There is no cure for rheumatoid arthritis, this almost goes without saying. However, there are a variety of medications which not only provide relief from pain and inflammation, but which also have the potential to put the disease into remission. And this should be the goal of every rheumatologist and every patient with rheumatoid arthritis: Remission, causing the rheumatoid arthritis to be inactive. Rheumatoid arthritis is inactive when a patient no longer experiences the hours of morning stiffness, and no longer experiences painful and swollen joints.
The following medications are used in the treatment of rheumatoid arthritis:
• NSAIDs. Non-steroidal anti-inflammatory drugs (NSAIDs) can relieve pain and reduce inflammation. Ibuprofen and naproxen can be purchased over the counter. More potent versions of these NSAIDs, in addition to others, are available only by prescription. These drugs can be helpful, but they do not have the ability to put rheumatoid arthritis into remission. Side effects of NSAIDs include ringing in the ears, easy bruising, stomach ulcers, heart problems, intestinal bleeding, and kidney and liver damage.
• Corticosteroids. Commonly known as “steroids,” these medications reduce inflammation and pain. Prednisone is the one most commonly prescribed to rheumatoid arthritis patients; however, doctors prefer to use steroids at a low dose, and for a short time, due to their side effects. The side effects include easy bruising, osteoporosis, weight gain, diabetes, cataracts and a round face.
• DMARDs. Disease-modifying antirheumatic drugs (DMARDs) have the ability to slow the actual disease process of rheumatoid arthritis, so that the inflammation and joint destruction is reduced, and the disease perhaps put into remission. DMARDs include methotrexate, leflunomide (Arava), hydroxychloroquine (Plaquenil), sulfasalazine (Azulfidine) and minocycline. Potential side effects include liver damage, low blood counts, diarrhea, nausea, hair loss and visual loss, depending on the particular drug.
• Immunosuppressants. These are medications which dampen the immune system, which is overactive in rheumatoid arthritis, as a patient’s own immune system attacks the lining of the joints, causing the classic symptoms of pain and inflammation. Examples of immunosuppressant drugs include azathioprine (Imuran), cyclosporine (Neoral), and cyclophosphamide (Cytoxan). Again, depending on the drug, side effects include infection, liver damage, kidney damage, low blood counts, nausea and diarrhea.
• Biologic DMARDs. These are medications that target specific inflammatory substances overproduced in rheumatoid arthritis, or particular inflammatory cells that are inappropriately activated in rheumatoid arthritis.
- TNF-alpha inhibitors. Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory substance produced in excess in rheumatoid arthritis. When this substance is inhibited, pain, inflammation and morning stiffness can be reduced, and often within a couple of weeks. It is not unusual for patients to go into remission with these drugs. Examples of TNF-alpha inhibitors include Enbrel, Remicade, Humira, Simponi and Cimzia. Potential side effects include irritation at the injection site, neurologic disease and increased risk of infection.
- Interleukin-1 inhibitor. Interleukin-1 (IL-1) is another one of the inflammatory substances, and it is inhibited by the medication Kineret.
- B-cell depleting drug. B-cells are activated in high-inflammatory states such as rheumatoid arthritis. Rituxan is a medication that depletes B-cells. Side effects include increased risk of infection, and possible neurologic disorder. It is indicated for patients who have not responded to TNF-alpha inhibitor therapy.
- T-cell costimulation inhibitor. Orencia is a medication which inhibits the activation of T-cells, another type of inflammatory cell in rheumatoid arthritis. An increased risk of infection appears to be the main side effect.
- Interleukin-6 inhibitor. Interleukin-6 (IL-6) is an inflammatory substance, targeted by the IL-6 inhibiting drug, Actemra. It is indicated for patients who have not responded to TNF-alpha inhibitor therapy. Potential side effects include an increased risk of infection, headache, liver damage, malignancy, high blood pressure, intestinal disorders and neurologic disorders.
There is no way to predict which patient will respond to what medication. The general approach among rheumatologists in the United States is to use a TNF-alpha inhibitor if a patient doesn’t respond to methotrexate. If TNF-alpha inhibition therapy is not effective, then it is reasonable to try either Rituxan, Orencia or Actemra next. The IL-1 inhibitor, Kineret, is thought to be less effective than the other biological DMARDs, and thus is usually reserved as a “last resort” by many who treat rheumatoid arthritis. The IL-6 inhibiting drug, Actemra, is the newest biologic on the market available to the general rheumatoid arthritis population. It remains to be seen how this drug is accepted by patients and doctors, compared to Rituxan and Orencia, which have been available as alternatives to the TNF-alpha inhibiting drugs for several years now.
Tailoring Treatment For the Patient
Sometimes, patients and their physicians are more concerned with the convenience of a particular medication, as long as it has a fairly decent chance of working. For example, there may be some rheumatoid arthritis patients who prefer Rituxan, because the administration of that drug involves two sessions of infusion into the vein, separated by two weeks; if another course is desired, that is generally given six months later, allowing the patient to not have to make as many trips to the intravenous infusion center compared to someone on, for example, Orencia or Remicade. On the other hand, a patient might not wish to deal with Rituxan, as the actual infusion sessions (that is, the time spent sitting in the chair, hooked up to an IV pole) are significantly longer compared to, for example, Orencia.
Of course, treatment must be tailored not just to patient preferences; the other health problems a patient may have must be given consideration when the choice of a drug is being considered. For example, Actemra has been shown to cause an elevation in blood pressure, and an elevation in the so-called “bad cholesterol”, the LDL. This combination of side effects is worrisome for any patient, but particularly the rheumatoid patient with a heart attack or stroke history. Clearly, a rheumatologist must know his or her patient; for, while the treatments for rheumatoid arthritis are becoming better and more varied all the time, ignorance of side effects coupled with ignorance of a patient’s medical history can result in more harm than good.