SAT0082 ASSOCIATIONS OF BASELINE CLINICAL AND BIOMARKER FACTORS WITH SYMPTOMS AND FUTURE DEVELOPMENT OF CLINICALLY-APPARENT RHEUMATOID ARTHRITIS IN AN ACPA POSITIVE COHORT
Authors: Kevin D. Deane, Sunil Nagpal, Navin Rao, Frederic Baribaud, George Vratsanos, Eddie A. James, Jane H. Buckner, Gary S. Firestein, David L. Boyle, Sylvia Posso, William H. Robinson, Laurie K. Moss, Saman Barzideh, Kristen Polinski, Sergei Ivanov, Jennifer Seifert, V. Michael Holers
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Subjects who are in the preclinical rheumatoid arthritis (RA) state can be identified through serum elevations of circulating RA-related autoantibodies, including rheumatoid factor (RF) and antibodies to citrullinated protein antigens (ACPA), prior to the clinical appearance of inflammatory arthritis (IA) and RA. Studying Preclinical RA may identify factors and pathways in disease development, and help to identify therapeutic targets for prevention. Furthermore, trials in ACPA+ subjects have been completed or are underway with the primary goal to prevent future IA/RA. However, relatively few individuals have been studied through the evolution of the Preclinical ACPA+ state to Classified RA. As such there are still many gaps in the understanding of the clinical and immunologic evolution from Preclinical to Classified RA. <h3>Objectives</h3> The study objective is to identify the clinical, environmental and immunologic factors/pathways that are associated with incident IA/RA development in individuals with serum ACPA elevations. <h3>Methods</h3> We created a cohort of 86 ACPA+ subjects who at their baseline study visit did not have a historical or examination (66/68 count) evidence of IA/RA. ACPA+ was defined as a serum elevation of anti-CCP3 (IgG, Inova) on ≥2 occasions above the established cut-off (≥20 units). These subjects were recruited over 18 months through community health-fair screening, ACPA testing of first-degree relatives of patients with RA, and rheumatology clinics. Clinical, environmental and biomarker factors, including RF IgA and IgM [Inova] and high-sensitivity C-reactive protein [hsCRP], were assessed at the baseline visit. Herein we present interim analyses of baseline visits on the whole ACPA+ cohort and longitudinal follow-up on a subset of subjects, with a specific focus on factors that are associated with baseline symptoms and subsequent incident IA/RA. <h3>Results</h3> At baseline, the 86 ACPA+ subjects were a mean age of 58, 66% female, 82% were Caucasian, and 40% self-reported no joint pain, morning stiffness or fatigue. hsCRP positivity (&gt;3 mg/L) was associated with increased rates of self-reported fatigue of &gt;0 on VAS (20% vs. 41%, p=0.04). Ever smoking was associated with increased rates of self-reported morning joint stiffness (18% vs 50%, p≤0.01). In addition, in analyses of longitudinal follow-up data available to date, 10/86 subjects (12%) developed IA classified as RA (2010) a median of 293 days after baseline visit. At baseline, individuals with incident RA exhibited a higher BMI compared to those who did not (27 vs. 32, p=0.03). In addition, positivity for hsCRP and RF, and higher median anti-CCP3 levels, were present in those who developed incident IA/RA although not statistically significant. <h3>Conclusion</h3> Within this new cohort of prospectively followed ACPA+ individuals, smoking and an elevated hsCRP are associated with clinical symptoms of stiffness and fatigue, respectively. The relationship of stiffness and smoking suggests this factor is related to early joint symptoms, and the association of high BMI with incident RA may indicate this is a modifiable risk factor for RA (de Hair 2013). This prospective study will continue, with further study of the factors/pathways that may influence well-being in ACPA+ individuals as well as may influence predictive of or causally linked to the future IA/RA. <h3>Disclosure of Interests</h3> Kevin D. Deane Grant/research support from: Janssen, Consultant for: Janssen, Sunil Nagpal Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Navin Rao Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Frederic Baribaud Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, George Vratsanos Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research and Development, LLC, Eddie A. James Grant/research support from: Janssen, Jane H. Buckner Grant/research support from: Janssen, Gary S. Firestein Grant/research support from: Janssen, David L. Boyle Grant/research support from: Janssen, Sylvia Posso Grant/research support from: Janssen, William H. Robinson Grant/research support from: Janssen, Laurie K. Moss Grant/research support from: Janssen, Saman Barzideh Grant/research support from: Janssen, Kristen Polinski Grant/research support from: Janssen, Sergei Ivanov: None declared, Jennifer Seifert Grant/research support from: Janssen, V. Michael Holers Grant/research support from: Janssen, Consultant for: Janssen