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Anti-rheumatic drugs
The current trend is to start using potent anti-rheumatic drugs right away if basic anti-inflammatories fail to control symptoms. These potent drugs are usually referred to as disease-modifying anti-rheumatic drugs (DMARDs) but are also called SAARDs (slow-acting anti-rheumatic drugs).
Antimalarials. The most commonly used antimalarial is hydroxychloroquine (Plaquenil). Between 30 percent and 40 percent of people with RA respond to this drug, but improvement does not begin for three to six months. The advantage of this drug is its low incidence of side effects. The most serious risk-- vision loss due to damage to the retina--is rare at low dosages, but regular eye exams are required during long-term treatment. Other side effects are gastrointestinal problems and, in rare instances, inflammation of the nervous system and skeletal and heart muscles.
Azathioprine. Azathioprine (Imuran) is an antimetabolite (a substance that blocks a normal metabolic process) and is most commonly employed as an immunosuppressant to prevent rejection of transplanted kidneys and hearts. Because it can cause dangerous suppression of the immune system that may lead to serious infection, it is used only when severe symptoms fail to respond to safer drugs. Digestive side effects, such as loss of appetite, nausea, or, rarely, vomiting, may develop.
Corticosteroids. The corticosteroid drug prednisone (Deltasone, Meticorten, Prednisone Intensol, Sterapred) usually produces rapid and dramatic symptomatic improvement by reducing inflammation and suppressing the immune system. As a result, physicians and patients alike have been tempted to continue steroid use for long periods, despite many serious side effects including stomach ulcers, diabetes, high blood pressure, muscle wasting, cataracts, increased susceptibility to infections, and psychiatric disturbances. Osteoporosis is also an important side effect of steroid use, occurring in as many as 50 percent of patients. A baseline bone scan should be done before beginning therapy for comparison purposes. Follow-up scans every six months to one year afterward can be used to monitor changes in bone density. Also, people taking steroids should get 1,500 mg of calcium and 400 to 800 IU of vitamin D daily.
Low-dose hormone replacement therapy can be used to maintain or improve bone density in postmenopausal women, but this treatment has been associated with a small increase in the risk of breast cancer and cardiovascular disease. For this reason, an osteoporosis treatment such as alendronate (Fosamax), risedronate (Actonel), or calcitonin (Calcimar, Miacalcin) may be a better choice.
When corticosteroids are discontinued after being used at high doses or for a long time, the dose must be reduced very slowly to help prevent a flare of arthritis.
Cyclophosphamide. The anticancer drug cyclophosphamide (Cytoxan, Neosar) has proved beneficial in studies of people with RA who have not responded adequately to any other therapeutic measure. Serious inflammation of the bladder (hemorrhagic cystitis) is a possible side effect. Also, cyclophosphamide can cause fetal damage if administered to a pregnant woman, an important concern because many RA sufferers are women of childbearing age.
Cyclosporine. The drug cyclosporine (Neoral, Sandimmune) is an immunosuppressant that is most commonly used to prevent rejection of transplanted organs. It relieves symptoms of RA by inhibiting the growth and action of immune system cells, including those that cause joint pain and swelling. Because it is highly toxic and can cause high blood pressure and damage to the kidneys, it should be administered in low doses over a period of time, and patients must be monitored closely.
Gold salts. Therapy with gold salts (chrysotherapy), which is used in people who do not respond to NSAIDs and are unable to take methotrexate (see below), is beneficial about 60 percent of the time. Gold salts appear to act by suppressing synovial inflammation during active RA. The benefits of treatment are not apparent for about three to six months. Gold is administered either by intramuscular injections or by oral dosages--though injected gold is more effective overall than oral treatment.
Side effects, which occur in about a third of people receiving gold injections, include inflammation of the skin and mucous membranes of the mouth, diarrhea, protein in the urine, and a drop in white blood cell levels. Even those who have tolerated gold injections for several years need to watch for adverse reactions, including dizziness, nausea, and pain within an hour of the injection. Regular blood tests are necessary to monitor side effects.
Methotrexate. Methotrexate (Rheumatrex), which acts as a mild immunosuppressant, was first used to treat some forms of cancer. It is now recognized as the drug of choice for people with severe RA that does not respond to NSAIDs. It often leads to improvement within a month.
The most common side effects are irritation of the stomach and inflammation of the mucous membranes of the mouth. Rarely, the drug produces an extremely dangerous toxic reaction that may include lung inflammation, bone marrow suppression, and severe liver damage.
Because methotrexate may harm the liver, experts recommend periodic blood tests to monitor liver function. A biopsy should be performed only if blood tests indicate liver damage.
Based on recent studies, low-dose folic acid supplements are recommended as an inexpensive way to reduce methotrexate side effects. The supplements appear to reduce the liver toxicity of the drug.
Research on the use of methotrexate to treat RA may in fact result in a major change in the approach rheumatologists take in starting drug therapy. An analysis of results from 11 clinical trials indicates that, contrary to current practice, RA should be treated aggressively in the initial stages of the disease. The analysis found that methotrexate produced major improvements in 44percent of patients during the first year of the disease. The beneficial effect dropped dramatically after five years; just 29percent of people who had RA for more than five years were helped by methotrexate. If these findings are borne out by further research, potent drugs may be prescribed early in the course of the disease to gain better control of symptoms. Additional studies have shown that methotrexate is more effective when combined with other drugs, such as cyclosporine, leflunomide (Arava), etanercept (Enbrel), infliximab (Remicade), or adalimumab (Humira).
Minocycline. Minocycline is a tetracycline antibiotic that has been studied for use in RA. It is unclear how it might work but is believed to reduce inflammation.
Penicillamine. Penicillamine (Cuprimine, Depen) has proved effective--particularly in studies carried out in the United Kingdom --in people who are unresponsive to all other measures. Its use is limited, however, by adverse reactions that include fever, rash, mouth ulcers, loss of taste, protein in the urine, and low blood levels of white blood cells and platelets.
Sulfasalazine. Sulfasalazine (Azulfidine EN-tabs) appears to suppress the immune system response that is activated in RA and also acts as an anti-inflammatory agent. The drug generally does not take effect for at least four weeks. Because of adverse effects--which include skin rash, headache, nausea, vomiting, stomach problems, loss of appetite, and decreased sperm count--patients should be monitored closely for the first three months of therapy.
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