Methotrexate and DMARDS

Disease Modifying AntiRheumatic Drugs (DMARDS) are increasingly used to treat Juvenile Idiopathic Arthritis (JIA) and other inflammatory diseases. The exact mechanism of their actions remains unclear. 

• Clinical nurse specialists have an essential role in educating and counselling patients and families to have a full understanding - why they are being used, how to deliver the treatment at home (if appropriate), the need for monitoring, advice on vaccines and how to seek help if there are side effects.

Methotrexate (MTX) is the most widely used DMARD in paediatric rheumatology.

Royal College Guidance on the use of MTX is available and gives very useful practical advice on its use in children and supporting parents to deliver this at home.

• MTX is given once a week, by tablet or liquid, but the preferred route is by subcutaneous injection (which can be delivered and administered at home).  MTX is often well tolerated, can provide good disease control and has long term safety data.
• Patients and families are usually encouraged if possible to give MTX at home and normalise treatment. Local community-based nurses may provide support at home or administer MTX if necessary. In the UK guidance is offered regarding the training and support of non-specialist nurses required to administer MTX.
• MTX is a teratogen and pregnancy should be avoided whilst taking this drug - this advice also applies to males who should not father a child whilst on MTX. Appropriate advice regarding contraception is needed. Successful pregnancy when no longer taking MTX is possible and females need to be reassured that they are not infertile as a result of taking MTX.
• MTX needs to be monitored for side effects (cytopenia, abnormal liver function tests) although these are rare. Mild elevation of serum liver enzymes and mild bone marrow suppression are uncommon, often transient and related to intercurrent infection. Nausea is often the main reason for stopping MTX or switching to other drugs including biologics. Strategies to minimise nausea involves omitting NSAIDs on the day of MTX administration, administering the drug on a weekend evening preceded by an anti-emetic and continuous low dose folic acid supplementation. Long term use of MTX (>30 years) demonstrates a good safety profile although there is potential of long term unknowns including impact on fertility and malignancy risk. Live vaccines are contraindicated and annual influenza vaccine are recommended.
• MTX is slow to take effect (often 3 months) and in JIA, often other measures, such as joint injections or intravenous or oral steroids may be used as bridging agents. MTX is usually started immediately after the diagnosis is confirmed in all types of JIA other than oligoarticular JIA (joint injections are first line), although in the latter, MTX is used in oligoarthritis that is extending or failing to respond to intra-articular corticosteroids or a critical joint is affected (e.g., hip, wrist)

Other DMARDs, including sulphasalazine, azathioprine, ciclosporin, leflunamide and thalidomide can be useful.

• The use of gold, penicillamine and hydroxychloroquine has dramatically reduced as they have been shown to be much less effective than MTX in JIA management. Hydroxychloroquine may be useful in Juvenile Systemic Lupus Erythematosus (JSLE); especially to help skin disease and may reduce cardiovascular risk. Sulphasalazine can be useful in oligoarticular JIA or enthesitis related arthritis. In the child with severe disease, who is resistant to or intolerant of MTX or other DMARDS, biologic therapies are often used although for many parts of the world, access to these is very limited due to their high cost.

Mycophenolate Mofetil (MMF)

• MMF is most widely used in the treatment of vasculitis (including JSLE) and takes approximately 2-4 months to achieve full effect.
• Patients taking MMF are immunosuppressed during and for ≥ 3 months after stopping treatment
• The need for monitoring and advice regarding vaccination and avoidance of pregnancy are the same as for MTX (see above). 

Azathioprine

• Azathioprine is mainly used primarily to treat vasculitis or Inflammatory Bowel Disease and takes approximately 2-4 months to achieve full effect.
• The need for monitoring and advice regarding vaccination and avoidance of pregnancy are the same as for MTX (see above).