Measuring the levels of a specific protein in the blood before starting treatment with disease-modifying anti-rheumatic drugs may help predict patients’ response to therapy, according to a recent study published in The Journal of Rheumatology.
Managing the symptoms of juvenile idiopathic arthritis (JIA, called “idiopathic” because it has an unknown cause and often shortened to just juvenile arthritis), often requires the use of disease-modifying anti-rheumatic drugs (DMARDs). These include methotrexate (MTX) or biologic agents like Enbrel (etanercept) and Humira (adalimumab), commonly known as anti-tumor necrosis factor (TNF) therapy.
Despite the effectiveness demonstrated by these therapies, up to 40 percent of patients do not achieve good treatment outcomes, highlighting the need for efficient biomarkers that may help predict patients’ responses.
Researchers evaluated whether measuring blood levels of the protein S100A12 could be a suitable predictor for treatment outcomes in JIA patients.
S100A12 is a granulocyte-specific S100 pro-inflammatory protein and has been validated as a predictor of relapse risk and disease activity in juvenile arthritis. However, little is known about its predictive potential in response to therapy.
In the study, “S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis,” the team analyzed clinical data collected from three groups of patients: the UK Childhood Arthritis Response to Medication Study (CHARMS), the Dutch Arthritis and Biologicals in Children (ABC) Register, and the German Registry for Biologics in Paediatric Rheumatology (BIKeR).
A total of 163 patients diagnosed with JIA were included in the analysis, of whom 75 were treated with methotrexate (MTX) and 88 were treated with anti-TNF alone or in combination with other drugs, such as prednisolone. Of note, most (74) patients in the anti-TNF therapy group were also receiving MTX.
The team found that when compared to non-responders, patients who responded to the administrated therapies, either anti-TNF or MTX, had significantly higher baseline levels of blood S100A12.
In 88 of the patients, of whom 64 responded to therapy, it was possible to measure S100A12 levels upon treatment initiation, revealing that at follow-up, responders had significantly lower amounts of S100A12 protein compared to baseline levels.
Also, treatment with additional drugs other than MTX or anti-TNF did not change the association found between S100A12 levels and the response to therapy.
These results showed that responders to methotrexate or anti-TNF treatment can be identified by higher pretreatment S100A12 serum concentration levels.
However, it is likely that no single biomarker will be sensitive or specific enough to predict treatment response and as such, the use of multimarker panels could prove to be a more suitable approach.
Although more studies are necessary, S100A12 should be considered as a valuable tool to be added to these predictive models, researchers said.
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