Metabolomic Markers of Disease Activity and Therapeutic Response in Autoimmune Arthritis
Autoimmune arthritis, in the form of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), is the most common rheumatic condition worldwide. It manifests as chronic joint inflammation that results in significant morbidity and disability associated with irreversible joint damage.
Methotrexate (MTX) continues to be the most widely used drug in the treatment of autoimmune arthritis and is effective in modifying the underlying disease process and preventing disease progression. However, MTX therapy is characterized by a slow onset of action and an unpredictable response profile that results in therapeutic failure in approximately one out of every three patients treated. As a result, the treatment of RA and JIA frequently requires individual tailoring of drug therapy and is characterized by a trial-and-error approach to therapy that results in a significant delay in effective disease control.
Recognizing that early control of disease activity is among the strongest positive predictors of long-term outcomes, there remains a critical need to identify biomarkers to guide clinicians in the early selection and optimization of drug therapy in the treatment of these patients.
Our goal is to apply a translational metabolomics approach to identify molecular biomarkers of disease activity and MTX response in autoimmune arthritis, towards a precision medicine-based approach to the treatment of autoimmune arthritis. In this work we hypothesize that autoimmune arthritis results in metabolic dysregulation with corresponding changes in metabolomic profiles that are associated with response to MTX, which therefore represent molecular markers that can be utilized to guide therapy in these patients. To test this hypothesis, we will utilize patient samples in combination with advanced techniques in metabolomics and biomarker assay development to address the following aims:
- identify circulating metabolomic markers of disease in autoimmune arthritis,
- identify circulating metabolomic markers of MTX response in autoimmune arthritis, and
- develop a chip-based assay for the quantitation of molecular markers of MTX response in autoimmune arthritis.
Ryan S. Funk, PharmD, Ph.D.
Assistant Professor, Pharmacy Practice, University of Kansas
Junior Assistant Professor, Department of Pharmacology, Toxicology & Therapeutics, University of Kansas School of Medicine
Junior Faculty, Kansas Institute for Precision Medicine COBRE
Ryan Funk's NCBI Bibliography