Rheumatoid arthritis: prescription medications
Whatever form of arthritis you may have, medications are likely to be an important part of your treatment plan. It is important that you understand your medication options, so that you can get the most out of the treatments that your doctor prescribes.
The course of rheumatoid arthritis (RA) is such that the inflammation created when the disease is active results in damage to the joints. This can be seen as bone erosions. The main aim of treating RA is to give medications which will suppress the inflammation. Effective treatment also aims to prevent joint destruction and the disability which results from this.
Disease-Modifying Anti-Rheumatic Drugs (DMARDs)
Disease-Modifying Anti-Rheumatic Drugs (DMARDs) are sometimes also known as slow-acting anti-rheumatic drugs (SAARDs). They work by suppressing inflammation. Many DMARDs also retard the development of joint erosions, although the exact mechanism for this is not well understood. Their effectiveness is often judged by their ability to slow the progression of erosions as measured on X-rays.
It is important that treatment with DMARDs is started as soon as active RA is diagnosed, in order to help prevent joint deformity and disability. Once a sufficient dose is reached it takes 6-8 weeks to achieve beneficial effects. Because there are a number of potential side effects associated with taking DMARDs, the treatment should be closely monitored. Regular blood and urine tests are often done to identify potential problems early on.
Here are some of the DMARDs that are used in the treatment of RA.
- Methotrexate (e.g. Ledertrexate, Methoblastin) is generally used in moderate to severe RA. Methotrexate can be administered either orally or intramuscularly, and supplements of folic acid are recommended to alleviate side effects such as nausea and mouth ulcers. It is potentially toxic to the liver. Methotrexate is considered to be the gold standard DMARD against which other agents are compared.
- Sulfasalazine (e.g. Pyralin EN, Salazopyrin EN), is used to treat mild RA because it is less potent than some other DMARDs and has fewer adverse effects. It can still, however, cause nausea, dyspepsia, diarrhoea, rash and headaches, but these are less frequent once the maintenance dose is achieved. More seriously, it occasionally causes severe anaemia.
- Leflunomide (e.g. Arava), is used to treat severe active RA that does not respond to classical DMARDs such as methotrexate. Leflunomide is as effective as methotrexate in the treatment of RA.
- Intramuscular gold injections of sodium aurothiomalate (e.g. Myocrisin), have a significant clinical benefit in the treatment of patients with RA. These are not used as commonly nowadays as some of the other treatment options because of unfavourable side effects such as mouth ulcers, rash, thrombocytopenia (a deficiency of platelets — cells that are involved in blood clotting), and proteinuria (protein in the urine).
- Oral gold such as auranofin (e.g. Ridaura) is used less frequently now, largely because of low efficacy. Diarrhoea is a common side effect.
- Antimalarials such as hydroxychloroquine sulfate (e.g. Plaquenil) are used in the treatment of mild rheumatoid arthritis. Their overall effects are mild, but they are less toxic than some of the other treatments. Plaquenil is often used in combination with other DMARDs.
- Penicillamine (e.g. D-Penamine) is used in the treatment of moderate to severe RA. It appears to be as effective as other DMARDs, but with a higher toxicity. It is seldom used nowadays.
- Cyclosporin (e.g. Neoral and Sandimmun), originally developed to prevent organ rejection in transplant patients, is used either on its own or in combination with other anti-arthritic drugs. Cyclosporin shows clinical benefit in short-term treatment (up to one year) of people with progressive RA. People taking cyclosporin have to be carefully monitored for adverse effects, which are common.
- Azathioprine (e.g. Imuran) is used to treat only severe active RA that is unresponsive to other DMARDs. Because of high toxicity it is now seldom used.
Trials of combination therapy have shown positive results. A combination of methotrexate, hydroxychloroquine and sulfasalazine is more effective than methotrexate alone. A combination of cyclosporin with methotrexate appears to be more effective than methotrexate alone.
