Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
Disease-modifying antirheumatic drugs (DMARDs): This group of drugs includes a wide variety of agents that work in many different ways. What they all have in common is that they interfere in the immune processes that promote inflammation in rheumatoid arthritis. DMARDs can actually stop or slow the progression of rheumatoid arthritis. They can also suppress the ability of the immune system to fight infections. Anyone taking one of these drugs must be very vigilant to watch for early signs of infection, such as fever, cough, or sore throat. Early treatment of infections can prevent more serious problems.
Methotrexate (Rheumatrex, Folex PFS): We do not know exactly how this drug works in the treatment of inflammatory reactions. It relieves symptoms of inflammation such as pain, swelling, and stiffness. People taking methotrexate have to have regular blood tests to measure whether the drug is having any adverse effects on the liver, kidneys, or blood cells. This drug is not suitable for some people with liver problems or women who are or may become pregnant.
Sulfasalazine (Azulfidine): This drug decreases inflammatory responses by an effect similar to that of aspirin or NSAIDs. People taking sulfasalazine must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.
Leflunomide (Arava): This drug interferes with cells of the immune system and reduces inflammation. It reduces symptoms and may even slow the progression of rheumatoid arthritis. People taking leflunomide must have regular blood tests to measure whether the drug is having any adverse effects on the liver or blood cells. This agent is not suitable for some people with liver or kidney problems or women who are or may become pregnant.
Gold salts (aurothiomalate, auranofin [Ridaura]): These compounds contain very tiny amounts of the metal gold. We do not know why they stop inflammation. Apparently, the gold infiltrates into immune cells and interferes with their activities. People taking gold must have regular blood and urine tests to measure whether the drug is having any adverse effects on blood cells and the kidney.
D-penicillamine: This agent combines with metals in the bloodstream and cells and removes them from the body. This suppresses certain actions of the immune system that promote rheumatoid arthritis. People taking D-penicillamine must have regular blood and urine tests to measure whether the drug is having any adverse effects on blood cells and the kidney.
Hydroxychloroquine (Plaquenil): This drug was first used against the tropical parasite malaria. It inhibits certain cells that are necessary for the immune response that causes rheumatoid arthritis. People taking hydroxychloroquine must have eye examinations at least yearly to determine whether the drug is having any adverse effects on the retina.
Azathioprine (Imuran): This drug stops the production of cells that are part of the immune response associated with rheumatoid arthritis. Unfortunately, it also stops production of some other types of cells and thus can have serious side effects. It strongly suppresses the entire immune system and thus leaves the person vulnerable to infections and other problems. It is used only in severe cases of rheumatoid arthritis that have not gotten better with other DMARDs. People taking azathioprine must have regular blood tests to measure whether
or not the drug is having any adverse effects on blood cells. It is not used for women who are or may become pregnant.
Cyclosporine (Neoral): This drug was developed for use in people undergoing organ transplantation or bone marrow transplantation. These people must have their immune system suppressed to prevent rejection of the transplant. Cyclosporine blocks an important immune cell and interferes with the immune response in several other ways. People taking cyclosporine must have regular blood tests and blood pressure checks to measure whether the drug is having any adverse effects on blood cells and blood pressure.
It is not used for women who are or may become pregnant.
Biologic response modifiers: These agents act like substances produced normally in the body and block other natural substances that are part of the immune response. They block the process that leads to inflammation and damage of the joints. These are targeted treatments that are directed at specific sites in the immune system that are involved in the rheumatoid process.
Etanercept (Enbrel): This agent blocks the action of tumornecrosis factor, which in turn decreases inflammatory and immune responses. It is given by subcutaneous injection twice weekly. People taking etanercept must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.
Infliximab (Remicade): This antibody blocks the action of tumor necrosis factor. It is often used in combination with methotrexate in people whose rheumatoid arthritis does not respond to methotrexate alone. It is given by intravenous infusion every
six to eight weeks. People taking infliximab must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.
Adalimumab (Humira): This is another blocker of tumor necrosis factor. It reduces inflammation and slows or stops worsening of joint damage in fairly severe rheumatoid arthritis. It is given by subcutaneous injection every
two weeks. People taking adalimumab must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.
Certolizumab (Cimzia): This is another blocker of tumor necrosis factor. It reduces inflammation and slows or stops worsening of joint damage in fairly severe rheumatoid arthritis. It is given by subcutaneous injection every four weeks. People taking certolizumab must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.
Golimumab (Simponi): This is another blocker of tumor necrosis factor. It reduces inflammation and slows or stops worsening of joint damage in fairly severe rheumatoid arthritis. It is given by subcutaneous injection every four weeks. People taking golimumab must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.
