SYCAMORE Trial Summary

uvenile idiopathic arthritis (JIA) is the name for a type of arthritis that primarily affects young people and whose cause is unknown. ‘Arthritis’ means inflammation of the joints, but in JIA the inflammation could also affect the eyes and internal organs.

Approximately 1 in 1000 children in the UK develop JIA. Both boys and girls are affected and of those children with JIA around 30-40 % are at risk of inflammation of the uvea in the eye, known as uveitis. In one third of the children who develop uveitis, the disease is of significant severity to cause visual loss, cataracts, increased pressure in the eye and blindness. The severity of the disease is partly due to the level of damage in the eye already present when the diagnosis is made.

The current treatments include steroid eye drops and those with moderate or more severe disease will be treated with methotrexate. This is either as a medicine or tablets, or injected into the fatty layer just under the skin (called a subcutaneous injection). These treatments do not cure the uveitis or JIA but reduce inflammation, so relieving symptoms and reducing the level of permanent damage.

Even when treated with methotrexate, the majority of children with moderate to severe disease continue to have active inflammation in the eye and lose significant vision in one eye and end up certified blind as a result of uncontrolled inflammation.

TNF is a protein in the body which is involved in inflammation processes. TNF has been shown to be important in the inflammation seen in both the arthritis and uveitis caused by JIA. Some research has shown that treatment with drugs that block the action of the TNF protein (called anti-TNF drugs) may help reduce symptoms of swollen joints in children with JIA. Adalimumab is an example of an anti-TNF drug which has been shown to be helpful in these circumstances. It is given as a subcutaneous injection every fortnight. There are indications that adalimumab may also be effective in treating uveitis symptoms, but the only way to test this properly is to carry out a research project called a clinical trial, which has not yet been done.

This clinical trial will test whether adding adalimumab to the methotrexate treatment for children with severe uveitis will enable us to prevent the serious complications that can occur from uncontrolled uveitis in children with JIA. In this clinical trial we will recruit 114 children with severe uveitis. All children will receive subcutaneous methotrexate. The purpose of this clinical trial is to examine how effective the addition of adalimumab is for treating their uveitis symptoms. The only way of testing this accurately is to compare children who are treated with methotrexate plus adalimumab against children who are treated with methotrexate plus a treatment that looks exactly the same as the adalimumab but contains no medicine (called a ‘placebo’). We would allocate the different treatments at random, which is a bit like throwing a dice to decide. No one would know in advance which treatment a child will get. This sort of study is called a randomised controlled trial or RCT. We use a placebo and carry out RCTs so we can be sure the information provided about the treatment is fair and has not been swayed by knowledge of whether it is the test medicine or the placebo that is being given. Children will be treated initially for 18 months and will be monitored very closely throughout to look for improvement or worsening of the inflammation. Those children whose eyes do not improve, or worsen, whilst receiving their randomised treatment will be classed as treatment failures. Treatment failures will stop trial treatment and be treated with alternative therapy as determined by their ophthalmologist and Rheumatologist. After the 18 months trial period, all children will continue to be followed up for a further 6 months as part of the study for a total 2 years follow up.

This trial will be carried out in hospital outpatient departments by a network of doctors experienced in the treatment of JIA and uveitis. If this trial shows that adalimumab is effective in treating children with severe uveitis, this would result in better control of inflammation in children with this severe eye complication of JIA and would hopefully decrease the proportion of children who develop serious visual complications and blindness from uncontrolled uveitis.