Background Early RA diagnosis and timely treatment can improve patient outcomes. Markers are needed to identify patients with early disease who are at high-risk of joint damage progression. Current clinical and serological variables only explain approximately 32% of the risk1, underscoring the need for new disease specific markers that add to the rheumatologist's prognostic armamentarium. 14-3-3η is a mechanistic, joint-derived, serological marker that potently induces cytokines and joint damage factors, directly implicating it in RA disease pathophysiology.
Objectives The aim of this study was to determine whether 14-3-3η serum levels are predictive of joint damage progression in this recent-onset polyarthritis cohort.
Methods Serum 14-3-3η levels were measured at baseline in 33 patients with recent-onset polyarthritis (EPA) from the Sherbrooke EUPA cohort. Patients were rapidly treated with conventional DMARDs to achieve clinical remission; 3 also received biologic agents. Radiographic progression was defined as a change in Sharp/van der Heijde score (ΔSHS) ≥1 at 30 months. Differences in median 14-3-3η between progressors and non-progressors were analyzed by 2-tailed Mann-Whitney U-test. The relationship between serum 14-3-3η and radiographic progression was investigated by univariate analysis using 14-3-3η cut-offs selected as follows: the manufacturer's (Augurex 14-3-3η ELISA) reported diagnostic cut-off ≥0.19 ng/ml and 2X that,0.40 ng/ml. Stepwise multivariate analyses were performed to determine 14-3-3η's contribution to predicting joint damage progression amongst other clinical and serological variables, including titres of 14-3-3η, RF, CCP, CRP, ESR, together with age, gender and disease duration.
Results Median age was 51 years and 70% were female. Twenty of the 33 (61%) patients progressed after 30 months while 13 did not. Progressors had a median (IQR) ΔSHS of 7.0 (3.3-12.8). 14-3-3η and RF median (IQR) levels at baseline were significantly higher in progressors than non-progressors [2.7ng/ml (0.1-15.9) vs. 0.1ng/ml (0.1–0.2), p=0.006] and [160 IU/ml (40-320) vs. 0 IU/ml (0–160), p=0.006]. Univariate analyses revealed that RF positivity was associated with radiographic progression; relative risk (RR) of 2.8 (95%CI: 1.1-7.6), p=0.035. 14-3-3η, at both cut-offs, was also associated with radiographic progression; ≥0.19 ng/ml, RR=2.0 (1.1-3.7), p=0.02; ≥0.40 ng/ml, and RR=2.2 (1.2-4.1), p=0.006, respectively. 14-3-3η titres were associated with joint damage progression, LR of 5.2, p=0.02. Stepwise multivariate analysis returned 14-3-3η titres (LR=5.6, p=0.02), ESR (LR=6.4, p=0.01), CRP (LR=4.6, p=0.03) and gender (LR=4.4, p=0.04) as independent predictors of radiographic progression, together informing 29.4% of the total variance (R2) in radiographic progression. When 14-3-3η titres were excluded, the R2 for ESR, CRP and gender was 16.8%, indicating that of the 4 significant variables, 14-3-3η accounted for 43% (12.6%/29.4%) of the model's predictive power.
Conclusions Serum 14-3-3η in recent-onset polyarthritis was associated with an increased risk of joint damage progression at 30 months. When added to current prognostic markers, is 14-3-3η an independent predictor of radiographic progression adding 43% to their prognostic predictive power.
de Rooy DPC et al. Rheum. 2011. 50:93.
Disclosure of Interest G. Boire: None declared, N. Carrier: None declared, A. de Brum-Fernandes: None declared, P. Liang: None declared, A. Masetto: None declared, Y. Gui Employee of: Augurex Life Sciences Corp, M. Murphy Employee of: Augurex Life Sciences Corp, W. Maksymowych Consultant for: Augurex Life Sciences Corp, A. Marotta Employee of: Augurex Life Sciences Corp