OP0120 BIOLOGICS MAY PREVENT CARDIOVASCULAR EVENTS IN RHEUMATOID ARTHRITIS BY INHIBITING CORONARY PLAQUE FORMATION AND STABILIZING HIGH-RISK LESIONS
Authors: G. Karpouzas, S. Ormseth, E. Hernandez, M. Budoff
Journal: Annals of the Rheumatic Diseases (2020)

Background: Biologic disease-modifying antirheumatic drugs (bDMARDs) effectively control inflammation and may improve cardiovascular outcomes in Rheumatoid arthritis. Objectives: To evaluate if bDMARDs decrease long-term cardiovascular disease (CVD) risk in rheumatoid arthritis and whether potential benefits might be rendered by impacting coronary plaque formation or progression. Methods: In this single-center observational cohort study, 150 patients underwent computed tomography angiography for evaluation of coronary atherosclerosis (total, non-calcified, mixed/calcified and low-attenuation or high-risk plaque); 101 had repeat assessments within 6.9±0.3 years to evaluate plaque progression. All CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and heart failure hospitalization. The Framingham-D’Agostino score assessed clinical risk. Segment stenosis score (cumulative stenosis) measured plaque burden. The effect of bDMARD treatment on CVD events was assessed using marginal structural models. The inverse probability of treatment and censoring weights were used in a weighted pooled logistic regression with current bDMARD use and time since study entry included in the model to approximate a Cox proportional hazards model allowing for time-varying weights. Robust logistic regression evaluated the effect of bDMARD exposure (&gt;50 percent of follow-up period) on likelihood of new plaque formation or change in plaque composition in per-segment models adjusted for Framingham-D’Agostino score, time between scans, statin duration, cumulative prednisone dose and time-averaged CRP. Results: Sixteen patients incurred 19 CVD events. Current bDMARD use associated with lower CVD risk (OR=0.20 [95%CI=0.05-0.75], p=0.018, Figure 1). However, the effect of bDMARDs was no longer significant when a 6-month exposure extension was applied (OR=0.42 [95% CI 0.13-1.38], p=0.15). The effect of bDMARD use on CVD risk was moderated by non-calcified plaque and low-attenuation plaque presence (Figure 1); specifically, bDMARDs were associated with lower CVD risk only in patients with non-calcified plaque (p=.048) or low-attenuation plaque (p=0.036) at baseline. Per-segment plaque progression analyses showed no main effect of bDMARD exposure on likelihood of new plaque formation (Figure 2). However, bDMARD exposure predicted lower likelihood of new plaque forming in segments without plaque among patients without mixed/calcified plaque in other coronary segments (OR=0.40 [95%CI=0.17-0.93]), but not among those with mixed/calcified plaque elsewhere in their arteries (OR=1.60 [95%CI=0.71-3.62]). Moreover, transition of non-calcified to mixed/calcified plaque associated with bDMARD exposure (OR=4.00 [95%CI=1.05-15.32]). bDMARD use also predicted low-attenuation plaque loss (p=0.042). Figure 1. Effect of bDMARD use on cardiovascular disease risk stratified by coronary plaque presence Figure 2. Effect of bDMARD exposure on plaque formation and transition from baseline to follow-up Conclusion: In rheumatoid arthritis, bDMARD use associated with reduced long-term CVD risk, lower likelihood of new plaque formation in patients with early atherosclerosis, stabilization of high-risk plaque and protective calcification of non-calcified lesions. Disclosure of Interests: George Karpouzas Grant/research support from: Pfizer, Consultant of: Sanofi-Genzyme-Regeneron, Janssen, Speakers bureau: Sanofi-Genzyme-Regeneron, BMS, Sarah Ormseth: None declared, Elizabeth Hernandez: None declared, Matthew Budoff: None declared