FRI0031 OBSERVATIONS ON BIOMARKERS IN VERY EARLY RHEUMATOID ARTHRITIS CONSECUTIVELY RECRUITED OVER 20 YEARS, FROM BASELINE PRESENTATION TO FIVE-YEAR OUTCOMES
Authors: N. Carrier, S. Roux, A. Masetto, A. J. Debrum Fernandes, P. Liang, M. Maoui, G. Boire
Journal: Annals of the Rheumatic Diseases (2020)

Background: Since July 1998, the Early Undifferentiated PolyArthritis (EUPA) cohort recruited consecutive adults with recent-onset immune-mediated polyarthritis 1,2 . Patients were treated aiming at 0 swollen joint. Objectives: To analyze the impact of biomarkers over 20 years on baseline variables, treatments, comorbidities and outcomes over the first 5 years of follow up. Methods: Variables and Outcomes were collected over 5 years in consecutive patients fulfilling RA criteria, grouped according to date of inclusion (Period 1: 1998-2004; Period 2: 2005-2010; Period 3: 2011-2018). Comparisons of baseline characteristics, treatment, and outcomes over 5 years between the 3 Periods were previously presented (ACR 2018 and 2019). Erosive damage was scored according to Sharp/van der Heijde; erosive status was defined as ≥5 Erosion units. We now present observed associations between the presence of baseline prognostic biomarkers (anti-CCP2 (ACPA), RF, anti-Sa, and erosive status) with concomitant and subsequent disease activity levels, radiographic scores, comorbidities and impact of treatment. False discovery rate correction was used to adjust p-values for multiple comparisons. Results: 753 patients were included: 247, 263 and 243 in Periods 1, 2 and 3, respectively. Variables at baseline. No biomarkers, including erosive status, were associated with demographics or disease activity. Erosive disease was more prevalent in ACPA+ (19.9% vs 13.9%, p=0.0417). Current smoking decreased by period (20.6, 17.2, 8.6%; p=0.02) in ACPA negatives only, remaining stable among ACPA+ (25.3, 20.9, 18.8%, NS). All comorbidities were significantly more present in ACPA negatives vs positives (RR between 1.55 and 1.99). Prevalence of cardiovascular (CV; 44.8, 55.0, 60.0%; p=0.036) and cancer (4.1, 7.1, 13.1%; p=0.02) comorbidities increased over time in ACPA negatives and remained stable in ACPA+ (CV: 33.0, 30.8, 40.7, NS; cancer: 3.0, 4.4, 6.2, NS). RF positivity decreased by period (47.8, 36.9, 36.7%, p=0.03), but ACPA+ remained stable (40.8, 35, 35.4% NS). Outcomes over 5 years of follow up. There was no link between the presence of any biomarker and subsequent disease activity scores. Positive ACPA, RF and anti-Sa at baseline predicted development of more erosive status (RR = 1.50; 1.37 and 1.52, all p&lt;0.001). 68% reached DAS28 remission overall (70.3% in ACPA negatives, 65.2% in ACPA+). Independent of ACPA status, remission rates increased between Periods 1 vs 2 (RR = 1.14, p=0.04) and 1 vs 3 (RR=1.13, p=0.055), but not between 2 vs 3. CV comorbidities among ACPA+ increased significantly more over time vs ACPA negatives (+8.9% vs +4.1%; RR = 1.18, p=0.03). Erosion scores increased significantly more in ACPA+ treated with DMARDs only vs receiving a biologic (ΔSharp: 3.98 vs 3.11, p= 0.026; ΔErosions: 2.58 vs 1.83, p= 0.02). By period, erosive status decreased significantly (Periods 2 vs 1: RR= 0.65, p=0.002; 3 vs 1: RR=0.42, p=0.002; 3 vs 2: RR=0.64, p=0.007), both in ACPA+ and negatives. Conclusion: In this cohort of recent onset RA recruited over 20 years, we observed a constant drift towards RF-negative arthritis at baseline with decreasing smoking rates and increasing comorbidities in seronegative patients. Positive antibodies were associated more cardiovascular comorbidities accrual. Autoantibody positive (especially ACPA+) patients developed more erosive disease and had better erosion outcomes with biologic treatments. Irrespective of the presence or absence of biomarkers, marked improvements in control of disease activity and in remission rates occured over each period. References: [1]Boire G, et al. Arthritis Res Ther 2005;7:R592-R603; [2]Carrier N, et al . Arthritis Res Ther 2016; 18 :37 Disclosure of Interests: Nathalie Carrier: None declared, Sophie Roux: None declared, Ariel Masetto: None declared, Artur J. deBrum Fernandes: None declared, Patrick Liang: None declared, Meryem Maoui Employee of: Bristol Myers Squibb Canada, Gilles Boire Grant/research support from: Merck Canada (Registry of biologices, Improvement of comorbidity surveillance) Amgen Canada (CATCH, clinical nurse) Abbvie (CATCH, clinical nurse) Pfizer (CATCH, Registry of biologics, Clinical nurse) Hoffman-LaRoche (CATCH) UCB Canada (CATCH, Clinical nurse) BMS (CATCH, Clinical nurse, Observational Study Protocol IM101664. SEROPOSITIVITY IN A LARGE CANADIAN OBSERVATIONAL COHORT) Janssen (CATCH) Celgene (Clinical nurse) Eli Lilly (Registry of biologics, Clinical nurse), Consultant of: Eli Lilly, Janssen, Novartis, Pfizer, Speakers bureau: Merck, BMS, Pfizer