Not so long ago, a diagnosis of juvenile arthritis meant treatment with aspirin – lots of aspirin – and sometimes corticosteroid tablets and injections. Then came new and improved drug options.
As treatment options have increased, treating the disease has moved from a one-size-fits-all approach to one largely of trial and error. What’s next? Personalized medicine, say experts.
Personalized medicine is treatment targeted to that individual child, based on factors specific to the child and her disease. “There is no question certain medications work better for certain types of JA,” says Richard K. Vehe, MD, director of the division of pediatric rheumatology at the University of Minnesota.
For example, anakinra (Kineret) and canakinumab (Ilaris) work well for systemic JIA, but not well for other types, Dr.Vehe says. Etanercept (Enbrel) works well for oligoarthritis and polyarticular. For oligoarthritis and polyarticular arthritis with eye involvement, adalimumb (Humira) seems to have an advantage. “However, there are still exceptions, and that is where medications can really be tailored,” he says. “A time is coming when we might ‘profile’ a patient’s biology to select the right treatment.”
As well as enabling doctors to select the most effective treatment for a particular child, profiling biology may help them determine if a child is likely to suffer medication side effects, and when – and if – a medication can be stopped without causing a flare.
The concept of personalized medicine recognizes that there are probably far more than the known basic subtypes of JIA – and that different subtypes may respond better to different treatments.
Scientists are working to tease apart these subtypes with gene expression technology, which allows them to examine the products of thousands of different genes at the same time and compare patterns from one child to another. This work is leading to some interesting findings that could eventually enable doctors to target more aggressive treatment to children at risk of more severe arthritis, says Robert A. Colbert, MD, PhD, chief of the pediatric translational research branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
In the first of two new, related studies supported in part by the Arthritis Foundation and NIAMS, scientists at Cincinnati Children’s Hospital Medical Center showed that gene expression technology could be used to accurately identify the major known subtypes of JIA. In the second study, they looked more closely at patients from the study with polyarticular JIA and found patterns that indicated at least three subgroups of that subtype.
Dr. Colbert says the new findings take pediatric rheumatologists a step closer to more precisely classifying JIA. “If we know exactly what a patient has we have a better idea of knowing whether it is going to be a severe arthritis and how to treat them,” he says.
Minimizing Treatment Risks
Other scientists are looking at markers in the blood of individuals that can predict risk for medication side effects. One of the mostly widely studied drugs in this regard – as well as one of the most successful and widely used drugs for juvenile arthritis – is methotrexate. For some children, as well as adults, adverse effects make it necessary to stop the drug.
The reason, researchers have found, may be genetic mutations that interfere with the ability to metabolize the B vitamin folate.
Researchers are looking for other genetic variations which would better predict who would be most likely to suffer side effects and thus might not be appropriate candidates for methotrexate therapy.
Knowing When to Say When
Once doctors find the right treatment for a child, the next questions are: How do we know when arthritis is under control? How long must the child take the medication? Will stopping medication cause the disease to flare?
In research supported by the Arthritis Foundation and led by James N. Jarvis, MD, at the Oklahoma University Health Services Center, researchers used genetic profiling to look for evidence of JIA remission. They found underlying abnormalities in gene expression are still present, even if such abnormalities are not reflected in standard clinical measures such as the sed rate, the C-reactive protein (CRP) level or white blood cell count. Rather than a resolution of the underlying inflammatory process, they say remission is more likely to be the result of a balance between pro-inflammatory and anti-inflammatory mechanisms, and a disruption of that balance can cause disease to flare. Further research is needed to determine the factors that disrupt the balance and to determine when and if children can discontinue or taper medication without experiencing a disease flare.
The ability to design treatment plans to achieve the best outcomes for children with arthritis is one of the top goals for the Arthritis Foundation’s research program.
As a part of this goal, the Foundation has long advocated the establishment of a pediatric rheumatology registry, which Dr. Vehe says would be a crucial step toward personalized medicine.
“While a better understanding of the different types of JIA is already helping doctors select the most effective treatment by disease type, a database of tissues samples, medication histories, side effect histories and efficacy data would enable research that would help us to develop new ways to select appropriate treatments for each individual child with JIA,” says Dr. Vehe.
In the meantime, researchers are already making strides in developing new therapies and better classifying the forms of juvenile arthritis and factors that affect treatment response – either good or bad – so that, one day, a sample of blood may be all it takes to get each child the most effective treatment with the least risk of unwanted side effects.