Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation which may lead to irreversible joint damage, reduced mobility and decreased quality of life. Although clinical remission can often be achieved with DMARD therapy, remission is often not observed on imaging and the presence of bone edema on MRI is the current best predictor of radiographic progression. Another marker associated with radiographic outcomes is 14–3-3η, which is a joint-derived protein whose serological expression is independent of CRP1, modifiable over time2, and linked with the upregulation of factors that drive the joint damage process3.
Objectives Examine whether patients who achieve clinical remission at year 1 (Yr1) but remain 14–3-3η positive have worse radiographic outcomes by year 3 (Yr3).
Methods Baseline (BL) and Yr1 plasma 14–3-3η protein titres were measured in a cohort of 360 early RA patients from the Reade Institute; all patients were treatment naïve at BL. 14–3-3η positivity was based on the cut-off ≥0.19 ng/ml. Mean (SD) patient age was 55 (12) years and 74% were female. Radiographic progression at Yr3, across the whole cohort and in those patients that achieved Yr1 DAS28 ESR remission (<2.6), was assessed as well as ΔSHS of ≥1, 3 and 5 points from Yr1 to Yr3. Mann-Whitney and Fisher Exact testing was performed to determine the significance (p≤0.05) of group differences and the association with marker positivity, respectively.
Results At BL and Yr1, 245 (68%) and 210 (58%) of patients were 14–3-3η positive. Patients who were positive at baseline or Yr1 had significantly worse radiographic progression by Yr3 than 14–3-3η negative patients; BL 14–3-3η positivity (+ve vs.-ve): [2.0 (0.0–7.5) vs. 0.0 (0.0–4.0), p=0.019] and Yr1 14–3-3η positivity (+ve vs. -ve): [2.0 (0.0–8.0) vs. 0.0 (0.0–4.0), p=0.0012]. A total of 109 (30%) patients achieved Yr1 DAS28 remission. Patients who achieved remission yet were 14–3-3η positive at Yr1 experienced significantly worse radiographic progression by Yr3 than negative patients [1.0 (0.0 -5.0) vs. 0.0 (0.0–2.0), p=0.016]. A similar and significant trend for radiographic progression was observed in patients who did not achieve clinical remission and were 14–3-3η positive at Yr1 versus those who were 14–3-3η negative [2.0 (0.0–11.0) vs. 1.0 (0.0–5.0), p=0.029]. The table below demonstrates that positivity for 14–3-3η at both BL and Yr1, across the whole cohort as well as in those achieving clinical remission, is associated with radiographic progression. Yr1 positivity was more strongly associated with ΔSHS ≥5 than BL.
Conclusions Patients who achieve DAS28 remission at Yr1 but remain 14–3-3η positive are at risk of future radiographic progression. As expected with a modifiable biomarker such as 14–3-3η, serial assessment is more informative than baseline assessment.
Ann Rheum Dis 2013;72(Suppl 3):592;
Arthritis Rheum. 2011. 63 (Suppl 10):428;
Arthritis Res Ther 2014,16.2:R99.
Disclosure of Interest D. van Schaardenburg Consultant for: Augurex Life Sciences Corp., S. Turk: 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)