POS0767 CLINICAL MANIFESTATIONS, TREATMENT, AND OUTCOMES OF “NON-CRITERIA” ANTIPHOSPHOLIPID SYNDROME IN COMPARISON WITH DEFINITE ANTIPHOSPHOLIPID SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: G. Pires Da Rosa, E. Ferreira, B. Sousa-Pinto, I. Rodriguez-Pubto, P. Bettencourt, R. Cervera, G. Espinosa
Journal: Annals of the Rheumatic Diseases (2021)

Background: Patients with laboratorial or clinical manifestations suggestive of antiphospholipid syndrome (APS) but not fulfilling the classification criteria [1] constitute a challenge in clinical practice. Objectives: To establish a comparison between patients with “non-criteria” versus those with definite APS on the frequency of clinical manifestations, prescribed therapies and reported outcomes. Methods: A systematic review of observational studies comparing “non-criteria” with definite APS patients was performed searching 4 electronic databases. Data was extracted on clinical manifestations, therapies and outcomes. Studies were analyzed globally and, where possible, grouped under four potential “non-criteria” APS subsets. Random-effects meta-analyses were performed. Results: Fourteen studies were included, assessing a total of 3,238 participants (Table 1). In the meta-analysis, no difference was detected in the frequency of arterial events or thrombosis recurrence between “non-criteria” and definite APS. However, a lower frequency of venous events was observed in “non-criteria” patients (risk ratio [RR]=0.9; 95%CI 0.7-1.0; p-value=0.047, I 2 =0%; Q Cochran p-value=0.226). Regarding obstetric morbidity, no difference was observed in most outcomes, but previous history of intrauterine growth restriction was less frequent (RR=0.7; 95%CI=0.6-0.9; p-value=0.003, I 2 =0%; Q Cochran p-value=0.228) and the risk of prematurity in followed pregnancies lower in “non-criteria” patients. There was no significant difference in treatment frequency between groups, except for less use of hydroxychloroquine in “non-criteria” APS (RR=0.7; 95%CI=0.5-0.9; p-value=0.007, I 2 =46.5%; Q Cochran p-value=0.642). There was no significant difference in the risk of fetal loss between groups either with or without treatment (Figure 1). It should be noted that significant heterogeneity was observed in some outcomes across the studied categories. Most studies focused on “seronegative” and “incomplete laboratory” APS. Table 1. Description of studies included in the systematic review. Author, year (reference ) Number of Patients Definite APS NC-APS (global ) Mekinian, 2012 [2] 25 53 Rodriguez-Garcia, 2012 [3] 87 67 Conti, 2014 [4] 25 24 Ofer-Shiber, 2015 [5] 126 117 Mekinian, 2016 [6] 83 96 Omar, 2018 [7] 30 30 Signorelli, 2017 [8] 77 13 Fredi, 2018 [9] 85 81 Litvinova, 2018 [10] 41 17 Alijotas-Reig, 2019 [11] 1000 640 Ferreira, 2020 [12] 15 21 Liu, 2020 [13] 192 90 Li, 2020 [14] 34 94 Lo, 2020 [15] 12 24 Abbreviations – APS: Antiphospholipid Syndrome; NC-APS: Non-criteria antiphospholipid syndrome. Conclusion: This review suggests an absence of marked differences in most of the evaluated variables regarding clinical manifestations, treatment and outcomes between “non-criteria” and definite APS. These results should be interpreted with caution in light of the low-quality evidence available and heterogeneity observed in some outcomes. References: [1]S Miyakis et al., J Thromb Haemost 4 (2), 295 (2006). [2]A Mekinian et al., Journal of Reproductive Immunology 94 (2), 222 (2012). [3]JL Rodriguez-Garcia et al., Ann Rheum Dis 71 (2), 242 (2012). [4]F Conti et al., J Immunol Res 2014 , 389601 (2014). [5]S Ofer-Shiber and Y Molad, Blood Coagul Fibrinolysis 26 (3), 261 (2015). [6]A Mekinian et al., Semin Arthritis Rheum 46 (2), 232 (2016). [7]G Omar et al., Egyptian Rheumatologist 40 (2), 111 (2018). [8]F Signorelli et al., Annals of the Rheumatic Diseases 76 , 887 (2017). [9]M Fredi et al., Front Immunol 9 , 864 (2018). [10]E Litvinova et al., Front Immunol 9 , 2971 (2018). [11]J Alijotas-Reig et al., Rheumatology (Oxford) (2019). [12]TG Ferreira et al., Clin Rheumatol 39 (4), 1167 (2020). [13]T Liu et al., Arthritis Res Ther 22 (1), 33 (2020). [14]X Li et al., Clinical Rheumatology (2020). [15]HW Lo et al., Eur J Obstet Gynecol Reprod Biol 244 , 205 (2020). Figure 1. Forest plot of studies included in the meta-analysis regarding pregnancy and treatment outcomes. Acknowledgements: The authors wish to thank Helena Donato, from the Documentation Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal, for her assistance performing the search for the systematic review. Disclosure of Interests: None declared