Much more than child’s play
Published on 05 December 2014
A new national arthritis treatment centre for children with arthritis - the first of its kind in the country – aims to make a big difference to the way that young patients are treated. Jane Tadman reports.
Six-year-old Lily Whitehead is happily drawing a picture of a flower in the clinical research facility at Alder Hey Children’s NHS Foundation Trust in Liverpool.
Lily has had
juvenile idiopathic arthritis (JIA) since she was three, and for the past year she has been coming to Alder Hey every two weeks for injections of anti-TNF therapy as part of clinical trial, part-funded by Arthritis Research UK.
Clinical nurse specialist Jane Kelly has administered the injection of
adalimumab – having first given Lily a spot of ‘giggle juice’ otherwise known as entonox – and mum Jane says she can’t believe the difference the drug has made to her little girl’s life. Lily went rapidly downhill
Jane and husband Nick, who live in Southport with Lily and their elder daughter, 10-year-old Daisy, were shocked when their younger daughter was diagnosed with arthritis. Lily developed a limp, then rapidly went downhill, with pain and swelling in her knees and ankles leaving her unable to walk. She also developed painful eye inflammation called uveitis.
Remembers Jane: “I had to pick her out of bed to wheel her to the loo, lift her out and then wheel her back to her bed; she was that bad. We got used to it, but it was tough when I look back.”
Lily was recruited onto the trial of assessing the effectiveness of the drug adalimumab compared to placebo a year ago, and she has not looked back since. “It’s been brilliant. Her joints and general movement are so much better and she has lots of energy,” says Jane. “To me it’s like she’s cured.” (As the clinical trial is randomised and double-blinded, Lily may be on either the active drug or the placebo. This will only be established at the end of the trial).
This year, for the first time, Lily was able to take part her school sports day. Adds Jane: “It was fantastic to see her run around the track, particularly as last year it was upsetting for her as she couldn’t join in. But now she’s very sporty – she’s doing gymnastics and is having swimming lessons.”
Going on the drug trial was the right thing for Lily
Jane and Nick had initial reservations about Lily going on a drug trial at the age of four, but staff at the clinical research facility allayed their fears. “I was worried about the drugs being pumped into her, but it was the right thing. We trust the staff here and they know what’s right for her. She has made massive progress. She has her days where she says ‘do I still have to keep going to the hospital?’ And I say ‘As long as you are feeling like this, isn’t it better we keep going?’ And she says, ‘OK’.”
Children like Lily, and those youngsters with arthritis who have not found a drug that controls their condition, will benefit enormously from the launch of the new
Arthritis Research UK National Experimental Arthritis Treatment Centre for Children (EATC) at Alder Hey, the first of its kind in the UK. Speeding up drugs for children with arthritis
The EATC is dedicated to speeding up the development of new drugs for children with arthritis and related conditions, by running small clinical trials of promising drugs currently in the pipeline, and those already used in adult patients.
The centre has identified four priority areas –
juvenile idiopathic arthritis (JIA); JIA-associated uveitis, a potentially serious eye condition that can lead to blindness; childhood lupus; and childhood bone diseases.
Liverpool is already the national co-ordinating centre for all clinical trials involving children in the UK, and benefits from the strong links with the University of Liverpool.
Professor Michael Beresford, director of the EATC, is keen to stress these links – and to point out that only a door and a corridor separate the hospital from the university’s laboratories.
“We collect samples from children with JIA and lupus and they come through the door and straight into the lab to be processed and analysed,” he explains. “Within the hospital here there’s fantastic expertise in looking after children with arthritis, and within the university there’s huge expertise in researching to understand what causes the diseases and running safe, child-friendly drug trials. The EATC is really important in bringing these elements together. Delivering better treatment
“There’s no centre in the country or in Europe that has our focus of drawing together research that combines all the expertise needed to look at what is causing disease and taking that right through into trials, and delivering better treatment.”
Together with Professor Athimalaipet Ramanan and colleagues in Bristol, who lead on JIA-uveitis for the EATC, and Professor Nick Bishop in Sheffield, leading on childhood bone disorders, the EATC will be working very closely with paediatric rheumatology colleagues in Newcastle, London and across the country to develop new and important treatments for children and young people with these disorders.
