Rheumatoid arthritis: prescription medicines
Whatever form of arthritis you may have, medicines 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 medicines which 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 fully 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. It usually takes at least 6-8 weeks to achieve a beneficial effect. 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 performed to identify potential adverse effects.
Here are some of the DMARDs that are used in the treatment of RA.
- Methotrexate (e.g. Methoblastin) is the most commonly used DMARD. It can be administered either orally or intramuscularly. Supplements of folic acid are required to help minimise side effects such as nausea and mouth ulcers. Methotrexate is potentially toxic to the liver, and alcohol consumption should be avoided if you are taking it. Methotrexate is considered to be the gold standard DMARD against which other agents are compared.
- Sulfasalazine (Pyralin EN and Salazopyrin) 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. These are less common once the maintenance dose is achieved. More seriously, it occasionally causes severe anaemia.
- Leflunomide (Arabloc and 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 (Myocrisin) have a significant clinical benefit in the treatment of patients with RA. These are, however, now used rarely as other DMARDs have fewer adverse effects. Side effects of gold injections include 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 (Ridaura) is now rarely used, largely because of poor efficacy. Diarrhoea is a common side effect.
- Antimalarials such as hydroxychloroquine sulfate (Plaquenil) are used in the treatment of mild RA. Their overall effects are mild, but they are less toxic than some of the other treatments. Hydroxychloroquine is often used in combination with other DMARDs. Rare adverse effects include retinal toxicity. You will need to see an eye specialist periodically if you are taking this medicine.
- Cyclosporin (Cicloral, 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. It shows clinical benefit in people with RA but produces many adverse effects, including hypertension (high blood pressure) and impaired renal (kidney) function.
- Azathioprine (e.g. Imuran) is now limited to the treatment of severe active RA that is unresponsive to other DMARDs and to treat people with rheumatoid vasculitis (a serious complication of severe RA in which blood vessels are inflamed). 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) and naproxen sodium (e.g. Naprogesic), are available over the counter, while others, such as diclofenac (e.g. Voltaren), piroxicam (e.g. Feldene), sulindac (Aclin) and indomethacin (e.g. Indocid), 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 medicines. 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, sometimes known as glucocorticoids, such as prednisone (e.g. Panafcort) and prednisolone (e.g. Panafcortelone), are powerful agents that work by reducing inflammation and suppressing the immune system. They are used in the treatment of RA, both as tablets and as injections into the joint.
Prednisolone is sometimes used for 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 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 or given via an intravenous infusion.
More recently, another category of arthritis treatments called biologics has been developed. The first group to become available were the tumour necrosis factor (TNF) inhibitors. TNF occurs naturally in the body and is a key player in the inflammatory process in RA. It is found in high concentration in the joint fluid of people with RA. By attaching to the TNF molecule or its receptors on cells, these new agents can block its effect.
Three TNF inhibitors are available in Australia for the treatment of RA.
- Infliximab (Remicade) is used for the treatment of RA in certain groups of people. It slows the progression of RA and reduces joint damage. 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 be treated with infliximab.
- Etanercept (Enbrel) is used for the treatment of active RA in adults who have had an inadequate response to several DMARDs, including methotrexate. It is given by injection under the skin once or twice weekly.
- Adalimumab (Humira) is the third TNF inhibitor that has been added to the list of approved agents for RA. It is administered by injection under the skin, once a fortnight.
These three TNF inhibitors are listed on the Pharmaceutical Benefits Scheme (PBS) for specific groups of people with severe active RA. They can only be prescribed by certain medical specialists (rheumatologists and clinical immunologists).
They are also used to treat other types of arthritis. Etanercept and adalimumab are used to treat active polyarticular juvenile chronic arthritis (in children aged 4-17 years), and all three TNF inhibitors are used to treat psoriatic arthritis.
In studies, etanercept, infliximab and adalimumab have been shown to provide substantial improvements in people with RA. Studies to evaluate the long-term safety of these powerful and expensive agents, have found, in addition to some other side effects, a slightly increased susceptibility to infection in people taking these medicines.
Newer biologic agents
Over the past few years several new biologic agents have been developed which target substances in the body other than TNF. Many of these have been used to treat people with RA and are now available on the PBS.
- Rituximab (Mabthera) is a monoclonal antibody targeted against certain white blood cells called B lymphocytes. (Monoclonal antibodies are proteins that are produced in the laboratory to recognise and bind to proteins found in the body.) Rituximab is an effective treatment in people with RA. Government (PBS) funding is available for rituximab to be used to treat RA in people who have not responded to treatment with a TNF inhibitor. It is given as 2 intravenous infusions 2 weeks apart.
- Abatacept (Orencia) is another monoclonal antibody targeted at specific molecules found on cells called T lymphocytes. It is given as a monthly intravenous infusion. It is used to treat people with RA who have not responded to treatment with several DMARDs including methotrexate.
- Anakinra (Kineret) is called an interleukin-1 antagonist. It blocks the action of interleukin-1, a protein present in the body that is produced in high concentrations in people with RA. Anakinra is given by subcutaneous injection. A 2009 Cochrane review concluded that Anakinra has a modest effect in people with RA.
It is likely that a number of other biologic agents will become available in the future for the treatment of RA.
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