Non-steroidal anti-inflammatory drugs (NSAIDs)
Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed as pain killers. They also reduce inflammation in the treatment of inflammatory forms of arthritis, such as RA. They do not stop the disease from progressing but may relieve symptoms. Some, such as ibuprofen (e.g. Nurofen or Tri-Profen) and naproxen (e.g. Naprogesic) are available over the counter, while others (such as diclofenac, piroxicam, sulindac and indomethacin) are available as prescription medicines only.
The use of NSAIDs is often limited because they increase the risk of upper gastrointestinal problems, such as gastric ulcer. They are not suitable for use by people who have had a peptic ulcer or gastrointestinal bleeding.
COX-2 specific inhibitors
The coxibs (e.g. celecoxib — brand name Celebrex) are also non-steroidal anti-inflammatory agents. However, in addition to having a similar effect on reducing inflammation and relieving pain they are much gentler on the stomach. Studies have shown that the coxibs have lower rates of gastric ulcer associated with them than the conventional, older NSAIDs.
However, coxibs may be associated with an increased risk of cardiovascular events, such as heart attack and stroke, when taken in high doses. People who have an increased risk of heart attack or stroke should not take these medications. You can discuss the risks and benefits of treatment with coxibs with your doctor, who will be able to tell you whether or not they are suitable for you.
Corticosteroids
Corticosteroids, sometimes known as glucocorticoids, such as prednisone and prednisolone, are powerful agents that work by reducing inflammation and suppressing the immune system. Corticosteroids are used in the treatment of RA, both as tablets and as injections into the joint.
Prednisolone is sometimes used in moderate to severe RA where NSAIDs and DMARDs are not controlling the disease. Oral corticosteroids (those taken by mouth) are usually used at the lowest effective dose to minimise adverse effects such as weight gain, hypertension (high blood pressure) and osteoporosis.
Alternatively, corticosteroids may be injected into the joints if the arthritis is not being controlled by oral therapy, but this should be limited to 3 to 4 injections a year. Joints commonly injected are fingers, toes, knees and shoulders. Corticosteroids are also sometimes injected into the muscles.
Biologic agents
Recently, another category of arthritis treatments called tumour necrosis factor (TNF) inhibitors has been developed. TNF occurs naturally in the body and is a key player in the inflammation process in RA. It is found in high concentration in the joint fluid of people with RA. By attaching to the TNF, these new agents can block its effect.
Infliximab (e.g. Remicade) is a TNF inhibitor available for the treatment of RA in selected patients.
Infliximab slows the progression of RA and reduces joint damage. Infliximab can only be prescribed by certain medical specialists. It is given by infusion via a drip into a vein. Each treatment takes approximately 2 hours.
Infliximab is given in combination with methotrexate. In Australia there are very tight Government restrictions on which patients with RA can obtain access to Remicade as the treatment is expensive.
Etanercept (e.g. Enbrel) is another TNF inhibitor. Enbrel is usually given by injection under the skin twice weekly. It is also expensive.
Enbrel is used for the treatment of active, adult RA in people who have had an inadequate response to several DMARDs, including methotrexate.
It is also used in some other types of arthritis, such as active polyarticular juvenile chronic arthritis in patients (4-17 years) who have had an inadequate response to several DMARDs.
In July 2003, Enbrel was listed on the Pharmaceutical Benefits Scheme (PBS) for selected patients with severe RA. This was followed later that year by the listing of Remicade.
Recently, a third anti-TNF medication, Humira (adalimumab), was added to the list of approved agents for RA. It is administered by injection under the skin, once a fortnight.
In studies, etanercept, infliximab and humira have shown substantial improvements in people with RA. Studies are in progress to evaluate the long-term safety of these powerful and expensive agents, particularly with regard to potential side effects such as increased susceptibility to infection and the development of malignancy.
In the near future we will see other biologicals approved for use in Australia — in summary, an exciting new era is emerging of improved therapy for patients with RA.
Last Reviewed: 16 May 2005
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