The university’s research centre, which adjoins the hospital, is a hive of activity. Next to Professor Beresford’s office there are labs where researchers are investigating disease pathways in JIA and childhood lupus, as well as rarer conditions. And next door to the labs, there’s a room full of trial co-ordinators, where a whole range of current and future clinical trials are planned and organised. With Alder Hey’s brand-new £280 million Hospital in the Park due to open in June 2015, along with a new state of the art research and education facility, it’s exciting times for children’s health research. And the EATC is at the heart of these developments.
New belimumab trial for children with lupus
As well as housing a co-ordinating centre for the largest national cohort of children with lupus in the world – they currently have data from over 450 youngsters – and discovering fundamental steps in what causes lupus, the team has recruited the first child to an international trial of belimimab, a promising new drug for lupus in both adults and children. One of the things the new EATC will make possible is testing drugs used in slightly more common conditions such as JIA in rarer conditions such as uveitis and lupus, as well as
Behçet’s, scleroderma and juvenile dermatomyositis.
Not so long ago, drug trials involving children were rare. There was reluctance to conduct studies of medicines in children due to a number of factors, including ethical concerns about conducting trials in children, together with commercial considerations. The number of children in the UK with JIA is roughly 15,000, compared with 380,000 people with rheumatoid arthritis, making trials in children not necessarily financially viable for pharmaceutical companies.
As a result, until recently most drugs have only been tested for safe and effective use in adults, and there are comparatively few medicines on the market which are specifically licensed for the treatment of children with arthritis, such as
etanercept. ( Tocilizumab and canakinumab are both licensed for certain subsets of JIA.) As a result, unlicensed and off-label drugs were prescribed in children, which sometime resulted in inappropriate dosing and unforeseen adverse events.
However, in 2007, European regulations were introduced which made it mandatory for all drug companies to test new drugs on children as well as adults, and as a result the clinical trial landscape has changed out of all recognition.
Improving understanding to improve care
Expectations have changed of what is acceptable. Twenty years ago many children with arthritis ended up in wheelchairs, and there were few effective treatments. Today the outcome for most youngsters is far brighter.
Dr Eileen Baildam, a paediatric rheumatologist at Alder Hey, recalls that when she started working as a consultant in the 1990s there was just one clinical trial involving children.
“It was all the unit could cope with at the time, but also it was thought to be unethical to do trials on children. But oncology – cancer care – changed because every child was on a drug trial,” she says. “Now, with the help of the children themselves, and the Arthritis Research UK clinical studies group, which has really promoted the importance of this work, it’s now felt to be the right of every child with arthritis and related conditions to be involved in drug trials.
Professor Beresford notes: “Every patient at Alder Hey with an inflammatory rheumatic condition is now offered the opportunity to be in a clinical trial or to take part in studies to help improve our knowledge of their disease. We hardly ever get anyone refusing to get involved in studies. It’s an integral part of our care, and our philosophy, and is an essential part of improving the whole knowledge base.”
The team are keen to make the most of their links with leading adult rheumatologists running clinical trials, and the EATC has strong collaborative links with colleagues such as John Isaacs in Newcastle, Iain McInnes in Glasgow and Peter Taylor in Oxford, so they can take advantage of new compounds being discovered as potential targets for new drugs.
Equally important is looking at ways to reduce children’s reliance on very old drugs which are still the mainstay of treatment for many youngsters with severe disease – steroids. Steroids are life-saving and life-transforming over short periods of time because they work quickly to suppress the immune system and hence inflammation but in large doses over long periods their side-effects can be devastating. What’s required is ‘efficacy without toxicity’, as Dr Baildam puts it.
“Steroids are still widely used via injections into the joint, intravenously, as topical creams, or even drops in the eyes, but we want to be able to treat children without them, and to do that we have to understand the disease better and be able to select drugs that are more specific and don’t have the side-effects,” adds Professor Beresford. “Within the EATC we want to improve our understanding, in order to improve our care.”
Which sums up the centre’s vision in a nutshell.
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