Background/Purpose: Increasing body of evidence suggest that alarmins such as S100A8/A9 proteins play a critical role in Rheumatoid Arthritis pathogenesis (RA). We aimed to analyze the association between baseline S100A8/A9 protein plasma levels and radiological progression during the first 36 months of early RA.

Methods: Patients fulfilling the ACR/EULAR criteria in the early arthritis cohort ESPOIR were included in this study. S100A8/A9 (also known as calprotectin) levels were assessed in 813 patients of the early arthritis cohort ESPOIR at baseline. Total Sharp-van der Heijde score was assessed at baseline, year 1, 2 and 3. Univariate Cox regressions were used to evaluate the role of the risks factors to detect total Sharp-van der Heijde score progression ≥ 5 points /year. A multivariate risk model, comprising gender, age, baseline CRP,  baseline ACPA, baseline smoking status, baseline DAS28, baseline S100A8/A9 level and treatment with biologic or synthetic DMARD , was constructed using a backward stepwise Cox model. A patient was considered under DMARD treatment when receiving methotrexate≥7.5mg/sem, sulfasalazine, leflunomide or any biological treatment at least 6 months before radiological assessment.

Results: A total of 614 patients were included and analyzed out of 813 patients of the cohort. Significant differences were found between patients with or without radiological progression, in the univariate Cox model : progressors were more likely to be ACPA positive, to be treated biologic or synthetic DMARD and to display high level of baseline CRP and S100A8/A9 proteins (table). In the multivariate analysis, S100A8/A9 level was the only predictor of the structural evolution over 3 years, independently of usual marker of inflammation (Hazard ratio 1.06, 95%CI [1.00-1.11], p=0,045).           .

Conclusion: These results confirm that S100A8/A9 predicts radiological progression, in a large cohort of early rheumatoid arthritis. The correlation between this new biomarker and radiological progression was moderate but independent from other risk factors.