DMARDs used in the Treatment of RA

DMARD

TYPICAL DOSES

COMMENT

Methotrexate

Varies between 7.5 – 25 mg/week

This drug has been available for over 30 years and was originally established for use in cancer treatment and is still used for that purpose. However at very small doses it can be very effective for the treatment of rheumatoid arthritis and childhood forms of arthritis. It is probably the most effective drug for rheumatoid arthritis we currently have and is typically first or second choice DMARD treatment. It acts by suppressing the immune system and can slow down the progress of arthritis as well as making significant improvements in general wellbeing by reducing the inflammation.

Sulfasalazine

Between 1.5 and 3 grams per day (40mg/kg/day)

Sulfasalazine has been available since the 1940s and it is a combination drug containing an anti-inflammatory compound and an antibiotic. It is unclear how it works but it clearly does work for a large number of patients with arthritis. It is also used for the treatment of inflammation of the bowel. Like methotrexate it can damp down the immune system and ongoing monitoring is required for both these drugs.

Leflunomide

10-20 mg/day

Leflunomide is a relatively new agent introduced specifically for treating rheumatoid arthritis within the last 10 years. It has a particular effect on the lymphocytes which are the main cells involved in the arthritis process. It is likely to regulate the immune system by damping down the overactive lymphocytes but like other drugs it does have other side effects and therefore monitoring of blood count and liver function is necessary. Leflunomide may also cause high blood pressure and occasionally cause diarrhoea.

Azathioprine

Typically 2-2.5mg/kg/day

Azathioprine is a cytotoxic drug which is very widely used for damping down the immune system. It slows down the rate at which cells divide and the aim is to slow down the rate of cell division amongst the inflammatory cells. Typical side effects would include sickness and diarrhoea. It can lower the white cell count and platelet count, making you more prone to bruising, bleeding and infection.

Penicillamine

500 – 1000mg/day

Penicillamine is a very old drug for treatment of rheumatoid arthritis. Its mechanism of action is uncertain: it seems to damp down the immune system in a non-specific way. It must be taken as a single dose away from food because otherwise it binds food and does not get absorbed into your body and therefore won’t do you any good. It can have a number of side effects including sickness and diarrhoea, it can also cause skin rashes. Blood testing is necessary with blood count, and urine testing in case it has caused a small leak of protein through the kidney.

Injectable Gold

50mg/week – 50mg/month

Injectable Gold has been around since about the 1920s and was originally introduced as a way of treating what was thought to be an infectious cause of arthritis. Since then it has been shown that gold is not a good anti-infection drug and that arthritis is not caused by infection. Nevertheless the drug does seem to have some value when given over a long period of time by repeated injection. Like other non-specific DMARDs it damps down the immune system and seems to calm down arthritis. It has a number of side-effects similar to penicillamine: it can cause skin rashes, nausea and diarrhoea. Blood testing is necessary to look for any reduction in the cell count and a urine check is required to look for any evidence of a protein leak through the kidney.

Hydroxychloroquine

6.5mg/kg/day, typically 200-400 mg/day

Hydroxychloroquine is a treatment for malaria but has been shown to damp down the immune system in a non-specific way. It is used widely for the treatment of lupus (SLE) but is also an established drug for the treatment of mild rheumatoid arthritis. The main side effect is of accumulation of the drug in the back of the eye if too much is given over too long a period of time. This can cause an interference with night-time vision and should be discussed carefully with your doctor before starting the treatment. If you have had a previous problem with your eyesight it may be best to see an eye specialist prior to starting treatment. No blood tests are required whilst receiving hydroxychloroquine.

Ciclosporin

2.5-4mg/kg/day in two divided doses

Ciclosporin is an established treatment to suppress the immune system in patients who are about to undergo kidney or heart transplant. Its effects on the immune system have been used for the treatment of patients with rheumatoid arthritis and it does seem to have an influence on the activity of the arthritis. Common side effects include a rise in blood pressure, increased hairiness, increased swelling of the gums and increased tendency to infection. There is also a risk of kidney disease on the drug including high blood pressure and interference with kidney function. The drug has to be monitored carefully, checking blood pressure and checking bloods regularly.

Etanercept

Typically 50mg/week, either as a single injection (subcutaneous) or as two injections on separate days of 25mg each.

Etanercept is one of the newer anti-TNF treatments. It is a receptor protein which binds to TNF (tumour necrosis factor) which is one of the most important inflammatory chemicals produced in patients with arthritis. TNF is important for normal health and it is not a good idea to block all TNF in the body, otherwise patients are at risk of infection. Etanercept is usually well tolerated, sometimes patients can experience a local reaction at the injection site of skin redness and soreness. This can be avoided in most instances by varying the site of the injection on each occasion over a cycle of 4-5 weeks (eg inject the outer side of the left thigh on the first week, the inner side of the left thigh on the second week etc). Most patients can give themselves their injections. No routine monitoring is required whilst on this drug but all patients should be attending hospital regularly for review.

Infliximab

Typically 3 mg/kg intravenous infusion every 8 weeks

Infliximab was the first anti-TNF treatment to be established in rheumatoid arthritis. It has to be given by hospital doctors and nurses to ensure safety precautions are adhered to. It is used very widely for rheumatoid arthritis and directly blocks TNF by binding the normal TNF receptors instead of TNF. Too much reduction of TNF activity is harmful and may lead to susceptibility to infection, particularly tuberculosis. No specific blood tests are required but all patients should be under regular hospital review. Initial doses of infliximab are given more frequently to establish good control of the disease (the first 3 doses are all given within an 8 week period).

Adalimumab

Typically 40 mg every 2 weeks given by subcutaneous injection

Adalimumab is the newest of the anti-TNF drugs. It blocks the effects of TNF and like other anti-TNF drugs it has the potential to cause infection by suppressing too much TNF. All patients who are on this treatment must be under regular review by the hospital.