FRI0002 Lower Levels of 14-3-3Eta PREDICT DMARD Associated DAS Remission at 1 Year Follow Up
Authors: D. van Schaardenburg, W.P. Maksymowych, A. Marotta
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Serum 14-3-3η is an RA diagnostic marker whose higher levels are associated with more severe disease. Extracelluar 14-3-3η has been reported to upregulate factors intimately linked to RA pathogenesis. Predictive biomarkers of RA therapy response are needed to assist with clinical management. <h3>Objectives</h3> This study sought to examine the relationship between 14-3-3η serum expression and DMARD remission at year 1 in an early RA cohort. <h3>Methods</h3> Serum 14-3-3η levels were measured in a cohort of 409 early RA patients; all patients were DMARD naïve at baseline and DAS at year 1 was available in 401 patients. Median patient age was 56 years and 73% were female. Response was defined by DAS remission at year 1, DAS-ESR&lt;2.6. The relationship between serum 14-3-3η and response was investigated by univariate analysis using three 14-3-3η concentration cut-offs which were selected as follows: the reported manufacturer9s (Augurex 14-3-3η ELISA) reference range ≥0.19 ng/ml as well as 2 and 4 times that level, namely ≥0.40 and ≥0.80 ng/ml. 14-3-3η9s contribution to predicting response was analyzed by regression analysis controlling for baseline DAS. Multivariate stepwise regression assessed 14-3-3η positivity together with baseline DAS, disease duration, age and gender to identify independent predictors of remission. <h3>Results</h3> At baseline, 67% (n=275) of the early RA patients were 14-3-3η positive using the 0.19 ng/ml cut-off. At a cut-off of 0.40 and ≥0.80 ng/ml, 229 (56%) and 288 (46%) of the patients were positive for 14-3-3η. After 1 year, 130 (32%) of 401 patients achieved DAS remission. Patients who achieved DAS remission had higher median (IQR) baseline DAS, [5.3 (4.5-6.2) vs 4.7 (3.9-5.7), p=0.0005] TJC28 [7 (3-10) vs 4 (2-8), p=0.0006], patient global assessment [56 (38-74) vs 50 (36-65), p=0.013] and ESR [32 (17-48) vs 25 (13-40), p=0.0027]. Fisher exact testing revealed that patients who were negative for 14-3-3η at either the ≥0.4 or the ≥0.8 ng/ml cut-points had a higher likelihood of (LR) and odds (OR) of achieving DAS remission: LR=3.4 p=0.0407, OR=1.5 (95%CI 1.0-2.3) and LR=4.0 p=0.0290, OR=1.5 (95%CI 1.0-2.4), respectively. Regression analysis accounting for baseline DAS further confirmed that those patients who are negative for 14-3-3η9s based on either ≥0.4 or the ≥0.8 ng/ml cut-points are more likely to achieve remission: LR=4.2 p=0.04 and LR=4.9 p=0.03. Independent predictors of DAS remission as determined by stepwise multivariate analysis were baseline DAS (LR=12.0 p=0.005), 14-3-3η negativity (LR=5.6 p=0.02), and male gender (LR=8.5 p=0.004). <h3>Conclusions</h3> 14-3-3η is a mechanistic biomarker that is believed to play a role in the pathogenesis of RA. This study demonstrates that early RA patients with 14-3-3η levels below 0.8 ng/ml are more likely to achieve DAS remission at year 1 in response to DMARD therapy. This may be in part explained by in vitro observations which demonstrates that 14-3-3η behaves as a more potent ligand with increasing concentrations that are well within the clinical biomarker expression range. Further studies are warranted to determine if this is a general phenomenon across all classes of therapy. <h3>Disclosure of Interest</h3> D. van Schaardenburg: None declared, W. Maksymowych Consultant for: Augurex Life Sciences Corp, A. Marotta Employee of: Augurex Life Sciences Corp <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4515