Background Achievement of radiographic remission in RA is dependent on early patient identification and effective triaging to enable prompt referral to enable tight control treatment strategies. Assessment within 12 weeks of symptom onset i.e. the “window of opportunity” is reportedly associated with less joint destruction and a higher likelihood of achieving remission. Based on RF or anti-CCP2 testing at the primary care level, approximately one half of early RA patients may test negative and not be referred. Further, since referral times can often be lengthy, rheumatologists in consult with GPs require more sensitive, disease specific tools to prioritize the referral of patients who are at greatest risk for radiographic progression. 14–3-3η is a soluble diagnostic RA marker that is involved in the pathophysiology of the disease and informs joint damage progression.

Objectives The aim of this study was to examine the combined benefit of 14–3-3η and anti-CCP2 testing in early undifferentiated polyarthritis to inform radiographic progression rate.

Methods Serum 14–3–3η levels were measured at baseline in 331 patients with recent onset polyarthritis (Sherbrooke EUPA), for which a follow up of at least 60 months was completed. Mean (SD) age was 60 years, 62% were female, and median (IQR) duration of symptoms was 4 (1.7–5.7) months. Radiographic progression was defined as a change in Sharp/van der Heijde score, ΔSHS≥1 at 18, 30, 42, and 60 months. Differences in mean ΔSHS based on 14 -3-3η positivity was assessed using the Mann-Whitney U-test at the diagnostic cut-off of ≥0.19 ng/ml. ANOVA analysis was performed to assess the significance of 14–3-3η and anti-CCP2 co-expression with radiographic progression over 60 months.

Results At baseline, 46% and 40% of patients were positive for 14–3-3η and anti-CCP2, respectively. Together, 14–3-3η or anti-CCP2 captured 55% of patients. Of these, 58% were positive for both markers whereas 42% were positive for one or the other. Over the course of 60 months, mean (SD) radiographic progression from baseline was significantly higher in 14–3-3η seropositive patients when compared with seronegative patients, 10.0 (15.6) vs. 6.3 (13.40) p=0.022. Radiographic progression based on biomarker co-expression analysis shows that patients who were positive for both anti-CCP2 and 14–3-3η had the most significant changes in radiographic outcomes over 60 months.

Conclusions Early undifferentiated polyarthritis patients who are positive for 14–3-3η and anti-CCP2 have more radiographic progression over 60 months. 14–3-3η positive status can assist with prioritization of high joint damage risk patient referrals to rheumatologists.

1. de Rooy DPC et al. Rheum. 2011. 50:93.

Disclosure of Interest G. Boire Grant/research support from: The 14–3-3eta measurements were performed free of charge by Augurex, Augurex remaining totally blinded to clinical data. All the analyzes were performed in Sherbrooke without sharing of clinical data of individual patients with Augurex personnel., 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., J. Savill Employee of: Augurex Life Sciences Corp., S. Michienzi Employee of: Augurex Life Sciences Corp., H. Menard: None declared, W. Maksymowych Consultant for: Augurex Life Sciences Corp., (Co-inventor of 14–3-3η), A. Marotta Employee of: Augurex Life Sciences Corp., (Co-inventor of 14–3-3η)