Rheumatoid arthritis: prescription medicines
If you have rheumatoid arthritis (RA), prescription medicines will be an important part of your treatment plan. Although these medicines do not cure RA, they can suppress inflammation, prevent joint damage, reduce disability and relieve symptoms. It is important that you understand your medication options, so that you can get the most out of the treatments that your doctor prescribes.
Medicines for treating rheumatoid arthritis include:
- disease-modifying anti-rheumatic drugs - medicines that can suppress or reduce inflammation and help prevent joint damage; and
- medicines to reduce pain and disability.
People with rheumatoid arthritis are usually under the care of a rheumatologist (specialist in musculoskeletal diseases). Your rheumatologist will work with you to develop a personalised self-management plan. This plan should detail what action to take if you have a flare-up and when to see your doctor.
Disease-Modifying Anti-Rheumatic Drugs (DMARDs)
Active rheumatoid arthritis often results in gradual destruction of the affected joints and eventual disability. Disease-modifying anti-rheumatic drugs (DMARDs) work by suppressing inflammation to induce and maintain remission - in other words, make the disease inactive. (Without treatment, rheumatoid arthritis rarely goes into remission on its own.)
Suppression of inflammation with DMARDs also helps reduce the risk of cardiovascular disease (such as heart attack and stroke) in people with RA. That’s because chronic (ongoing) inflammation increases the risk of cardiovascular disease.
DMARDs usually need to be taken long term, and may take a few months for their effects to be seen.
To get the best outcome, rheumatologists usually recommend starting DMARDs when RA is first diagnosed, which helps prevent the development of joint destruction, deformity and disability. However, there are benefits from starting treatment with DMARDs at any time in the illness.
There are several types of DMARDs, including:
- conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs);
- targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs); and
- biological disease-modifying anti-rheumatic drugs (bDMARDs).
DMARDs are powerful medicines that can cause some serious side effects. Side effects that have been associated with all types of DMARDs include:
- increased risk of infections and serious infection (especially when a combination of DMARDs that includes a biological DMARD is used);
- suppression of the production of blood cells in the bone marrow;
- liver damage; and
- an increased risk of developing certain cancers.
Many DMARDs should not be taken during pregnancy, and some should be stopped at least 6 months before becoming pregnant. Women who are planning a pregnancy should talk to their doctor about which medicines are suitable during pregnancy.
Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs)
csDMARDs are usually the first medicines prescribed to suppress inflammation in RA, and include the following.
- Methotrexate (e.g. Methoblastin, Trexject) is the most commonly used DMARD. It can be given as tablets or an injection once a week. Methotrexate is potentially toxic to the liver, and alcohol consumption should be avoided if you are taking it. Other side effects include hair loss (which is usually reversible once the medicine is stopped) and pneumonitis (inflammation of the lungs). Supplements of folic acid are recommended when taking methotrexate to help minimise side effects such as nausea and mouth ulcers and to help prevent liver toxicity.
- Leflunomide (brand names Arabloc, Arava) is given as a daily tablet. It can be used on its own to treat people with severe, active RA who do not respond to methotrexate, or in people who cannot take methotrexate. Possible side effects include reversible hair loss, high blood pressure, pneumonitis and peripheral neuropathy (problems with the nerves in the arms and legs).
- Sulfasalazine (e.g. Pyralin EN, Salazopyrin) tablets can be 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.
- Hydroxychloroquine (brand name Plaquenil Tablets) is a medicine used in the treatment of malaria that can also be used in the treatment of mild RA. This medicine is less toxic than some of the other treatments. Rare side effects include eye problems, sensitivity to the sun and anaemia. You will need to see an eye specialist periodically if you are taking this medicine.
Some people may need to take a combination of several different csDMARD medicines. Methotrexate may be used in combination with leflunomide, sulfasalazine or hydroxychloroquine in people with with active, severe RA, or those with a poorer outlook. It usually takes at least 6-8 weeks of treatment for the medicines to take full effect.
Older, conventional DMARDs that are now rarely used include gold, azathioprine and ciclosporin. These medicines have largely been replaced by newer medicines that are more effective and have fewer serious side effects.
Targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs)
Tofacitinib (brand name Xeljanz) is the only targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD) currently available in Australia. Tofacitinib is a Janus Kinase (JAK) inhibitor that works by reducing immune and inflammatory processes. It is given as a tablet once a week. It may be recommended if csDMARDs have not been effective.
Side effects include liver problems, high cholesterol, and a risk of infections such as shingles.
Biological disease-modifying anti-rheumatic drugs (bDMARDs)
This new class of medicines targets substances in the immune system involved in inflammation. Biological disease-modifying anti-rheumatic drugs (bDMARDs) may be used in combination with csDMARDs if csDMARDs have not been effective on their own in treating rheumatoid arthritis.
The first group of bDMARDs to become available were the tumour necrosis factor (TNF) inhibitors (also called TNF antagonists). TNF occurs naturally in the body and is a key player in the inflammatory process in RA. By attaching to the TNF molecule or its receptors on cells, TNF inhibitors can block its effect.
TNF inhibitors available in Australia for the treatment of RA include the following.
- Infliximab (brand name Remicade) - given by infusion via a drip into a vein. Each treatment takes approximately 2 hours. Infliximab is given in combination with methotrexate.
- Etanercept (Enbrel) - given by injection under the skin once or twice weekly.
- Adalimumab (Humira) - administered by injection under the skin, once a week or once a fortnight.
