Development of a new method to measure methotrexate levels in children with Juvenile Idiopathic Arthritis (JIA) and Juvenile Dermatomyositis (JDM)
Professor James McElnay
Type of grant
Clinical Studies Group
Queen's University Belfast
Grant reference number
Juvenile idiopathic arthritis, Rheumatoid Arthritis
What are the aims of this research?
We want to develop a method to measure methotrexate (MTX) product levels in blood in children with arthritis using simple finger prick blood samples known as dried blood spots (DBS). We will determine if this method can be used by children and their parents or guardians to participate effectively in DBS sampling in their own home.
Why is this research important?
Juvenile idiopathic arthritis and Juvenile dermatomyositis are both autoimmune diseases, in which the immune system attacks its own tissues. They can have serious consequences including joint destruction and disability, and if the major organs become involved can even result in death. The most important, first line therapy for both these diseases in children is the anti-inflammatory agent MTX.
Around 95% of a given MTX dose is eliminated from the body within 24 hours so there is no value in monitoring blood concentrations of the drug. However, once MTX enters the cells, it undergoes a process resulting in a group of products named ‘methotrexate polyglutamates'. These products are retained for a long time after MTX has been administered and could be a useful marker to assess long-term MTX therapy. However currently measuring these products requires taking relatively large blood samples which is invasive and usually requires a trip to the hospital. Using DBS to collect blood from a simple finger prick would overcome both ethical and clinical issues around taking blood in very young children.
DBS samples are already widely used in newborns for diagnosing diseases at birth. DBS sampling is easy to perform as it requires just a few drops of blood to be collected on a card, potentially allowing parents to take samples at home. In addition, these samples are easy to store and transport, without needing special conditions. This method has recently been applied to measure levels of medicines in blood and our group have been at the forefront of these developments but this approach has not yet been used for MTX. We will find out if we can measure MTX and its products using DBS sampling. The reliability of this method will be determined by using samples from children with JIA and JDM carried out at home.
How will the findings benefit patients?
Applying this approach to methotrexate, for the first time, will be challenging but very worthwhile as it will allow children being treated with MTX to be monitored while remaining at home. Determining MTX product levels using DBS will be of major clinical value as this method could used to monitor MTX therapy in terms of safety, adherence to medication, absorption difficulties and long-term response in children with arthritis.