Drug Therapy

Medical Therapy for JIA

The aim of medical treatment is to improve the arthritis as quickly as possible in all the affected joints. This is often done with several medications initially and then once the joints are better some medications can be stopped. This will reduce pain and stiffness in the joints. This will also prevent damage to the joints. The child is then able to participate in an active exercise programme which keeps the muscles around the joints strong, keeps the joints moving, and reduces the tendency to thinning of the bones. What is chosen will depend on the pattern of the arthritis.

Anti-Inflammatory Drugs | Corticosteriods | Slow Acting Drugs | Other Measures

Anti – Inflammatory Drugs

There are many different non-steroidal anti-inflammatory drugs (NSAIDs) which help control symptoms such as pain and stiffness in the joints.

NSAIDs are often used initially as they work quickly and are well tolerated. The amount given is worked out according to the weight of the child. Those approved for use in this country are: ibuprofen (brufen), naproxen (naprosyn), diclofenac (voltarol), and piroxicam (feldene). Nevertheless all drugs can have side effects, so when your child is prescribed one of these drugs, it is important to note any loss of appetite or tummy pain and report it. Other problems include rashes, particularly on exposure to sun, and sometimes headaches.

Ibuprofen is generally well tolerated. There is a liquid preparation which can be used in young children. As it only works for about 6 hours it must be given in 3 or 4 doses every day. It is often useful in reducing fever – at such a time the dosage may be temporarily increased and reduced as the fever improves.

Junifen is available in any chemist shop for the relief of mild to moderate pain in children more than one year old. It contains ibuprofen and therefore should not be given to any child receiving anti-inflammatory drugs without talking to your doctor first. It can be used instead of ibuprofen syrup, and being a sugar-free preparation it is better for the teeth.

Naproxen is also available in liquid form although sometimes hard to obtain. It’s advantage over ibuprofen is that it lasts for a longer time in the body and therefore needs to be given only twice a day. Very occasionally naproxen suspension can cause diarrhoea. Sun sensitivity seems more common than with other drugs, beware of holidays in the sun – both abroad and in the UK!

Diclofenac is available in a suppository especially designed to relieve pain and fever in children. Although the suppository can help morning stiffness in children with arthritis, most people prefer something by mouth. This drug is available in a 50mg dispersible tablet, but as it needs to be given 3 times a day, it is important to follow the instructions given carefully. The 25mg tablet is small so that many older children have no trouble swallowing it. Slow acting tablets are also available, but the child needs to be 9 or 10 years old and to have reached a certain weight before these are used.

Piroxicam need only be given once a day as it lasts for 24 hours. There is a form which dissolves in water and another which melts in the mouth. It does seem however to cause a slightly higher incidence of tummy upsets than the other anti-inflammatory drugs.

Cortocosteroids (Steroids)

These are powerful drugs which reduce severe inflammation, but the exact way they work is not known. They are given by mouth or by injection intravenously when a child is generally ill (systemic disease), for severe polyarthritis or general deterioration (e.g.anaemia, weight loss) with an increasing number of joints affected. Steroids that are injected directly into the joints under general anaesthetic or Entonox (laughing gas sedation) are an excellent way of treating the inflammation in the joints and the preferred way especially in treating oligo-arthritis, and do not have the side effects of steroids by mouth. This will allow the child to move the joint better and far quicker than other treatments. The parent and child will also be shown exercises and be told when to start them after the injection. Steroid drops are available for eye inflammation.

Prednisolone is an oral corticosteroid and is a very effective anti-inflammatory agent. When high doses have to be given every day or more than once in any one day, side effects can occur. Resistance to infection can be reduced and there is also a risk of an infection, such as chicken pox, being more serious in a child who has been on prednisone. Therefore it is vitally important that your doctor knows that your child is on prednisone.

Longer term side effects of prolonged treatment with high dose prednisone can include the child becoming cushingoid. The term refers to a typical appearance of a round face. Such a child fails to grow normally, the bones can become thin and the skin bruises easily; very occasionally the blood pressure goes up. Another rare problem is the formation of cataracts in the eye.

