Loss of antiphospholipid antibody positivity decreases the risk of recurrent thrombosis in thrombotic antiphospholipid syndrome.

Abstract

To establish the predictive value of antiphospholipid antibody (aPL) negativization on recurrent thrombosis in thrombotic antiphospholipid syndrome (APS). Retrospective cohort study including all consecutive adult patients with APS followed at Hospital de Santa Maria, Lisbon, Portugal, up to December 2024. At diagnosis, all patients were positive for solid-phase aPL. Then, patients were categorized in two groups according to aPL during follow-up: (i) persistently aPL-positive; (ii) aPL-negativization defined as previous aPL-positive and current aPL-negative (two consecutive times, ≥12 months apart). Outcomes included recurrent thrombosis under antithrombotic therapy. Predictors of aPL-negativization and recurrent thrombosis were assessed using Cox regression analysis. Of the 116 included patients (female, 78.4%; primary APS, 72.1%; triple positivity, 40.5%), totalling 1084 patient years (PY), 31.9% became aPL-negative (3.4 events/100PY). The follow-up time was similar between aPL-positive and aPL-negativization groups (P = 0.681), and before and after aPL-negativization (P = 0.072). At diagnosis, triple aPL-positivity predicted against aPL-negativization, while primary APS predicted aPL-negativization. Forty-five patients (38.8%) experienced 68 recurrences (4.2 events/100PY). Age at APS onset, arterial thrombosis and persistent triple aPL-positivity predicted recurrence. Globally, aPL-negativization did not predict recurrence (HR 0.58, 95%CI 0.29-1.14). Among patients who became aPL-negative, the cumulative incidence of recurrent thrombosis did not differ before aPL-negativization (HR 0.52, 95%CI 0.26-1.06) but dropped by 88% after aPL-negativization (HR 0.12, 95%CI 0.05-0.58), even after adjusting for age, primary APS and type of initial thrombosis (P = 0.006). The risk of recurrent thrombosis drops significantly after aPL-negativization, highlighting the utility of serial aPL monitoring in clinical practice.