When the symptoms of psoriatic arthritis (PsA) are severe, doctors often turn to disease-modifying antirheumatic drugs (DMARDs) for treatment. These drugs alleviate the symptoms of psoriatic arthritis as well as slow down or stop joint and tissue damage and the progression of the disease.
DMARDs comprise several classes of medications. Traditionally, they are used to either reduce the body's risk of rejection of a transplanted organ or to treat conditions such as cancer or inflammatory bowel disease. When they are used to treat psoriatic arthritis, the doses are significantly lower and the risk of side effects tends to be considerably less.
The common denominator among all DMARDs is their ability to modify the underlying processes that cause inflammatory conditions such as psoriatic arthritis. They accomplish this feat by altering how the immune system functions. A description of the various types of DMARDs follows.
Chemotherapy Drugs
The most commonly used DMARD is methotrexate. Taken by mouth or injection, it is an immunosuppressive drug approved by the Food and Drug Administration (FDA) for the treatment of psoriasis, but it is also used widely and successfully for treating psoriatic arthritis. Methotrexate has proven effective at relieving the symptoms associated with psoriatic arthritis, and studies suggest it may help prevent joint destruction as well. It works by binding to an enzyme that is involved in the rapid growth of cells. Sometimes it is given in combination with other drugs to alleviate the signs and symptoms of psoriatic arthritis.
Methotexate is usually well tolerated in low doses. However, a number of side effects are associated with it, including the long term potential for liver damage. Regular blood tests are also needed to ensure that the body is tolerating the drug properly and to see if there are any negative effects on the bone marrow or the blood. Methotrexate can lower white blood cell counts, which can make a person more prone to infection.
Antimalaria Medications
Antimalaria drugs, such as hydroxychloroquine (Plaquenil®), are also effective at relieving pain, reducing joint inflammation and decreasing damage to the joints, skin and other organs in the body. Generally, it takes from 8 to 12 weeks for the body to respond.
Taken orally as a tablet, hydroxychloroquine affects the immune system. Doctors haven't figured out exactly how it works and are uncertain as to whether it protects the joints from damage. While hydroxychloroquine is generally well tolerated, it is not without side effects. In addition to nausea and stomach cramps, some reports have found that hydroxychloroquine may worsen psoriasis, because it makes the skin more sensitive. Antimalaria drugs have also been known to cause eye problems. Usually doctors turn to hydroxychloroquine when other treatments fail. It can be given along with steroid treatment to reduce the amount of steroid needed.
Health
Organ Antirejection Drugs
Cyclosporine (Neoral®, Sandimmune®) is an immunosuppressive drug that has been approved by the FDA for treating psoriasis. It may also provide fairly rapid relief from the symptoms of severe psoriatic arthritis. It is primarily known as a drug given to transplant recipients to prevent the body's rejection of a transplanted organ, and it works by preventing the actions of certain immune cells. Cyclosporine is associated with many side effects, including high blood pressure, high cholesterol, skin sensitivity and sometimes joint pain. Because it can damage the kidneys, it is usually recommended only for people who have not responded to other treatments.
Miscellaneous Drugs
Sulfasalazine (Azulfidine®) is a sulfa drug and anti-inflammatory agent used to treat inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. The active ingredients in this oral tablet are a sulfa antibiotic and salicylate, which is the main ingredient in aspirin.
Researchers aren't sure how this DMARD affects the immune system, but studies have shown it to be helpful to some people with psoriatic arthritis. Approximately one-third of patients with psoriatic arthritis respond within 4 to 8 weeks of this treatment. Sulfasalazine is generally well tolerated. Side effects may include skin rashes, headaches and nausea, and it may reduce the number of infection-fighting white cells in the body. Sulfasalazine may be used alone or in combination with other medications.
Acitretin (Soriatane®) is an oral, systemic retinoid that is approved by the FDA for severe skin psoriasis, but it may be effective for some patients with psoriatic arthritis as well. Again, it is not known exactly how the drug works for psoriatic arthritis, but doctors do know that retinoids affect how cells regulate their behavior. Oral retinoids carry the risk of birth defects in women of child-bearing potential, and the rare possibility of producing skeletal side effects with long-term use.
Leflunomide (Arava®) is an oral DMARD commonly used to treat rheumatoid arthritis. It has proven to be significantly effective in treating both the skin inflammation associated with psoriasis and the arthritis in patients with psoriatic arthritis. Leflunomide works by suppressing the action of the immune cells responsible for inflammation, but may cause high blood pressure, headaches, rash and diarrhea. It may also cause abnormal liver tests and should not be used by people with liver problems.
Biologic Agents
Biologics, or biological response modifiers, are recently developed DMARDs that specifically target the immune system and events in the body that cause psoriasis and psoriatic arthritis. They are given by self-injection or infusion in a physician's office and include etanercept (Enbrel®), adalimumab (Humira®), anakinra (Kineret®) and infliximab recombinant (Remicade®).
Biologics work by inhibiting a specific cell messenger known as tumor necrosis factor-alpha (TNF-alpha) that is involved in the inflammation process. In doing so, they have been shown to be highly effective at not only reducing the signs and symptoms of psoriatic arthritis, but also in slowing the progression of the disease. Because they are only available by injection and are expensive, they are reserved for people with psoriatic arthritis who do not respond to other treatments.
In addition to reactions at the site of the injection and side effects that include runny noses and headaches, TNF-alpha inhibitors have been associated with more serious problems. A recent analysis of several different studies found that treatment with these biologics has been linked to an increased risk for serious infection, such as pneumonia. There is also a potential risk for cancer associated with these drugs.