- Certolizumab pegol (brand name Cimzia) - given by injection under the skin.
- Golimumab (brand name Simponi) - given once a month by injection under the skin.
Other bDMARDs include:
- Abatacept (brand name Orencia) - a monoclonal antibody targeted at specific molecules found on T lymphocyte cells. It is given as a monthly intravenous infusion or injection under the skin. High blood pressure is a possible side effect.
- Tocilizumab (brand name Actemra) - an interleukin-6 (IL-6) inhibitor given as a monthly intravenous infusion or monthly injection. Possible side effects include high blood pressure and high cholesterol.
- Rituximab (Mabthera) - a monoclonal antibody targeted against certain white blood cells called B lymphocytes. It is given as 2 intravenous infusions 2 weeks apart. Sometimes this course may need to be repeated.
- Anakinra (Kineret) - an interleukin-1 (IL-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 (under the skin) injection once daily.
People taking biological DMARDs are at risk of developing infections. There is also a risk of allergic reactions and reactions at the injection site (area that the medicine is injected) with these medicines.
Monitoring of DMARDs
Before starting on DMARDs, your doctor will ask about any infections you’ve had in the past and whether you have any risk factors (such as overseas travel) for certain infections. Tests are also usually recommended to check whether you are immune to certain infectious diseases (including hepatitis, shingles and tuberculosis), and to check your overall health.
Your doctor will want to make sure that your are up-to-date with all recommended vaccines before starting treatment, because DMARDs can increase your risk of infections.
While you are being treated with DMARDs you’ll need to have regular tests to make sure the medicines are working and not causing any serious side effects.
The effectiveness of DMARDs - how well they are suppressing inflammation - can be measured by:
- blood tests called inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), which indicate the level of inflammation in the body; and
- the number of painful, swollen or tender joints in the body.
Your doctor may also recommend regular X-rays and joint ultrasounds to check for joint damage.
Regular blood tests to monitor for side effects of DMARDs will depend on the medicine you are taking, but may include:
- full blood count (FBC);
- kidney function tests (urea, creatinine and electrolytes);
- liver function tests (LFTs);
- blood sugar level (BSL) and glycosylated haemoglobin (HbA1c);
- plasma immunoglobulins; or
- cholesterol levels.
Urine tests and blood pressure checks may also be recommended to monitor for side effects of some DMARDs.
Corticosteroids are very effective anti-inflammatory medicines that can also help control disease in rheumatoid arthritis. Corticosteroids are often prescribed short-term to control symptoms quickly in people who have recently been diagnosed with RA.
Corticosteroids may be given as tablets or an injection (either into a vein or muscle). They are associated with significant adverse effects, such as weight gain, diabetes, hypertension (high blood pressure), mental health problems and osteoporosis, and for this reason they are not usually used long-term.
Corticosteroids can also be given to treat a flare-up of RA. Your doctor may recommend tablets, injections into a muscle or injections into the inflamed joint(s). Joints commonly injected are fingers, toes, knees and shoulders.
Medicines to manage rheumatoid arthritis symptoms
People with RA can have painful joints even when taking DMARDs. Painkillers are often recommended to relieve pain and also to reduce disability.
Paracetamol can effectively relieve mild to moderate pain and is relatively safe.
Fish oil has been found to have a mild anti-inflammatory effect, and may help people with mild pain associated with RA. It may take up to 3 months for a daily dose of omega-3 fish oil to have any noticeable pain-relieving effects. Fish oil is associated with few side effects, but can cause a ‘fishy aftertaste’, heartburn and diarrhoea.
Non-steroidal anti-inflammatory drugs (NSAIDs) can relieve pain and reduce inflammation. Some NSAIDs, such as ibuprofen (e.g. Nurofen, Rafen, Advil) are available over-the-counter, while others, such as diclofenac (e.g. Voltaren, Fenac), piroxicam (e.g. Feldene, Mobilis), sulindac (Aclin), ketoprofen (Orudis, Oruvail), naproxen (Inza) and indomethacin (e.g. Indocid, Arthrexin), are available on prescription.
NSAIDs are associated with an increase in the risk of:
- upper gastrointestinal problems (such as abdominal pain, peptic ulcers, ulceration of the oesophagus and gastrointestinal bleeding - these side effects are more common with prescription than over-the-counter NSAIDs);
- kidney problems; and
- cardiovascular disease (heart and blood vessel disease including heart attack, high blood pressure and stroke).
The COX-2 selective inhibitors, also called coxibs are a type of NSAID that have lower rates of gastrointestinal side effects associated with them than other NSAIDs. Examples include celecoxib (brand names Celebrex, Celaxib, Kudeq) and meloxicam (Mobic, Moxicam).
You can discuss the risks and benefits of treatment with NSAIDs with your doctor, who will be able to tell you whether or not they are suitable for you and which type will suit you best.
2. Principles of analgesic and anti-inflammatory drug use for musculoskeletal conditions in adults (published Mar 2017). In: eTG complete. Melbourne: Therapeutic Guidelines Limited; 2017 Jul. http://online.tg.org.au/complete/ (accessed Aug 2017).
3. Wilsdon TD, Hill CL. Managing the drug treatment of rheumatoid arthritis. Aust Prescr 2017;40:51-8. https://www.nps.org.au/australian-prescriber/articles/managing-the-drug-treatment-of-rheumatoid-arthritis (accessed Aug 2017).