Antiphospholipid antibody trajectories and clinical correlates in an inception cohort of systemic lupus erythematosus

OBJECTIVE: To evaluate longitudinal antiphospholipid antibody (aPL) patterns in newly diagnosed systemic lupus erythematosus (SLE) and their association with vascular events, disease activity and organ damage. METHODS: We conducted a prospective study within the INSPIRE registry including patients with newly diagnosed SLE (median disease duration 232 days [114-484]) with serum at baseline, 6 and 24 months. Anti-cardiolipin (aCL) and anti-beta2 glycoprotein I (anti-β2GPI) IgG/IgM were measured by ELISA; lupus anticoagulant when feasible. aPL positivity was analysed using manufacturer cut-offs and moderate-high titres (>40 U). Patients were classified as persistently negative, positive, fluctuating or negativised. High- and low-risk aPL profiles were defined per EULAR recommendations. Associations with thrombosis, SLEDAI-2K, Physician Global Assessment (PGA) and SLICC/ACR Damage Index (SDI) were assessed. RESULTS: Among 270 patients, 77.1% were aPL-positive at least once, predominantly low-titre. Moderate-high titre aPLs were less frequent and stable. Most patients with baseline negativity or low-titre/single positivity reverted to negative, whereas dual or triple positivity was associated with persistence. A subgroup (3.1%) progressed from negative/low-titre to high-risk profiles. aPL negativisation occurred in 12.5% and was inversely associated with baseline aPL burden. Over two years, 19 (7%) developed thrombosis, with higher risk in high-risk and persistently positive groups; no thrombotic events occurred in persistently aPL-negative patients.aPL titres did not correlate with SLEDAI-2K or PGA, while aCL IgG and anti-β2GPI IgG correlated weakly with anti-dsDNA. SDI remained low across groups. CONCLUSION: In early SLE, aPLs are largely low-titre and fluctuating, with some patients evolving to higher-risk states, supporting serial aPL testing.