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.