Serum 14-3-3η As Predictor of Clinical Remission and Progression of Structural Damage in Early Rheumatoid Arthritis Following a Treat-to-target Strategy in a Randomized Controlled Trial.

Objective 14-3-3 eta is a proinflammatory mediator critical to joint destruction in rheumatoid arthritis (RA). We aimed to evaluate serum 14-3-3 eta for predicting disease activity and radiographic progression in patients with early RA in the double-blinded, randomized OPERA trial. Method 180 patients with early RA were randomized to receive methotrexate (MTX) + adalimumab or MTX + placebo in combination with glucocorticoid injections into swollen joints. Disease activity was measured using the 28-joint Disease Activity Score-C-reactive protein (DAS28-CRP). Clinical remission was defined as DAS28-CRP < 2.6. X-rays of hands and feet were evaluated by the Total Sharp van der Heijde score (TSS). Radiographic progression was defined as exceeding the smallest detectable change (1.8 TSS-units). Serum 14-3-3 eta was determined by enzyme-linked immunosorbent assay. Multivariate logistic regression models were used to identify predictors of DAS28-CRP remission at 6 months and radiographic progression at 12 months. Results Baseline 14-3-3 eta was a borderline significant independent predictor of radiographic progression at 12 months (odds radio = 1.02, 95% confidence interval 1.00-1.03, p = 0.05). In anti-cyclic citrullinated peptide antibody (ACPA)-negative patients, a moderate/high baseline 14-3-3 eta concentration increased the risk of radiographic progression at 12 months [4/51 (8%) vs 3/9 (33%), chi 2 = 4.823, p = 0.028]. No value of 14-3-3 eta for predicting achievement of clinical remission was found. Conclusion Serum 14-3-3 eta was a borderline significant predictor of radiographic progression, particularly in ACPA-negative patients, but not of predicting achievement of clinical remission. Optimal cut-off levels of 14-3-3 eta for predicting radiographic progression in RA need further clarification.