Thrombotic recurrence after anticoagulation cessation in patients with antiphospholipid syndrome and antiphospholipid antibody negativization: a systematic review and meta-analysis

BACKGROUND: Antiphospholipid syndrome (APS) is a thrombotic autoimmune disease, treated with long-term anticoagulation to prevent thrombotic complications. APS is defined by persistent presence of antiphospholipid antibodies (aPLs). However, certain patients lose aPL positivity over time. The risk of thrombotic recurrence after aPL negativization is unknown; hence, the necessity of continued anticoagulation in this subset of patients is uncertain. OBJECTIVES: To assess thrombotic recurrence in patients with APS and aPL negativization after discontinuation of anticoagulation. METHODS: In this systematic review and meta-analysis, Pubmed, Embase, Web of Science, Cochrane Library, Emcare, and Academic Search Premier were searched for studies including patients with APS, aPL negativization and discontinued anticoagulation. Risk of bias was assessed using the Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool. The primary outcome was the pooled incidence rate (95% CI) for thrombotic recurrence after discontinuation of anticoagulation, estimated using a random-effects Poisson regression model. RESULTS: In total, 55 patients from 6 relevant observational cohort studies fulfilled the inclusion criteria. Heterogeneity among these studies was found in the definition of aPL negativization, timing of treatment discontinuation and follow-up. A total of 3 venous thrombotic recurrences were reported, resulting in a pooled thrombotic recurrence rate of 1.61 per 100 person-years (95% CI: 0.52-4.98). CONCLUSIONS: Interpretation of the thrombotic recurrence rate in patients with APS and aPL negativization found in this meta-analysis is limited by the nature and quality of the included data. Future research should assess whether aPL negativiation could be a factor to take into account when re-evaluating the need for long-term anticoagulation in certain low-risk patients with APS.