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SAT0037 14-3-3 ETA Sero-Positivity Marks More Severe Disease and Titres Inform Response to Therapy, also in Patients with Lower Crp

Background There is an unmet need for RA markers that inform prognosis and treatment response. While RF and anti-CCP are useful, augmenting their predictive capacity with additional markers is desirable. CRP is routinely used to gauge response to therapy but remains low in a proportion of patients, limiting its clinical utility in that subgroup. 14-3-3eta, a soluble RA diagnostic marker, is involved in the disease process, complements RF and anti-CCP and is modifiable with anti-TNF therapy in RA and PsA. Objectives We examined whether positive serum 14-3-3eta corresponds with RA disease profile, and whether baseline titres inform response to anti-TNF therapy, also in patients with a lower CRP. Methods Serum 14-3-3eta was measured in banked samples of 112 patients with established RA (N=75; RAPPORT cohort) and early disease (N=37; TEACH and I-COBRA cohorts). Patients were biologically-naïve, median age 57 and 76% female. 14-3-3eta was considered +ve at >0.19 ng/ml and median differences in clinical variables between 14-3-3 eta +ve and -ve groups were evaluated using the Mann-Whitney U-test. For relationships between the clinical variables and 14-3-3eta, Pearson correlations were run. The 75 established RA patients were candidates for anti-TNF therapy and 14-3-3eta serum concentrations were additionally measured at ~15 weeks post-treatment. EULAR criteria were used to define Good response. Across the group and in patients with a low CRP (≤10mg/L), the significance of median differences in 14-3-3eta expression between Good EULAR responders and non-responders was evaluated using the Mann-Whitney U-test. A ROC curve and corresponding AUC was generated. Results Of the 112 patients, 92 (82%) were 14-3-3 eta +ve and 20 (18%) were -ve. In the 14-3-3eta +ve vs -ve group the following medians were significantly higher; HAQ (1.9 vs 1.0, p=0.001), ESR (40.5 vs 25.0mm/hr, p=0.007), CRP (18.8 vs 6.6mg/l, p=0.018) and anti-CCP (54.6 vs 5.0U/ml), p=0.02); while DAS28 (6.7 vs 6.0, p=0.16) and RF (12.0 vs 8.0IU/ml, p=0.12) showed only a trend. No significant Pearson correlations emerged between any of the baseline variables and 14-3-3eta titres, especially CRP. Of the 75 established RA patients receiving anti-TNFs, 15 (20%) achieved a Good EULAR response and had significantly lower median baseline 14-3-3eta than those that did not (0.72 vs 2.52ng/ml; p=0.015). Low CRP did not correspond with treatment response and 27 of the 75 patients (36%) had a baseline CRP ≤ 10mg/L; 7 (26%) of which achieved a Good EULAR response and had a lower median 14-3-3 eta than the 20 that did not (0.0ng/ml vs 3.5ng/ml; p=0.0043). The corresponding ROC AUC for response in the low CRP group was 0.88 with an optimal 14-3-3eta cut-off of 0.48ng/ml; LR+ =14.3 and LR- =0.31. Conclusions In RA, 14-3-3eta sero-positivity marks more severe disease and lower titres correspond with better response to anti-TNF therapy, also in patients with lower CRP. Disclosure of Interest W. Maksymowych: None Declared, V. Bykerk: None Declared, K. Siminovitch: None Declared, M. Boers: None Declared, R. Landewé: None Declared, D. van der Heijde: None Declared, P. P. Tak: None Declared, M. Genovese: None Declared, M. Weinblatt: None Declared, E. Keystone: None Declared, K. Young: None Declared, A. Marotta Employee of: Augurex Life Sciences Corp