Anakinra (Kineret): This agent blocks the action of interleukin-1, which is partly responsible for the inflammation of rheumatoid arthritis. This in turn blocks inflammation and pain in rheumatoid arthritis. This agent is usually reserved for people whose rheumatoid arthritis has not improved with DMARDs. It is given by subcutaneous injection daily. People taking anakinra must have regular blood tests to measure whether the drug is having any adverse effects on blood cells.
Abatacept (Orencia): This agent inhibits T-lymphocytes that contribute to the inflammation and pain associated with rheumatoid arthritis. This drug is reserved for individuals who do not respond to DMARDs, methotrexate, or TNF blockers. It is administered by intravenous infusion. Abatacept may increase the risk of serious infections.
Rituximab (Rituxan): Given by intravenous infusion over four to five hours, twice,
two weeks apart, every four to 10 months, this biologic response modifier decreases the number of B-cells, a type of immune cell that plays an
integral role in causing rheumatoid inflammation and damage. Rituximab may increase the risk of serious infections.
Tocilizumab (Actemra): The agent blocks the chemical messenger interleukin-6 (IL-6) that plays a role in activating the immune system that is responsible for rheumatoid arthritis. Tocilizumab is given intravenously once a month. Regular blood testing is required to monitor for potential side effects on blood cells, liver, and cholesterol levels.
Glucocorticoids: These very potent agents rapidly block inflammation and other immune responses. They are often called steroids. These agents all work in the same way; they differ only in their potency and in the form in which they are given. Steroids may be given as pills, intravenously, or as injections into a muscle or directly into a joint. In high doses, they can cause many serious side effects and are
therefore given only for the shortest possible periods and under strictly controlled circumstances. These drugs should never be stopped abruptly.
Nonsteroidal anti-inflammatory drugs (NSAIDs): These drugs reduce swelling and pain but do not stop joint damage and alone are not sufficient to treat rheumatoid arthritis. These drugs work by blocking an enzyme called cyclo-oxygenase (COX) that promotes inflammation. There are at least
two forms of the enzyme: COX-1 and COX-2. Some people with a history of stomach ulcers or liver problems should not take these drugs. This group includes aspirin, although aspirin is rarely used in rheumatoid arthritis because it is not as safe as other agents.
COX-2 inhibitors: These agents block only the COX-2 enzyme and are often referred to as selective NSAIDs. They have fewer side effects than the other NSAIDs while still reducing inflammation. Only celecoxib (Celebrex) currently remains on the U.S. market.
On Sept. 30, 2004, Merck & Co, Inc., announced a voluntary withdrawal of the COX-2 inhibitor rofecoxib (Vioxx) from the U.S. and worldwide market because of its association with an increased rate of cardiovascular events (including heart attacks and strokes) compared to that of placebo. A major U.S. Food and Drug Administration (FDA) study of rofecoxib found an apparent
threefold increase in the risk of sudden cardiac death or heart attack among patients who had taken higher doses of the drug compared to the risk of patients who had not recently received similar medication. The report showed that even patients taking the standard starting dose of 12.5 mg or 25 mg of rofecoxib had a 50% greater chance of heart attack or sudden cardiac death than patients on any dose of celecoxib (Celebrex). The large-scale study was conducted after analyzing the medical records of 1.4 million people insured by Kaiser Permanente in Oakland, Calif., between 1999-2001. Note: The study had inherent limitations in that it
was observational, rather than randomized and controlled.
On Apr. 7, 2005, valdecoxib (Bextra, by Pfizer, Inc.) was voluntarily withdrawn from the U.S. market, pending further discussion with the FDA. The association of valdecoxib with potentially life-threatening risks, including myocardial infarction, stroke, and serious skin reactions, initiated an investigation to determine whether the benefits of the drug outweighed the risks. The serious skin reactions are most likely to occur in the first
two weeks of treatment, but they can occur any time during therapy. Other COX-2 inhibitors and traditional NSAIDs (for
example, naproxen [Aleve, Naprosyn], ibuprofen [Motrin]) also have a risk for these rare, serious skin reactions, but the reported rate of the reaction appears to be greater for valdecoxib. Newer data regarding risks in individuals who take valdecoxib following heart bypass surgery showed an increased risk of heart attack, stroke, deep vein thrombosis (blood clots in the leg), and pulmonary embolism (blood clots in the lungs).
Nonselective NSAIDs: These drugs block both COX-1 and COX-2. They include ibuprofen (Motrin, Advil, etc.), ketoprofen (Oruvail), naproxen (Naprosyn), piroxicam (Feldene), and diclofenac (Voltaren, Cataflam).
Analgesics: These agents reduce pain but do not affect swelling or joint destruction.
Acetaminophen (Tylenol, Feverall, Tempra): This drug is often used by people who cannot take NSAIDs because of hypersensitivity, ulcers, liver problems, or interactions with other drugs.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown cause that primarily affects the peripheral joints in a symmetric pattern.
