to neighboring joints. Taken together, extracellular 14-3-3η upregulates pro-inflammatory factors directly that are targeted with small molecules and/or biological Disease-modifying antirheumatic drug (DMARDs), including TNF, IL-6 and Janus kinases. The table below defines the medicines by target. Key Clinical Findings The body of independent evidence supporting the clinical utility of 14-3-3η continues to expand. As of 2022, there have been over 50 peer-reviewed citations and 200 conference proceedings describing the clinical value of the 14-3-3η biomarker. Diagnostic Value of 14-3-3η Marker. As shown in the table above, a number of studies have evaluated the specificity, sensitivity and value of 14-3-3η in combination with rheumatoid factor (RF) and/or the anti-cyclic citrullinated protein (ACPA, anti-CCP). According to Abdelhafiz et al. meta-analysis of all studies reported a pooled sensitivity of 73% (95% CI: 71 - 75) and a pooled specificity of 88% (95% CI: 87 - 90). In an Early Undifferentiated Polyarthritis (EUPA) cohort from the University of Sherbrooke where 14-3-3n were assessed in 331 subjects, the diagnostic accuracy of RF, CCP and RF and/or CCP was increased by: 24.0%, 36.8% and 15.0% respectively. Prognostic Value of the 14-3-3η Marker. An analysis of 331 patients from the EUPA cohort with five (5) years of longitudinal follow-up demonstrated that baseline 14-3-3η positivity, at the diagnostic cut-off of > 0.19 ng/ml, was associated with more radiographic progression over the five (5) years. Sustained and/or elevated 14-3-3η positivity over the course of the five (5) years of follow-up was associated with a higher likelihood of radiographic progression. Serial decreases in 14-3-3η of 0.76 ng/ml or reversion to a negative test during follow-up was associated with less subsequent radiographic progression. Serial Changes in 14-3-3η Marker with Effective Disease Management. 14-3-3η has been described as a modifiable marker, with post-treatment levels having been reported to decrease, stay the same, or in some cases increase despite patients being treated with different classes of therapy including small molecule and biological DMARDs like Methotrexate, Adalimumab, Tocilizumab, Tofacitinib and Upadacitinib. Post-treatment decreases and/or reversion to a negative 14-3-3η test is typically associated with better patient outcomes, whereas sustained positivity and/or increases in the 14-3-3η marker longitudinally is often associated with worse outcomes. Further research is required to determine if certain therapies have a greater impact on the modifiability of 14-3-3η. Current data points towards more of a proximal or interactive effect between 14-3-3η and TNF alpha. Targeting Drug Free Remission. With the