalimumab (Humira®), etanercept (Enbrel®) and infliximab (Remicade®). Others block an inflammation factor called interleukin-1. An example is anakinra (Kineret®). Newer biologic agents include abatacept (Orencia®) and rituximab (Rituxan®).
Biologic agents slow down rheumatoid arthritis in approximately 40 to 70 percent of people with the disease and can lead to remission. However, they do not cure the disease, as symptoms often return if the drug is stopped.
Because they target a specific component of the immune system, biologic agents have fewer side effects. However, they are only available by injection and are expensive. That is why they are generally reserved for patients whose rheumatoid arthritis does not respond to other treatments.