Non-criteria manifestations in primary antiphospholipid syndrome: a French multicenter retrospective cohort study

Background From this retrospective study, we aimed to (1) describe the prevalence and characteristics of non-criteria features in primary antiphospholipid syndrome (p-APS) and (2) determine their prognostic value. Methods This retrospective French multicenter cohort study included all patients diagnosed with p-APS (Sydney criteria) between January 2012 and January 2019. We used Kaplan-Meier and adjusted Cox proportional hazards models to compare the incidence of relapse in p-APS with and without non-criteria manifestations. Results One hundred and seventy-nine patients with p-APS were included during the study time, with a median age of 52.50 years [39.0; 65.25] and mainly women ( n = 112; 62.6%). Among them, forty-three patients (24.0%) presented at least one non-criteria manifestation during the follow-up: autoimmune cytopenias ( n = 17; 39.5%), Libman Sachs endocarditis ( n = 5; 11.6%), APS nephropathy ( n = 4; 9.3%), livedo reticularis ( n = 8; 18.6%), and neurological manifestations ( n = 12; 27.9%). In comparison to p-APS without any non-criteria manifestations ( n = 136), p-APS with non-criteria features had more arterial thrombosis ( n = 24; 55.8% vs n = 48; 35.3%; p = 0.027) and more frequent pre-eclampsia ( n = 6; 14.3% vs n = 4; 3.1%; p = 0.02). The prevalence of triple positivity was significantly increased in patients with non-criteria features ( n = 20; 47.6% vs n = 25; 19.8%; p = 0.001). Patients with p-APS and non-criteria manifestations ( n = 43) received significantly more additional therapies combined with vitamin K antagonists and/or antiaggregants. Catastrophic APS (CAPS) tended to be more frequent in p-APS with non-criteria features ( n = 2; 5.1% vs none; p = 0.074). The p-APS with non-criteria manifestations had significantly increased rates of relapse ( n = 20; 58.8% vs 33; 33.7%; p = 0.018) in bivariate analysis, but in survival analyses, the hazard ratio (HR) of relapse was not significantly different between the two groups (HR at 1.34 [0.67; 2.68]; p = 0.40). Conclusions The presence of non-criteria features is important to consider, as they are associated with particular clinical and laboratory profiles, increased risk of relapse, and need for additional therapies. Prospective studies are necessary to better stratify the prognosis and the management of p-APS.