Rheumatoid arthritis is an autoimmune disorder associated with joint pain and numerous other manifestations that can affect areas of the body other than joints. The goal of therapy is to decrease inflammation and preserve the joints. According to Dr. J. Adam Rindfleisch of the University of Wisconsin, methotrexate treatment with newer biologic agents can lead to a 30 to 40 percent remission rate of the disease, but complete remission is uncommon.
Nonsteroidal Anti-Inflammatory Medications and Sulfasalazine
Nonsteroidal anti-inflammatory medications, or NSAIDs, work by blocking cyclooxygenase enzymes---Cox-1 and Cox-2---that are responsible for making prostaglandins. Prostaglandins are important for mediating inflammation in the body. NSAIDs are used to decrease both pain and inflammation of rheumatoid arthritis.
Commonly used NSAIDs are ibuprofen, brand names Motrin and Advil; naproxen, brand name Aleve; meloxicam, brand name Mobic; diclofenac, brand name Voltaren; indomethicin, brand name Indocin; and suldinac, brand name Clinoril. Celecoxib only blocks the Cox-2 enzyme. All these medications come in oral forms, and Voltaren also is prescribed as a topical gel treatment. Ibuprofen and naproxen are available as over-the-counter medications.
Methotrexate
Methotrexate is the first line disease-modifying anti-rheumatic drug (DMARD) for patients with rheumatoid arthritis that slow the progression of the disease. It has very good efficacy and a favorable side effect profile. Methotrexate works by inhibiting a pathway in folic acid metabolism. The end effect is an anti-inflammatory response. Methotrexate is given orally or as a subcutaneous injection. Side effects include liver damage, bone marrow suppression, oral ulcers, upset stomach and hair loss. Physicians monitor lab tests while patients are on methotrexate.
Sulfasalazine
Sulfasalazine, brand name Azulfidine, is a second line agent for rheumatoid arthritis. It is less effective than methotrexate, but it has been proven to reduce the signs and symptoms of rheumatoid arthritis and decrease X-ray findings. The effects may be due to folate depletion and blunting the immune response. It can be given along with methotrexate and hydroxychloroquine as "triple therapy." Side effects include allergic reactions to sulfa medication, gastrointestinal complaints and worsening anemia/hemolytic crisis if a patient has G6PD deficiency.
Antimalarials
Hydroxychloroquine, brand name Plaquenil, and chloroquine are antimalarial drugs that are safe for use in treating rheumatoid arthritis. The mechanism of action in treating rheumatoid arthritis is unknown. The end effect of antimalarials on rheumatoid arthritis is improvement in the symptoms and inflammation of the disease. The side effect profile includes the possibility of severe vision damage. Chloroquine is associated with more vision damage than hydroxychloroquine and is therefore not used as often.
Corticosteroids
Corticosteroids are good medications for short-term use to decrease inflammation and decrease the autoimmune response of rheumatoid arthritis. They can be administered orally, intravenously or by injection into the joint. Corticosteroids are naturally occurring hormones in the body that are produced by the adrenal glands. The potency of corticosteroids can result in a variety of unwanted side effects, including weight gain, stretch marks, high blood sugar, increased fat in the face referred to as "moon face," fat in the back of the neck called "buffalo hump," high blood pressure, cataracts and bone disease.
Leflunomide
Leflunomide, brand name Arava, is a pyrimidine synthesis inhibitor that may have effects on T-cells, a subclass of white blood cells. It works by suppressing the immune system, since rheumatoid arthritis is caused by damage from an overactive immune system. This medication is usually reserved for patients who fail to improve with methotrexate. It has a similar efficacy to methotrexate. Side effects include diarrhea, rash, hair loss and liver damage. Patients are monitored by lab tests while on this medication.
Immunomodulatory and Cytotoxic Agents
Immunomudulatory agents are newer therapies that are more directed at specific inflammatory markers and cell types. Tumor necrosis factor alpha, or TNF-alpha, is a pro-inflammatory marker produced by certain white blood cells that is found in large quantities in joints affected with rheumatoid arthritis. Medications like entanercept, or Enbrel, infliximab, or Remicade, and adalimumab, or Humira, all block TNF-alpha. All these medications carry a serious risk of infection, as they decrease the immune system response.
Abatacept, or Orencia, is a T-cell costimulatory blocker. Abatacept has the side effect of increased risk of infections.
Rituximab, or Rituxan, is a medication that works to deplete B-cells. B-cells are inflammatory cells that secrete antibodies and different inflammatory markers. It was originally marketed to treat non-Hodgkin's lymphoma, a condition of B-cells. Rituximab is typically reserved for rheumatoid arthritis patients that have failed anti-TNF-alpha blocking medications.
Anakinra, or Kineret, is a medication that works against interleukin-1, which is a pro-inflammatory marker found in high levels in rheumatoid arthritis. Anakinra is thought to be less effective than the anti-TNF-alpha blocking drugs and also carries a higher risk of infections while on the medication.
Cytotoxic agents include the following: azathioprine, brand name Imuran; cyclosporin A, brand names Sandimmune and Neoral; cyclophosphamide, or Cytoxan; and d-Penicillamine, brand names Cuprimine and Depen. These are highly toxic agents that are typically reserved for the life-threatening non-joint manifestations of rheumatoid arthritis or refractory joint disease.
References
- "Current Diagnosis and Medical Treatment"; Dr. Stephen McPhee, Dr. Maxine Papadakis; 2007
- American Family Physician: Diagnosis and Management of Rheumatoid Arthritis