When a child has systemic illness, particularly when there are complications such as inflammation of the covering of the heart (pericarditis), it will be necessary to give the drug on a daily basis. Indeed if a child is extremely ill, it may sometimes be necessary to introduce the drug by means of an intravenous drip (‘pulse’), so that it gets directly into the circulation. This may be repeated on several occasions. Sometimes a ‘pulse’ will cover a period of illness or infection so that the dosage by mouth does not need to be increased.

Steroids must never suddenly be stopped. You should be given a ‘blue steroid card’ at the commencement of your child’s treatment and this must always be presented to any doctor or dentist treating your child.

For older children a ‘Medic Alert’ bracelet or necklace can be worn.

Slow – Acting Drugs

These drugs seem to reduce the overall activity of the arthritis, and therefore can sometimes be called ‘disease modifying anti-rheumatic drugs’ (DMARDs). They are used early on now once the arthritis has been controlled quickly with steroids as above. Before any of these drugs are used, the doctor will discuss with you why this particular drug is being suggested and why your child has to have regular checks while taking it.

Methotrexate has been shown to be of particular value in childhood arthritis. This belongs to a group of drugs called anti-metabolites’, which interfere with cells dividing. Side effects can include nausea, ulcers in the mouth, skin rashes, disturbance in the function of the liver and very occasionally interference with the white blood cells, platelets and red blood cells. It is given as a weekly dose either by mouth or by injection.

Blood tests are necessary to check the blood count and liver function. If your child is having methotrexate you may be asked to give them folic acid between each dose of methotrexate, as it seems to protect against side effects. While good for the joints, it is still not clear whether methotrexate helps to damp down the fever and systemic illness in systemic arthritis.

Leflunomide (Arava) works in a similar way to methotrexate and is sometimes used when children do not tolerate or respond to methotrexate

Sulfasalazine (salazopyrin) has been shown to be an effective drug in children who have enthesitis related arthritis. The majority of these are boys.

It is given by mouth and there is both a suspension and tablet form. It can cause nausea, loss of appetite, rash and temperature; and again regular blood tests looking at the white blood cells and liver function are required.

Biological Treatment

Anti-TNF Treatment
In the last decade treatment to block Tumour Necrosis Factor (TNF), a chemical in the body that mediates arthritis, have been developed. These are given by injection and include currently etanercept given by subcutaneous injection once or twice a week, infliximab given by infusion in hospital and adalimumab given once a fortnight by subcutaneous injection. These are generally reserved for patients where methotrexate has not been effective or have developed side effects from methotrexate. There are usually few side effects compared to other treatments but infections can sometimes occur more often and in particular old TB can be reactivated so this is screened for.

Other Biologic Agents
There are now many biologic agents that block various other cytokines such as IL1 and IL6 that mediate disease especially in Systemic Onset JIA. These are usually only prescribed by highly specialised centres but can be given locally and some are given as a daily injection at home

Other Measures

Children with systemic arthritis are often anaemic because the body is not able to make haemoglobin satisfactorily while inflammation is present. Iron tablets will not help them. Occasionally children may become deficient in iron for a number of other reasons and then tablets or liquid will need to be prescribed.

Intravenous gammaglobulin
Controlled trials have shown this to be no better than placebo (dummy injections) in the majority of patients.

However, occasionally a child will be given intravenous gammaglobulin to try to control serious systemic illness, when the response to corticosteroids is poor.

Growth Hormone

Children with certain systemic chronic diseases, including systemic onset juvenile arthritis, may not grow. Children with active disease do not grow normally and their growth can be further hindered by corticosteroids.

Those no longer on steroids, or only a small dose, may have their growth improved by a course of injections of synthetic growth hormone preparations every day or at least 6 out of 7 days a week. Those whose disease is very active or are on high doses of steroid do not grow as well.

Diet and vitamin supplements

Drug therapy is only one part of the management of children with arthritis. General measures include a healthy diet making sure that the amount and type of food eaten will give enough calories and protein for growth, and calcium to keep the bones as strong as possible.

If your child is eating well there is no need to give vitamins. If the appetite is poor, there is no harm in giving a multivitamin preparation. Similarly, a single dose of cod liver oil each day may reassure parents that the child is getting enough vitamin D.

An extra supplement of calcium as well as vitamin D is necessary to minimise thinning of the bones in children on corticosteroids.

Dr. Nathan Hasson, Consultant Paediatrician and Paediatric Rheumatologist, The Portland, Hospital London