TRACKING THROMBOEMBOLIC EVENTS AND ANTIPHOSPHOLIPID SYNDROME FROM ONSET OF SYSTEMIC LUPUS ERYTHEMATOSUS: A POPULATION-BASED STUDY

PV021 / #98 Poster Topic: AS03 - Antiphospholipid Syndrome Background/Purpose Understanding how, when and in whom Antiphospholipid Syndrome (APS) and thromboembolic events (TE) develops in Systemic Lupus Erythematosus (SLE) is important as it may facilitate risk stratification and preventive strategies. Here, we aimed to track patients from SLE diagnosis and assess relationships between APS, TE and antiphospholipid antibodies (aPL) during follow-up. Methods We included all new SLE patients residing in Southeast Norway 2000-2017. All patients had chart review confirmed diagnosis, fulfilled the 2019 European League Against Rheumatism and American College of Rheumatology SLE classification criteria and were captured within 1 year of diagnosis. Follow-up ended 1 January 2018. APS was defined by the 2006 Sydney classification criteria and aPL positivity referred to positive anticardiolipin, anti-b2glycoprotein and/or lupus anticoagulant following international guidelines. TE were defined by both arterial and venous events and included ischemic stroke, transient ischemic attack, myocardial infarction, angina pectoris or syndromes caused by occlusion of major venous vessel identified either by chart review or by ICD-10 code (I20-22, I63, G46, R96, I26, I80-I82) in The National Cause of Death Register. We estimated APS- and TE-free survival using Kaplan-Meier methods and identified factors associated with TE with Cox regression analysis. Results Among 700 new SLE patients, 79 (11%) had co-occurring APS after a mean follow-up of 8 years (SD 5). Compared to non-APS patients, APS patients more frequently had thrombocytopenia (25/79, 32% vs 123/621, 20%, p-value<0.012), neuropsychiatric lupus (6/79, 8% vs 16/621, 3%, p-value<0.016) and anti-dsDNA antibodies (66/79, 84% vs 450/621, 72%, p-value<0.035) at the time of SLE diagnosis, but mean age at SLE diagnosis (37, SD 15 vs 39, SD 17, p-value=0.309) and frequency of LN were the same (29/79, 37% vs 195/621, 31%, p-value=0.341). During follow-up, 54 SLE patient developed a new APS. At the time of SLE diagnosis, 45 of these 54 patients (83%) were aPL positive, 5 (9%) were aPL-negative and 4 (7%) had an unknown aPL status. The 5-year APS-free survival was higher in aPL-negative (0.99, 95% CI 0.97-1.00) than aPL-positive patients (0.80, 95% CI 0.74-0.85, p<0.001). (Figure 1) By the end of follow-up, 156 (22%) patients had experienced at least 1 TE, with a clear clustering around SLE diagnosis. Of the 36 TEs occurring in the same year as SLE diagnosis, 26 (64%) were related to new APS. (Figure 2) Excluding those with TE or APS prior to SLE diagnosis, we found that TE developed in 45/206 (22%) of aPL-positive patients, 31/332 (9%) of aPL-negative patients and in 13/88 (15%) of patients with unknown aPL status at time of SLE diagnosis. Overall, 10-year TE-free survival was 0.84 (95% CI 0.81-0.87). TE-free survival was lower in the aPL-positive patients than in the aPL-negative already 1 year after SLE diagnosis (0.88, 95% CI 0.83-0.92 vs 0.98, 95% CI 0.96-0.99, p-value<0.001). Stratified by age, aPL-negative patients <50 years at diagnosis had persistently high TE-free survival, while patients ≥50 at SLE diagnosis continued to develop TE across the follow-up period, both in aPL-negative and aPL-positive patients. (Figure 2) In multivariable analyses lupus anticoagulant, ≥2 aPLs and older age at SLE diagnosis were the individually factors with highest hazard ratios for new TE when adjusting for sex, ethnic ancestry and age. Figure 1. Figure 2. Conclusions This population-level study reveals a heightened risk of TE, particularly in the context of APS, around SLE onset. The elevated thromboembolic risk in new SLE requires attention and may call for preventive measures.