The potency of cell-based assays to predict response to TNF inhibitor therapy

Tumor necrosis factor inhibitors (TNFi) have revolutionized rheumatic and inflammatory diseases therapy. Despite their efficacy, at least 30% of patients do not respond to TNFi therapy. There are five FDA-approved TNFis and several TNFi biosimilars, which are equivalent to their reference drugs. Although all TNFi drugs neutralize the TNF cytokine, they differ in many structural and pharmacokinetic properties. These differences may lead to varying patient responses, making one TNFi, but not another, effective for a given patient. An accurate prediction of a priori responsiveness to therapy, rather than trial and error, would therefore be of great value. Biomarkers that may guide the optimal TNFi choice are an unmet need. The authors discuss the diagnostic and predictive utilities ofCell-Based Assays (CBAs) for individualized TNFi therapy selection based upon a given patient's immune cell response to the various TNFi drugs to predict the clinical outcomes to those drugs. CBAs allow to assess response to multiple TNFi drugs simultaneously by measurement of biomarkers that could distinguish between TNFi responders and non-responders, effectively prioritizing the TNFi of choice. This literature search focuses upon biomarkers and techniques that could be used as predictive CBAs for clinical response to TNFi.