Accrual of thromboembolic events and antiphospholipid syndrome in new-onset systemic lupus erythematosus: a population-based inception cohort study

Abstract

Objective: This population-based study aimed to determine timing and incidence of arterial and venous thromboembolic events (TE) and antiphospholipid syndrome (APS) relative to systemic lupus erythematosus (SLE) onset and assess relationships between TE, APS and anti-phospholipid antibodies (aPL) during follow-up.

Methods: We included all medical-record confirmed new-onset SLE patients in Southeast Norway (population 2.9 million) 2000-2017 who fulfilled the 2019 European Alliance of Rheumatology Associations/American College of Rheumatology classification criteria. APS was defined by the 2006 Sydney classification criteria, and aPL positivity was determined following international guidelines. Key outcomes were APS, TE and death. We estimated outcome-free survival using Kaplan-Meier methods.

Results: Among 700 new-onset SLE patients followed for a mean of 8 years (SD 5.0), 13% (89/700) experienced a new TE. TE incidence peaked at 59 per 100 person-years (95% CI 38 to 87) in the first year of SLE among aPL positive patients diagnosed with APS, falling to 12 (95% CI 6.2 to 21) in the subsequent 4 years. In patients without APS, corresponding TE incidences were 2.6 (95% CI 1.4 to 4.3) and 0.9 (95% CI 0.5 to 1.4), respectively. The lowest TE incidence was in aPL-negative patients aged <50 years, with 1-year TE-free survival of 0.99 (95% CI 0.97 to 1.0). Beyond the first year, TE-free survival rates did not differ between SLE patients positive and negative for aPL. Standardised mortality rate in patients with and without APS was 4.7 (95% CI 1.8 to 10.7 and 1.7 (95% CI 1.2 to 2.3).

Conclusions: This population-level study reveals high risk of TE, particularly for aPL positive patients around the time of SLE diagnosis. The elevated TE risk requires attention and early preventive strategies in newly diagnosed SLE.

Keywords: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Epidemiology; Systemic Lupus Erythematosus; Thrombosis.

Figure 1. Timing of first thromboembolic event (TE) in new-onset SLE in patients with and without antiphospholipid syndrome (APS). (A) shows the distribution of first TEs in relation to the time of SLE diagnosis, categorised by whether the TE were related to APS (in purple) or not (in green). (B) Shows the temporal occurrence of first TE in new-onset SLE by age at SLE diagnosis; stratified by patients with (B) and without co-occurrence of APS (C). Arterial TEs are shown as circles and venous TEs as diamonds. aPL, antiphospholipid antibodies; APS, antiphospholipid syndrome; SLE, systemic lupus erythematosus.

Figure 2. Risk of developing antiphospholipid syndrome (APS) or thromboembolic events (TEs) in new-onset SLE; stratified by age and aPL status at SLE diagnosis. (A, B) Shows the probability of APS and TE-free survival in new-onset SLE patients with SLE diagnosis under the age of 50 years. (C, D) Shows the probability of APS (C) and TE-free (D) survival in new-onset SLE patients with SLE diagnosis over the age of 50 years. Figures are stratified by aPL status at the time of SLE diagnosis, where positive aPL refers to positive anti-cardiolipin, anti-b2 glycoprotein and/or lupus anticoagulant. aPL, antiphospholipid antibodies; APS, antiphospholipid syndrome; SLE, systemic lupus erythematosus.

Figure 3. Estimated survival in new-onset SLE compared with age-matched and sex-matched controls; stratified by co-occurrence of antiphospholipid syndrome (APS). (A) Illustrates ten-year survival in new-onset SLE with co-occurrence of APS and 15 matched controls by year of birth, sex, geographical origin and residency (striped line). (B) Shows the same in new-onset SLE patients without co-occurrence of APS during their disease course. Patients and controls are included at the time of SLE diagnosis, or if APS diagnosis was later than SLE diagnosis, at the time of APS diagnosis. SLE, systemic lupus erythematosus.